Gaps between needs of patient and public involvement and interests of researchers on pancreatic cancer.

OBJECTIVE: Identify whether there were gaps between needs of end-users and interests of researchers focusing on pancreatic cancer. METHODS: A questionnaire for end-users (patients, close family, others) and researchers was developed to measure value from the perspective of different stakeholder groups. Two separate literature analyses were conducted to assess the prevalence and impact of patient and public involvement (PPI). RESULTS: Significant gaps were found between end-users and researchers in valuing basic research (15 vs 25 points, p = 0.005) and treatment (36 vs. 26 points, p = 0.015), but not in early diagnosis, risk factors, or quality of life. PPI was absent from the top 100 cited publications on pancreatic cancer research and was featured in 0.1% of all studies within the field. CONCLUSIONS: Gaps existed between needs of end-users and interests of researchers on basic research and treatment. PPI constituted an insignificant part of the overall pancreatic cancer research literature and had negligible impact in terms of citations. PRACTICAL IMPLICATIONS: To help close the gaps, PPI should be incorporated throughout the research process. The impact of PPI can be enhanced by prestigious journals in consideration of journal policies and encouragements and by dissemination at academic conferences.

Pre-emptive infiltration with betamethasone and ropivacaine for postoperative pain in laminoplasty and laminectomy (PRE-EASE): a prospective randomized controlled trial.

BACKGROUND: Postoperative pain after laminoplasty and laminectomy occurs partially from local trauma of the paraspinal tissue. Finding a multimodal analgesic cocktail to enhance the duration and effect of local infiltration analgesia is crucial. Because of the rapid onset and long duration of action of betamethasone, the authors hypothesized that, a pre-emptive multimodal infiltration regimen of betamethasone and ropivacaine reduces pain scores and opioid demand, and improves patient satisfaction following laminoplasty and laminectomy. MATERIALS AND METHODS: This prospective, randomized, open-label, blinded endpoint study was conducted between 1 September 2021 and 3 June 2022, and included patients between the ages of 18 and 64 scheduled for elective laminoplasty or laminectomy under general anesthesia, with American Society of Anesthesiologists classification I/II. One hundred sixteen patients were randomly assigned to either the BR (Betamethasone-Ropivacaine) group or the R (Ropivacaine) group in a 1:1 ratio. Each group received pre-emptive infiltration of a total of 10 ml study solution into each level. Every 30 ml of study solution composed of 0.5 ml of betamethasone plus 14.5 ml of saline and 15 ml of 1% ropivacaine for the BR group, and 15 ml of 1% ropivacaine added to 15 ml of saline for the R group. Infiltration of epidural space and intrathecal space were avoided and the spinous process, transverse process, facet joints, and lamina were injected, along with paravertebral muscles and subcutaneous tissue. Cumulative 48 h postoperative butorphanol consumption via PCA (Patient-controlled analgesia) was the primary outcome. Intention-to-treat (ITT) principle was used for primary analysis. RESULTS: Baseline characteristics were identical in both groups ( P >0.05). The cumulative 48 h postoperative butorphanol consumption via PCA was 3.0±1.4 mg in the BR group ( n =58), and 7.1±1.2 mg in the R group ( n =58) ( P <0.001). Overall cumulative opioid demand was lower at different time intervals in the BR group ( P <0.001), along with the estimated median time of first analgesia demand via PCA (3.3 h in the BR group and 1.6 h in the R group). The visual analog scale (VAS) score at movement and rest were also significantly lower until 3 months and 6 weeks, respectively. No side effects or adverse events associated with the intervention were observed in this study. CONCLUSIONS: Pre-emptive analgesia with betamethasone and ropivacaine provides better postoperative pain management following laminoplasty and laminectomy, compared to ropivacaine alone. This is an effective technique worthy of further evaluation.

Opioid-Sparing Effects of Flurbiprofen Axetil as an Adjuvant to Ropivacaine in Pre-Emptive Scalp Infiltration for Post-Craniotomy Pain: Study Protocol for a Multicenter, Randomized Controlled Trial.

Background: Pain after craniotomy remains a poorly controlled problem that is mainly caused by the inflammatory reaction at the incision site. Nowadays, systemic opioids use, as first-line analgesics, is often limited because of adverse effects. Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug merged into emulsified lipid microspheres, which represent a strong affinity to inflammatory lesions. Local administration of flurbiprofen into a surgical wound has induced enhanced analgesic efficacy and few systemic or local adverse effects after oral surgery. However, the impact of local FA, as a non-opioid pharmacologic alternative, remains elusive on postoperative pain in craniotomy. In this study, we presume that pre-emptive infiltration of scalp with FA as an adjuvant to ropivacaine can lead to less sufentanil consumption postoperatively in patient controlled intravenous analgesia (PCIA) compared with ropivacaine alone. Methods/Design: We design a multicenter, randomized controlled study that will enroll 216 subjects who are planned to receive supratentorial craniotomy. Patients will receive pre-emptive infiltration of scalp either with 50 mg FA and 0.5% ropivacaine, or with 0.5% ropivacaine alone. Primary outcome is total consumption of sufentanil with PCIA device at 48 h postoperatively. Discussion: This is the first study attempting to explore the analgesic and safety profile of local FA as an adjuvant to ropivacaine for incisional pain in patients undergoing craniotomy. It will provide additional insights into the opioid-sparing analgesia pathways by local administration of NSAIDs for neurosurgery.

Lidocaine aerosol sprayed on oral and/or nasal mucosa for the rescue of acute trigeminal neuralgia exacerbations: A retrospective study.

INTRODUCTION: Acute trigeminal neuralgia exacerbation is a common reason for frequent emergency department visits, that often occurs while waiting for surgery, but evidence on effective drugs for acute trigeminal neuralgia is scant. Whether lidocaine aerosol could be a rescue option for the treatment of acute trigeminal neuralgia exacerbations is worth exploring. Positive predictors of the analgesic effects of lidocaine aerosol also warrant further investigation. METHODS: This is a retrospective study with a total of 152 patients. We analyzed the efficacy of lidocaine aerosol for the treatment of acute trigeminal neuralgia exacerbations. A positive response was considered a decrease in the VAS score of at least 50% at 30 min of treatment. Multivariable logistic analyses were performed to identify predictive factors for lidocaine aerosol response. RESULTS: In the group of 109 responders, the VAS score decreased from 8.3 ± 1.1 cm to 0.8 ± 1.0 cm at 15 min, and 1.7 ± 1.0 cm at 30 min. The effective rate at 15 min and 30 min were 77.6% and 70.4%, respectively. Multivariate logistic analyses showed the treatment may provide better clinical outcomes in V2 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.15, p < 0.001), V3 trigeminal neuralgia (OR 0.02, 95%Cl 0.001-0.16, p = 0.001), and V2 + V3 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.13, p < 0.001), patients who were taking carbamazepine or oxcarbazepine with a maximum dose (OR 6.15, 95%Cl 2.11-17.93, p = 0.001) were less likely to experience immediate pain relief. CONCLUSION: Lidocaine aerosol sprayed on oral and/or nasal mucosa is beneficial for immediate pain relief in patients with acute trigeminal neuralgia exacerbations. It is expected to become a promising treatment option for patients with V2 and/or V3 trigeminal neuralgia.

Analysis of factors that influence the occurrence of otitis media with effusion in pediatric patients with adenoid hypertrophy.

Objective: Adenoid hypertrophy (AH) and otitis media with effusion (OME) are common pediatric otolaryngological diseases and often occur concurrently. The purpose of this study was to comprehensively analyze the factors that influence the occurrence of OME pediatric patients with AH. Methods: Patients younger than 12 years with AH, who were hospitalized for treatment at Beijing Tsinghua Changgung Hospital in Beijing, China, between March 2018 and February 2022 were enrolled. The patients were divided into an AH group and an AH + OME group based on the presence of OME. The authors collected the following clinical data for univariable analysis: sex; age; body mass index (BMI); comorbid nasal congestion/rhinorrhea, recurrent tonsillitis, or allergic rhinitis (AR); adenoid and tonsil grade; tonsillar hypertrophy; food/drug allergy; history of adenoidectomy and congenital diseases; breastfeeding status; preterm birth; exposure to environmental tobacco smoke (ETS); family history of adenotonsillectomy, otitis media, and AR; main data of polysomnography and oropharyngeal conditional pathogen culture data of some patients. Univariate analysis was performed as a basis for logistic regression analysis. Results: A total of 511 children (329 boys and 182 girls) were included, their mean age was 5.37 ± 2.10 years. Of them, 407 (79.6%) were in the AH group and 104 (20.4%) in the AH + OME group. Univariate analysis revealed statistically significant differences in age, BMI, adenoid grade, AR, breastfeeding status, and ETS exposure between the two groups. Multivariate stepwise logistic regression analysis showed that age, adenoid grade, AR, breastfeeding status, and ETS influenced the occurrence of OME in pediatric patients with AH. The risk of OME decreased with increasing age. High adenoid grade, ETS exposure, and comorbid AR were risk factors for OME in pediatric patients with AH, but breastfeeding was a protective factor. The final analytical results of the oropharyngeal conditional pathogen culture data showed that Streptococcus pneumoniae positivity was associated with OME in AH. Conclusion: The pathogenesis of AH with OME is complex. Young age, high adenoid grade, ETS exposure, non-breastfed status, comorbid AR, and the presence of S. pneumoniae in the oropharynx are risk factors for OME in pediatric patients with AH.

Screening Biomarkers of Sudden Coronary Death Based on mRNA Expression Profile of Rat Myocardial Tissues.

OBJECTIVES: To explore the differential expression of messenger RNA (mRNA) in myocardial tissues of rats with sudden coronary death (SCD), and to provide ideas for the forensic identification of SCD. METHODS: The rat SCD model was established, and the transcriptome sequencing was performed by next-generation sequencing technology. Differentially expressed genes (DEGs) in myocardial tissues of SCD rats were screened by using the R package limma. A protein-protein interaction (PPI) network was constructed by using the STRING database and Cytoscape 3.8.2 on DEG, and hub genes were screened based on cytoHubba plug-in. Finally, the R package clusterProfiler was used to analyze the biological function and signal pathway enrichment of the selected DEG. RESULTS: A total of 177 DEGs were associated with SCD and were mainly involved in the renin-angiotensin system and PI3K-Akt signaling pathway. The genes including angiotensinogen (AGT), complement component 4a (C4a), Fos proto-oncogene (FOS) and others played key roles in the development of SCD. CONCLUSIONS: Genes such as AGT, C4a, FOS and other genes are expected to be potential biomarkers for forensic identification of SCD. The study based on mRNA expression profile can provide a reference for forensic identification of SCD.

In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma.

TIPE1 is a gene in the TNFAIP8 family involved in immune regulation and tumorigenesis. Although previous studies demonstrated that TIPE1 might play different roles in different tumors, its expression and role in lymphoma are unclear. Here we observed TIPE1 expression in diffuse large B cell lymphoma (DLBCL). Two microarrays containing 96 tumor tissue specimens were obtained from the Affiliated Hospital of Nantong University biobank. All specimens came from patients with a clear pathological diagnosis of lymphoma, lymphadenitis, breast cancer, or bladder cancer, and we performed immunohistochemical experiments on these tissue specimens. GEPIA and TIMER platforms were used for bioinformatic analyses. We found higher TIPE1 expression in tumor tissues from patients with lymphoma compared with those with lymphadenitis, breast cancer, or bladder cancer. The GEPIA and TIMER analyses revealed that TIPE1 was upregulated in DLBCL tissues but not in invasive breast carcinoma, urothelial bladder carcinoma, or liver hepatocellular carcinoma tissues. TIPE1 expression was irrelevant for pathological stage, overall survival, or DLBCL immune infiltration levels. However, TIPE1 expression was correlated with MKI67 expression in DLBCL. Overall, TIPE1's high expression levels in DLBCL may contribute to tumor growth in DLBCL.

[Analysis of the salt-stress responsive element of the promoter of peanut small GTP binding protein gene AhRabG3f].

To study the molecular mechanism of salt stress response of peanut small GTP binding protein gene AhRabG3f, a 1 914 bp promoter fragment upstream of the start codon of AhRabG3f gene (3f-P) from peanut was cloned. Subsequently, five truncated fragments (3f-P1-3f-P5) with lengths of 1 729, 1 379, 666, 510 and 179 bp were obtained through deletion at the 5' end, respectively. Plant expression vectors where these six promoter fragments were fused with the gus gene were constructed and transformed into tobacco by Agrobacterium-mediated method, respectively. GUS expression in transgenic tobacco and activity analysis were conducted. The gus gene expression can be detected in the transgenic tobacco harboring each promoter segment, among which the driving activity of the full-length promoter 3f-P was the weakest, while the driving activity of the promoter segment 3f-P3 was the strongest. Upon exposure of the transgenic tobacco to salt stress, the GUS activity driven by 3f-P, 3f-P1, 3f-P2 and 3f-P3 was 3.3, 1.2, 1.9 and 1.2 times compared to that of the transgenic plants without salt treatment. This suggests that the AhRabG3f promoter was salt-inducible and there might be positive regulatory elements between 3f-P and 3f-P3 in response to salt stress. The results of GUS activity driven by promoter fragments after salt treatment showed that elements included MYB and GT1 between 1 930 bp and 1 745 bp. Moreover, a TC-rich repeat between 682 bp and 526 bp might be positive cis-elements responsible for salt stress, and an MYC element between 1 395 bp and 682 bp might be a negative cis-element responsible for salt stress. This study may facilitate using the induced promoter to regulate the salt resistance of peanut.

Computational Drug Repositioning and Experimental Validation of Ivermectin in Treatment of Gastric Cancer.

Objective: The aim of the present study was repositioning of ivermectin in treatment of gastric cancer (GC) by computational prediction based on gene expression profiles of human and mouse model of GC and validations with in silico, in vitro and in vivo approaches. Methods: Computational drug repositioning was performed using connectivity map (cMap) and data/pathway mining with the Ingenuity Knowledge Base. Tissue samples of GC were collected from 16 patients and 57 mice for gene expression profiling. Additional seven independent datasets of gene expression of human GC from the TCGA database were used for validation. In silico testing was performed by constructing interaction networks of ivermectin and the downstream effects in targeted signaling pathways. In vitro testing was carried out in human GC cell lines (MKN74 and KATO-III). In vivo testing was performed in a transgenic mouse model of GC (INS-GAS mice). Results: GC gene expression "signature" and data/pathway mining but not cMAP revealed nine molecular targets of ivermectin in both human and mouse GC associated with WNT/ß-catenin signaling as well as cell proliferation pathways. In silico inhibition of the targets of ivermectin and concomitant activation of ivermectin led to the inhibition of WNT/ß-catenin signaling pathway in "dose-depended" manner. In vitro, ivermectin inhibited cell proliferation in time- and concentration-depended manners, and cells were arrested in the G1 phase at IC50 and shifted to S phase arrest at >IC50. In vivo, ivermectin reduced the tumor size which was associated with inactivation of WNT/ß-catenin signaling and cell proliferation pathways and activation of cell death signaling pathways. Conclusion: Ivermectin could be recognized as a repositioning candidate in treatment of gastric cancer.

Chemopreventive Effects of Dietary Isothiocyanates in Animal Models of Gastric Cancer and Synergistic Anticancer Effects With Cisplatin in Human Gastric Cancer Cells.

Naturally occurring isothiocyanates (ITCs) from edible vegetables have shown potential as chemopreventive agents against several types of cancer. The aims of the present study were to study the potential of ITCs in chemoprevention and in potentiating the efficacy of cytotoxic drugs in gastric cancer treatment. The chemoprevention was studied in chemically induced mouse model of gastric cancer, namely N-methyl-N-nitrosourea (MNU) in drinking water, and in a genetically engineered mouse model of gastric cancer (the so-called INS-GAS mice). The pharmacological effects of ITCs with or without cisplatin were studied in human gastric cell lines MKN45, AGS, MKN74 and KATO-III, which were derived from either intestinal or diffused types of gastric carcinoma. The results showed that dietary phenethyl isothiocyanate (PEITC) reduced the tumor size when PEITC was given simultaneously with MNU, but neither when administrated after MNU nor in INS-GAS mice. Treatments of gastric cancer cells with ITCs resulted in a time- and concentration-dependent inhibition on cell proliferation. Pretreatment of gastric cancer cells with ITCs enhanced the inhibitory effects of cisplatin (but not 5-fluorouracil) in time- and concentration-dependent manners. Treatments of gastric cancer cells with PEITC plus cisplatin simultaneously at different concentrations of either PEITC or cisplatin exhibited neither additive nor synergetic inhibitory effect. Furthermore, PEITC depleted glutathione and induced G2/M cell cycle arrest in gastric cancer cells. In conclusion, the results of the present study showed that PEITC displayed anti-cancer effects, particularly when given before the tumor initiation, suggesting a chemopreventive effect in gastric cancer, and that pretreatment of PEITC potentiated the anti-cancer effects of cisplatin, possibly by reducing the intracellular pool of glutathione, suggesting a possible combination strategy of chemotherapy with pretreatment with PEITC.

Pre-Emptive Incision-Site Infiltration with Ropivacaine Plus Dexamethasone for Postoperative Pain After Supratentorial Craniotomy: A Prospective Randomized Controlled Trial.

BACKGROUND: Incision-site infiltration with local anesthetics prevents pain on incision site, but pain relief is limited to the first few postoperative hours. Dexamethasone as an adjuvant to local infiltration successfully achieves better postoperative pain relief; however, this has not been studied in craniotomy patients yet. STUDY DESIGN AND METHODS: This is a prospective, single-center, blinded, randomized, controlled trial included patients aged between 18 and 64 years, ASA physical status of I-II, scheduled for elective supratentorial tumor craniotomy under general anesthesia. We screened patients for enrollment from April 4, 2019 through August 15, 2019. The final study visit of the last patient was conducted on February 13, 2020. We randomly assigned eligible participants (1:1) to either the dexamethasone group who received incision-site infiltration of 0.5% ropivacaine plus 0.033% dexamethasone (N=70) or the control group who received 0.5% ropivacaine alone (N=70). Primary outcome was the cumulative sufentanil consumption (µg) within 48 hours postoperatively. Primary analysis was performed based on the modified intention-to-treat (MITT) principle. RESULTS: Baseline characteristics were similar between the groups (p>0.05). Sufentanil consumption during the first 48 hours postoperatively was 29.0 (10.7) µg in the dexamethasone group and 38.3 (13.7) µg in the control group (mean difference -9.3, 95% CI -13.4 to -5.1; p<0.001). There was no serious adverse effect directly associated with incision-site infiltration or local dexamethasone use. CONCLUSION: The addition of dexamethasone to pre-emptive incision-site infiltration with the local anesthetic can reduce about 27% of opioids consumption and the postoperative pain scores within 72 hours after craniotomy. TRIAL REGISTRATION: ClinicalTrials.Gov (NCT03618264).

Neural signaling modulates metabolism of gastric cancer.

Tumors comprise cancer cells and the associated stromal and immune/inflammatory cells, i.e., tumor microenvironment (TME). Here, we identify a metabolic signature of human and mouse model of gastric cancer and show that vagotomy in the mouse model reverses the metabolic reprogramming, reflected by metabolic switch from glutaminolysis to OXPHOS/glycolysis and normalization of the energy metabolism in cancer cells and TME. We next identify and validate SNAP25, mTOR, PDP1/α-KGDH, and glutaminolysis as drug targets and accordingly propose a therapeutic strategy to target the nerve-cancer metabolism. We demonstrate the efficacy of nerve-cancer metabolism therapy by intratumoral injection of BoNT-A (SNAP25 inhibitor) with systemic administration of RAD001 and CPI-613 but not cytotoxic drugs on overall survival in mice and show the feasibility in patients. These findings point to the importance of neural signaling in modulating the tumor metabolism and provide a rational basis for clinical translation of the potential strategy for gastric cancer.

Upregulation of FoxO3a expression through PI3K/Akt pathway attenuates the progression of lupus nephritis in MRL/lpr mice.

FoxO3a plays key roles in inflammation and autoimmunity, and the PI3K-Akt-FoxO3a pathway has been proposed to modulate diverse biological processes. The aim of the present study, using lupus murine models, was to investigate whether FoxO3a contributes to the pathogenesis of lupus nephritis. LY294002 was used as an inhibitor of PI3K/AKT signaling pathway. FoxO3a-targeted small interfering RNA (siRNA) was also used for in vivo intervention. Female MRL/lpr mice were separately injected with LY294002, LY294002+siFoxO3a, and LY294002+siControl for 8 weeks. C57BL/6 mice were normal controls. Disease development, including serum creatinine (CRE), blood urea nitrogen (BUN), proteinuria, and renal pathological changes, was monitored. Levels of anti-dsDNA antibodies and immune complex (IC) deposition in the kidney were also measured. The expression of proteins was evaluated. We found that significant downregulation of FoxO3a was detected in the kidney of MRL/lpr mice as compared with normal control mice. Blockade of p-FoxO3a activation by LY294002 suppressed PI3K/Akt/FoxO3a pathway and the subsequent upregulation of FoxO3a in the nucleus resulting in the severity of inflammation and fibrosis in the kidney of MRL/lpr mice. Also, improved kidney function and decreased circulating anti-dsDNA antibodies were due to the upregulation of FoxO3a. Opposite results were obtained by specific siRNA silencing of Foxo3a in vivo. In conclusion, our research demonstrated that the upregulation of FoxO3a expression through inhibiting PI3K/Akt pathway attenuates murine lupus nephritis (LN). Thus, our results suggest that targeting of FoxO3a can be considered as a novel strategy for the treatment of LN.

Decreased expression of IGFBP6 correlates with poor survival in colorectal cancer patients.

BACKGROUND: The insulin-like growth factor binding protein 6 (IGFBP6), as a specific inhibitor of IGF-Ⅱ, is a candidate human anti-oncogene in multiple tumors. However, the expression of IGFBP6 in colorectal cancer (CRC) and prognostic significance are unclear. METHODS: In this study, we examined colorectal cancer tissues and adjacent normal tissues to determine the expression levels of IGFBP6 mRNA and protein by quantitative reverse-transcription polymerase chain reaction and tissue microarray immunohistochemistry analysis respectively. Moreover, we explored the effects of IGFBP6 on cell growth, migration and invasion by Cell Counting Kit-8(CCK8), colony formation and transwell migration assays. We also investigated whether IGFBP6 expression in tumor tissue correlated with various clinical parameters, including overall survival by univariate and multivariate analyses RESULTS: Both IGFBP6 mRNA and protein levels were significantly lower in colorectal cancer tissues than in adjacent normal colon. Downregulating IGFBP6 using RNAi increased CRC cell proliferation, migration and invasion. Low IGFBP6 expression correlated with poor overall survival in both univariate and multivariate analyses. CONCLUSION: Our data suggest that IGFBP6 may act as a tumor suppressor gene in the development of CRC, and that low IGFBP6 expression could be used as an independent prognostic biomarker in CRC.

Efficacy of Acupuncture Combined with Local Anesthesia in Ischemic Stroke Patients with Carotid Artery Stenting: A Prospective Randomized Trial.

OBJECTIVE: To evaluate the efficacy of electro-acupuncture (EA) or transcutaneous electrical acupoint stimulation (TEAS) on perioperative cerebral blood flow (CBF) and neurological function in ischemic stroke (IS) patients undergoing carotid artery stenting (CAS). METHODS: In total, 124 consecutive IS patients were randomly allocated to the EA, TEAS, and sham groups (groups A, T, and S; 41, 42, and 41 cases, respectively) by software-derived random-number sequence. Groups A and T received EA and TEAS, respectively, at the Shuigou (GV 26) and Baihui (GV 20), Hegu (LI4) and Waiguan (TE 5) acupoints. Group S received sham EA. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the CBF at 30 min after surgery, which was measured by transcranial Doppler sonography. The secondary outcomes included hyperperfusion incidence and neurological function. National Institutes of Health Stroke Scale (NIHSS) and General Evaluation Scale (GES) scores were recorded at 1 week, 1 month, and 3 months postoperatively. RESULTS: Mean CBF velocity at 30 min after surgery in groups A and T was much lower than that in Group S (P < 0.05); the incidence of hyperperfusion in Groups A and T was also lower than that in group S (P <0.05). Acupuncture was an independent factor associated with reduced incidence of hyperperfusion (OR=0.042; 95% CI: 0.002-0.785; =0.034). NIHSS and GES scores improved significantly at 1 week postoperatively in Groups A and T than in Group S (P < 0.05). Relative to Group S, groups A and T exhibited significantly lower incidences of moderate pain, as well as higher incidences of satisfaction with anesthesia, at 1 day postoperatively (P < 0.05). CONCLUSIONS: EA or TEAS administered in combination with local anesthesia during CAS can inhibit transient increases in CBF, reduce the incidence of postoperative hyperperfusion, and improve neurological function. (Registration No. ChiCTR-IOR-15007447).

The growth of a xenograft breast cancer tumor model with engineered hyaluronan-accumulating stroma is dependent on hyaluronan and independent of CD44.

Hyaluronan accumulation in the tumor microenvironment is associated with poor prognosis in several solid human cancers. To understand the role of stromal hyaluronan in tumor progression, we engineered 3T3HAS3, a hyaluronan-producing fibroblast cell line, by lentiviral transduction of Balb/c 3T3 cells with the human hyaluronan synthase 3 (HAS3) gene. 3T3HAS3 cells significantly enhanced tumor growth when co-grafted with MDA-MB-468 cells in nude mice. Immunohistochemical analysis of the xenograft tumors showed that MDA-MB-468 cells were surrounded by hyaluronan-accumulating stroma, closely resembling the morphology observed in human breast cancer specimens. Tumor growth of MDA-MB-468 + 3T3HAS3 co-grafts was greatly reduced upon hyaluronan degradation by lentiviral transduction of a human hyaluronidase gene in 3T3HAS3 cells, or by systemic administration of pegvorhyaluronidase alfa (PEGPH20). In contrast, the growth of the co-graft tumors was not inhibited when CD44 expression was reduced or ablated by small hairpin RNA-mediated CD44 knockdown in MDA-MB-468 cells, CD44 CRISPR knockout in 3T3HAS3 cells, or by grafting these cells in CD44 knockout nude mice. Collectively, these data demonstrate that tumor growth of an engineered xenograft breast cancer model with hyaluronan-accumulating stroma can be dependent on hyaluronan and independent of CD44.

Pre-emptive scalp infiltration with dexamethasone plus ropivacaine for postoperative pain after craniotomy: a protocol for a prospective, randomized controlled trial.

Background: Approximately 55-87% of the patients undergoing craniotomy experience moderate to severe pain during the first 48 hrs after surgery, which negatively influences patients' postoperative rehabilitation. Recently, local infiltration of analgesia (LIA) has been widely performed clinically as a promising analgesic method that could avoid the side effects of analgesics but only has a short pain-free duration; researchers have clarified that the addition of dexamethasone to LIA could provide significant analgesic effects and significantly prolong the duration of analgesic effects without obvious complications for various types of surgeries. To date, no studies have evaluated the addition of dexamethasone to LIA for patients receiving craniotomy. The aim of the study was to test the hypothesis that pre-emptive scalp infiltration with a steroid (dexamethasone) plus a local anesthetic (ropivacaine) could achieve superior postoperative analgesic effects to a local anesthetic (ropivacaine) alone in adult patients undergoing a craniotomy. Study design and methods: This study is a randomized controlled trial that will include one intervention and one control group involving a total of 140 adults scheduled for elective craniotomy for resection of supratentorial tumors under general anesthesia and with an anticipated full recovery within 2 hrs postoperatively. The intervention will involve pre-emptive scalp infiltration with ropivacaine plus dexamethasone (the dexamethasone group) or ropivacaine alone (the control group), and the participants in both groups will complete a 6-month follow-up. The primary outcome will be the cumulative sufentanil consumption within 48 hrs postoperatively. Discussion: The intervention, if effective, this study will provide clinically important information on the role of dexamethasone in scalp infiltration for post-craniotomy pain management.

Pre-emptive scalp infiltration with ropivacaine plus methylprednisolone versus ropivacaine alone for relief of postoperative pain after craniotomy in children (RP/MP vs RP): a study protocol for a randomised controlled trial.

INTRODUCTION: Pre-emptive scalp infiltration with local anaesthetics is the simplest and most effective method to prevent postoperative incisional pain. However, local infiltration of an anaesthetic only provides relatively short-term pain relief. Methylprednisolone (MP) treatment, administered as an adjuvant at the wound site, has been shown to provide satisfactory pain management after lumbar laminectomy. However, there is no evidence regarding the efficacy of MP infiltration for the relief of postoperative pain after craniotomy. Currently, postoperative pain after craniotomy in children is undertreated. Therefore, we aim to investigate whether pre-emptive scalp infiltration with ropivacaine (RP) plus MP is superior to RP alone to improve postoperative pain after craniotomy in children. METHODS AND ANALYSIS: The RP/MP versus RP trial is a prospective, single-centre, randomised, parallel-group study of 100 children aged 8-18 years undergoing intracranial surgery. Participants will be randomly allocated to receive pre-emptive scalp infiltration with either RP plus MP or RP alone. The primary outcome will be the cumulative fentanyl dose administered by patient-controlled intravenous analgesia within 24 hours postoperatively. The secondary outcomes will include postoperative Numerical Rating Scale scores, pain control satisfaction scores, length of stay and adverse events. Data will be analysed by the intention-to-treat principle. ETHICAL APPROVAL AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital Affiliated to Capital Medical University (Approval Number: KY 2018-066-02). The results will be disseminated in international academic meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03636165; Pre-results.

High Expression of LTBP2 Contributes to Poor Prognosis in Colorectal Cancer Patients and Correlates with the Mesenchymal Colorectal Cancer Subtype.

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-ß in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients' clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P = 0.0071 and P < 0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and M stage (P < 0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P < 0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.