The first dog-origin porcine circovirus type 4 complete genomic sequence have high homology with that of pig-derived strains.

Introduction: Porcine circovirus 4 (PCV4) was discovered in 2019 and then proved to be pathogenic to piglets. Nevertheless, few studies were currently available about PCV4 infection in species other than pigs and there is no information about the prevalence of PCV4 in dogs. Methods: To fill this gap, 264 dog samples were collected from animal hospitals in the Southwest of China from 2021 to 2022 and screened for PCV4. Moreover, the complete genome of one PCV4 strain (SCABTC-Dog2022) were obtained successfully and shared a high identity (97.9-99.0%) with other PCV4 strains derived from pigs, dairy cows, raccoon dogs and foxes. The SCABTC-Dog2022 were analyzed together with 51 reference sequences. Results and Discussion: The detected results showed a low percentage of PCV-4 DNA (1.14%, 3/264), indicating that PCV4 could be identified in dogs in southwest China. Phylogenetic tree showed that SCABTC-Dog2022 strain derived from dog were clustered in a closed relative and geographically coherent branch with other PCV4 strains collected from four provinces (Sichuan, Fujian, Hunan and Inner Mongolia) of China. To our knowledge, it is the first detection of PCV4 in dogs globally. The association between PCV4 status and clinical syndromes in dogs deserves additional investigations.

Cembranoids and their bioactivities in soft coral Sarcophyton glaucum / 中国中药杂志

Chemical constituents in soft coral Sarcophyton glaucum were separated and purified by various chromatographic methods. Based on the spectral data, physicochemical properties, and comparison with the data reported in the literature, nine cembranoids, including a new cembranoid named sefsarcophinolide(1) together with eight known cembranoids, namely(+)-isosarcophine(2), sarcomilitatin D(3), sarcophytonolide J(4),(1S,3E,7E,13S)-11,12-epoxycembra-3,7,15-triene-13-ol(5), sarcophytonin B(6),(-)-eunicenone(7), lobophytin B(8), and arbolide C(9), were identified. As revealed by biological activity experiment results, compounds 2-6 had weak acetylcholinesterase inhibitory activity, and compound 5 displayed weak cytotoxicity against K562 tumor cell line.

Minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure: a series of 60 cases / 中华外科杂志

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.

MiR-203a-5p Inhibits Multiple Myeloma Cell Proliferation and Cell Cycle Progression via Targeting JAG1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the biological function of miR-203a-5p and the underlying mechanism in multiple myeloma (MM).@*METHODS@#Three miRNA expression profiles (GSE16558, GSE24371 and GSE17498) were downloaded from the GEO database. The three miRNA expression profiles contained 131 MM samples and 17 normal plasmacyte samples. The robust rank aggregation (RRA) method was used to identify the differentially expressed miRNAs between MM and normal plasmacytes. In order to carry out cytological experiments, MM cell line with stable over-expression of miR-203a-5p was constructed with lentivirus. Expression levels of miR-203a-5p in MM cells were quantified by qRT-PCR. The effects of miR-203a-5p on MM cells were investigated using assays of cell viability and cell cycle. Cell proliferation was measured using the Cell Counting kit (CCK)8 assay. The percentage of cells in each cell cycle was measured with a FACSCalibur system. Xenograft tumor models were established to evaluate the role of miR-203a-5p in tumorigenesis in vivo . To elucidate the underlying molecular mechanisms of miR-203a-5p in mediating cell proliferation inhibition and cell cycle arrest in MM, we used TargetScan and miRanda to predict the candidate targets of miR-203a-5p. The potential target of miR-203a-5p in MM cells was explored using the luciferase reporter assay, qRT-PCR, and Western blot.@*RESULTS@#An integrated analysis of three MM miRNA expression datasets showed that the levels of miR-203a-5p in MM were notably downregulated compared with those in normal plasmacytes. Accordingly, the relative expression levels of miR-203a-5p were decreased in MM cell lines. In addition, overexpression of miR-203a-5p inhibited the proliferation and cell cycle progression of RPMI8226 and U266 cells. In vivo experiments demonstrated that upregulation of miR-203a-5p expression could significantly inhibit the tumorigenesis of subcutaneous myeloma xenografts in nude mice. Mechanistic investigation led to the identification of Jagged 1 (JAG1) as a novel and direct downstream target of miR-203a-5p. Interestingly, the reintroduction of JAG1 abrogated miR-203a-5p-induced MM cell growth inhibition and cell cycle arrest.@*CONCLUSION@#Our data demonstrate that miR-203a-5p inhibits cell proliferation and cell cycle progression in MM cells by targeting JAG1, supporting the utility of miR-203a-5p as a novel and potential therapeutic agent for miRNA-based MM therapy.

Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα+) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα+ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the main type of oral cancer. Disturbing DNA repair is an invaluable way to improve the effectiveness of tumor treatment. Here, we aimed to explore the key enhancer drivers associated with DNA damage repair in OSCC cells. METHODS: Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and Kaplan-Meier analysis were applied to explore the relationship among DNA repair-related genes expression and clinical phenotypes based on The Cancer Genome Atlas (TCGA) database. HOMER software and Integrative Genomics Viewer were applied to identify and visualize enhancers using GSE120634. Toolkit for Cistrome Data Browser was applied to predict transcription factors. Human Protein Atlas Database was used to analyze the protein levels of transcription factors in OSCC and control tissues. Seventy-two OSCC patients were included in this study. qRT-PCR was used to detect transcription factor expression in OSCC and adjacent control tissues collected in this study. qRT-PCR and ChIP-qPCR were used to verify the binding of transcription factors to enhancers, and regulation of target genes transcription. Transcription factor knockdown and control cells were treated with cisplatin. CCK8 was used to detect cell viability and proliferation. Western blotting was implemented to detect the levels of DNA repair-related proteins. Transwell assay was used to detect cell invasion. RESULTS: DNA repair was positively associated with the OSCC metastatic phenotype. Patients in the cluster with high expression of DNA repair-related genes had a worse prognosis and a higher proportion of advanced stage, low-differentiation, alcohol consumption and smoking compared to the cluster with low DNA repair-related gene expression. Seventeen metastasis-specific enhancer-controlled upregulated DNA repair-related genes, with the top two upregulated genes being ADRM1 26 S proteasome ubiquitin receptor (ADRM1) and solute carrier family 12 member 7 (SLC12A7) were screened. High mobility group 20 A (HMG20A) was the key prognostic enhancer driver regulating metastasis-specific DNA repair-related genes, with higher expression in OSCC tissues than normal control tissues, and higher expression in metastatic OSCC tissues than non-metastatic OSCC tissues. HMG20A bound to the metastasis-specific enhancers of ADRM1 and SLC12A7, thereby promoting ADRM1 and SLC12A7 expression. Knockdown of HMG20A enhanced cisplatin sensitivity of cells, and inhibited OSCC cells from repairing DNA damage caused by cisplatin, as well as proliferation and invasion of OSCC cells. CONCLUSION: HMG20A was identified as the key prognostic enhancer driver regulating DNA repair in OSCC cells, providing a new therapeutic target for OSCC.

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable sterilizing immunity at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 [≤] 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting. Significance statementWe unveiled powerful mucosal neutralization upon BNT162b2 vaccination, mediated by temporary polymeric IgA and explored its longitudinal properties. We present a model, whereby the molecular architecture of polymeric mucosal IgA and its spatial properties are responsible for the outstanding SARS-CoV-2 neutralization potential. We established a methodology for quantitative comparison of immunoreactivity and neutralization for IgG and IgAs in serum and saliva in molar equivalents for standardization in diagnostics, surveillance of protection and for vaccine evaluations.

Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody

Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention. One sentence summaryStructural and functional analyses reveal that a human antibody named VacW-209 confers broad neutralization against SARS-CoV-2 variants including Omicron by recognizing a highly conserved epitope.

Use of the target territory hepatic artery dye-injection method in anatomical hepatectomy / 中华肝胆外科杂志

The clinical data of patients with hepatocellular carcinoma who underwent anatomical hepatectomy at the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from June 2021 to January 2022 were retrospectively analyzed. Of 4 patients, there were 3 males and 1 female, aged (52.0±3.7) years. These patient underwent anatomical hepatectomy using the " target territory hepatic artery dye-injection" method. There were 2 patients with right hemi liver tumors with portal vein tumor thrombus, and 1 patient with a right anterior section tumor which involved the ventral segment of right anterior branch of portal vein. One patient had a left hemi liver tumor with portal vein tumor thrombus. The surgical operations were right hemihepatectomy combined with thrombectomy of portal vein in 2 patients, right anterior sectionectomy in 1 patient, and left hemihepatectomy combined with thrombectomy of portal vein in 1 patient. There were no postoperative complications including bile fistula or bleeding. The "Target territory hepatic artery dye-injection" method could be used in appropriate by selected patients.

Effect of Main Component of Realgar Arsenic Disulfide （As2S2） on DNA Methylation of SKM-1 Cells with Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effects of the main component of Realgar arsenic disulfide （As2S2） on DNA methylation of SKM-1 cells with myelodysplastic syndrome. MethodCell Counting Kit-8 （CCK-8） was used to detect the inhibitory effect of As2S2（0， 1， 2， 4， 8， 16 μmol·L-1）on SKM-1 cells. Propidium iodide （PI） staining was applied to detect the effect of As2S2（0， 1， 2， 4 μmol·L-1）on the SKM-1 cell cycle. The effect of As2S2 （0， 4 μmol·L-1） on the methylation of SKM-1 cells on a genome-wide scale was observed by using Human Methylation 850K BeadChip， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） and gene ontology （GO） analyses. According to the microarray data， the antioncogene TUSC3 was selected， and real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were adopted to investigate the effect of As2S2 （0， 1， 2， 4 μmol·L-1） on the mRNA and protein expression of TUSC3， respectively. ResultCompared with the conditions in the blank group， As2S2 inhibited SKM-1 cells， increased the proportion of cells in the G0/G1 phase， and decreased the proportion of cells in the S phase（P<0.05）. The 850K microarray showed that 4 μmol·L-1 As2S2 could significantly induce DNA methylation in SKM-1 cells， with 12 710 differentially methylated genes involved （50% hypermethylated and 50% hypomethylated genes）. KEGG and GO analyses showed that differentially methylated genes were involved in many important biological functions and signaling pathways， including purine metabolism， natural killer cell-mediated cytotoxicity， endocytosis， chemokine signaling pathway， and nuclear ubiquitin ligase complex. In terms of downstream gene expression， Real-time PCR and Western blot showed that As2S2 increased the expression of TUSC3， as compared with the conditions in the blank group （P<0.05）. ConclusionAs2S2， the main component of Realgar， has a significant regulatory effect on the methylation of SKM-1 cells， which is presumedly achieved by increasing the expression of TUSC3.

Metabolomics based protective effect of Amygdalus mongolica on pulmonary fibrosis in rats / 药学学报

This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica. The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) and Masson staining, the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were detected, and transforming growth factor β1 (TGF-β1), Smad family member 3 (Smad3), α-smooth muscle actin (α-SMA) pathway index expression in lung tissue was detected by fluorescence quantitative PCR. UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them. The results showed that compared with the model group, the medium (1.5 g·kg-1) and high (3.0 g·kg-1) doses of Amygdalus mongolica total extract could significantly reduce the lung index, significantly increase the activity of SOD in serum and lung tissue, reduce the degree of alveolar inflammation and pulmonary fibrosis, and reduce MDA in serum and lung tissue, and significantly reduce TGF-β1, Smad3, α-SMA mRNA expression in lung tissue. Serum metabolomics profile analysis identified 25 significantly different metabolites, the Amygdalus mongolica total extract can participate in linoleic acid metabolism, glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers: lysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z)), lysoPC(20∶0/0∶0), PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0), 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOME), 9,10-dihydroxy-12-octadecenoic acid (9,10-DHOME) to affect pulmonary fibrosis. This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats, and provided a reference basis for the clinical application of Amygdalus mongolica. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No.20170315).

Effect of Bixie deacidification fang on hyperuricemia mouse model and its effect on the expression of renal urate transporter / 药学实践杂志

Objective To investigate the anti-hyperuricemia effects of Bixie deacidification fang on hyperuricemia mice and its mechanism of renal protein transport. Methods The effects of Bixie deacidification fang were investigated on hyperuricemia mice induced by potassium oxonate. Bixie deacidification fang was administered to hyperuricemia mice daily at doses of 220, 440 and 880 mg/kg for 10 days, and allopurinol (5mg/kg) was given as positive control. Serum and urine levels of uric acid and creatinine were determined by colorimetric method. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blot. Results Compared with the model group, high-dose of Bixie deacidification fang inhibited xanthine oxidase (XOD) activities in serum (18.12±1.33 u/L) and that in liver (70.15±5.20 u/g protein) (P<0.05), decrease levels of serum uric acid (2.04 ± 0.64mg/L) (P<0.05) and serum creatinine (0.35±0.18µmol/L) and blood urea nitrogen (BUN)(8.83±0.71mmol/L) (P<0.05), ncreased levels of urine uric acid (38.34±8.23mg/L), urine creatinine (34.38±1.98mmol/L), down-regulated of URAT1 and up-regulated of OAT1 protein expressions (P<0.05) in the renal tissue of hyperuricemia mice. Conclusion Bixie deacidification fang recipe may promote the excretion of uric acid in the kidney by up-regulating the expression of OAT1 protein to promote the excretion of uric acid, and down-regulating the expression of URAT1 protein to inhibit the reabsorption of uric acid.

Thinking and suggestions on pathway management of perioperative enhanced recovery after surgery in gastrointestinal tumors in China / 中华胃肠外科杂志

Enhanced recovery after surgery (ERAS) is a multimodal perioperative care program to decrease the risk of delayed hospitalization, medical complications, readmission and to improve patient short- and long-term outcomes with minimized level of surgical stress responses through multidisciplinary cooperation. Despite its huge success, the program has challenges for further optimization with a primary focus on modification according to the specific pathophysiology and perioperative management characteristics of patients with gastrointestinal tumors to improve the compliance and implementation rate of items. Patient education, prehabilitation, multimodal analgesia, precision surgery, early mobilization, early oral feeding and oral nutrition supplement (ONS) should be regarded as core terms suitable for all the patients. During the application of ERAS pathway management, it is necessary to fully understand the perioperative changes of organ function and pathophysiology, and to strictly implement the ERAS program and items based on evidence-based medicine. Moreover, the close collaboration of multidisciplinary teams is needed to improve the compliance and increase the adherence rate of ERAS protocol for patients, which emphasizes the dynamic, gap-free and whole course management that covers pre-hospital, pre-operative, intra-operative, post-operative and post-hospital periods. Concurrently, we encourage our patients and their families to participate in the whole healthcare activities. Even more concerning, it is indispensable to adjust ERAS program for special time and special patients. At present, several consensus and guidelines on the ERAS management of gastrointestinal tumor surgery have come out for clinical practice in China, which, however, still lacks a high-level evidence from more high-quality clinical trials conducted by Chinese researchers. It is urgent to carry out a series of large-scale randomized controlled studies in accordance with international standards to obtain high-level evidence-based medical evidence for clinical practice, which is problem-oriented and integrated with features of metabolism and perioperative management of gastrointestinal tumor surgery.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells.

BACKGROUND: The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. METHODS: Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. RESULTS: Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. CONCLUSIONS: CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.

Cell fusion in cancer hallmarks: Current research status and future indications.

Cell fusion is involved in several physiological processes, such as reproduction, development and immunity. Although cell fusion in tumors was reported 130 years ago, it has recently attracted great interest, with recent progress in tumorigenesis research. However, the role of cell fusion in tumor progression remains unclear. The pattern of cell fusion and its role under physiological conditions are the basis for our understanding of the pathological role of cell fusion. However, the role of cell fusion in tumors and its functions are complicated. Cell fusion can directly increase tumor heterogeneity by forming polyploids or aneuploidies. Several studies have reported that cell fusion is associated with tumorigenesis, metastasis, recurrence, drug resistance and the formation of cancer stem cells. Given the diverse roles cell fusion plays in different tumor phenotypes, methods based on targeted cell fusion have been designed to treat tumors. Research on cell fusion in tumors may provide novel ideas for further treatment.

Growth factors contribute to the mediation of angiogenic capacity of glioma-associated mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are important components of stromal cell populations and serve a crucial role in tumor growth and progression. Previously, our laboratory successfully isolated and cultured MSCs from human glioma issues and demonstrated that glioma-associated mesenchymal stem cells (gb-MSCs) participate in and maintain tumor angiogenesis. Furthermore, growth factors, such as fibroblast growth factor and vascular endothelial cell growth factor, were demonstrated to be associated with endothelial cell tube formation. However, the effect of transforming growth factor ß1 (TGF-ß1) and platelet-derived growth factor-BB (PDGF-BB) on the angiogenic activity of gb-MSCs remains unknown. The present study aimed therefore to explore their effects in gb-MSCs angiogenesis. In the present study, gb-MSCs were isolated from patients with glioma and were characterized using flow cytometry and differentiation experiments. Furthermore, the results from tube formation assay revealed that TGF-ß1 and PDGF-BB could mediate the angiogenic capacity of gb-MSCs in vitro. In addition, results from immunofluorescence demonstrated that gb-MSCs expressed TGF-ß1R and PDGFR, which are the receptors for TGF-ß1 and PDGF-BB, respectively. Taken together, these findings indicated that TGF-ß1 and PDGF-BB may serve a crucial role in mediating gb-MSC angiogenesis, which might provide a therapeutic strategy for targeting the angiogenic capacity of gb-MSCs in patients with glioma.

Methodological framework for identifying sustainability intervention priority areas on coastal landscapes and its application in China.

In regional sustainability evaluation and policy analysis, the paradigm of safe operating spaces (SOS) has been widely applied. Yet, SOS is not readily useful for informing policy interventions toward sustainability transition. This study reports on a methodological framework that operationalizes SOS at the regional scale for designing spatially targeted sustainability interventions. In particular, this framework accounts for teleology by integrating policy orientations of the place-variant "major function" of development, and provides early-warnings by integrating long-term social-environmental trends. The framework we proposed has been applied by the Chinese government in a coastal province (Liaoning) for a landscape sustainability project, which is introduced here step-by-step. The four main steps include: (1) Quantifying SOS status across multiple "what to sustain" dimensions, e.g., land scarcity, water scarcity, pollutant discharge, and ecosystem health for the inland, and coastal exploitation intensity, marine environmental quality, and marine ecosystem biodiversity for the sea. (2) Quantifying SOS status in terms of the place-variant "what to develop" dimensions, e.g., urbanization-oriented, agriculture-stock-oriented, versus conservation-oriented development. (3) Integrating the two as a composite indicator of three ordinal levels to classify the current SOS status. (4) Developing a multi-level sustainability early-warning system by cross-analysis of the SOS status and social-environmental interaction trends (e.g., changes in, e.g., resource utilization efficiency, pollutant discharge, and eco-environmental quality). The potential use of the framework is demonstrated through the case of Liaoning Province, China, which helps policy-makers to identify priority areas for sustainability interventions. Methodological robustness and future directions of applying this multi-level sustainability early-warning system are further discussed.