CCL2 regulated by the CTBP1-AS2/miR-335-5p axis promotes hemangioma progression and angiogenesis.

CONTEXT: Hemangioma (HA) is a benign vascular neoplasm that can lead to permanent scarring. C-C motif chemokine ligand 2 (CCL2) plays a crucial role in facilitating growth and angiogenesis during HA progression. However, the mechanism regulating CCL2 in HA remains poorly elucidated. OBJECTIVE: To elucidate the mechanism regulating CCL2 in HA. METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was employed to determine the expression levels of CCL2, long noncoding RNA (lncRNA) CTBP1 divergent transcript (CTBP1-AS2), and microRNAs (miRNAs). Proliferation, migration, invasion, and angiogenic abilities of human HA endothelial cells (HemECs) were assessed using cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell, and tube formation assays. Bioinformatics analysis, RNA pull-down, and luciferase reporter assays were conducted to investigate whether CCL2 targets miR-335-5p. Additionally, rescue experiments were performed in this study. RESULTS: CCL2 expression was markedly upregulated in HemECs. CCL2 promoted HA cell proliferation, migration, invasion, and angiogenesis while inhibiting apoptosis. CCL2 was directly targeted by miR-335-5p. Additionally, we found that CTBP1-AS2 could function as a competing endogenous RNA (ceRNA) to sponge miR-335-5p, thereby upregulating CCL2. CONCLUSION: Our findings suggest that targeting the CTBP1-AS2/miR-335-5p/CCL2 axis may hold promise as a therapeutic strategy for HA.

Effects of an intraoperative intravenous Bolus Dose of Dexmedetomidine on postoperative catheter-related bladder discomfort in male patients undergoing transurethral resection of bladder tumors: a randomized, double-blind, controlled trial.

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.

Antitumor Effects of ß-Elemene Through Inducing Autophagy-Mediated Apoptosis in Ewing Sarcoma Family Tumor Cells.

Ewing sarcoma family tumors (ESFTs) are a group of aggressive tumors mainly affecting children and young people. A compound derived from Curcuma wenyujin plant or lemon grass, ß-elemene, has exhibited antitumor effects to ESFT cells, the mechanism of which remains to be clarified further. Autophagy is involved in the antitumor effects of various drugs, whereas the role of autophagy in the antitumor effects of ß-elemene persists controversial. Herein we found that ß-elemene treatment inhibited the viability of ESFT cells in a dose-dependent manner. The increase of LC3-II level and the decrease of p62 level were observed in ß-elemene-treated cells, as well as the increase of autolysosomes, which indicated the promotion of autophagic flux. Sequentially the autophagy inhibition using 3-MA treatment or ATG5 depletion significantly reversed the viability repression and apoptosis induction by ß-elemene treatment. In addition, autophagy was found to be important in the toxic effects induced by the combination treatment of ß-elemene and IGF1R inhibition in ESFT cells. Our data suggested an essential role of autophagy in ß-elemene-induced apoptosis in ESFT cells, which is anticipated to provide novel insights to the development of ESFT treatments.

Effects of S-ketamine on Postoperative Recovery Quality and Inflammatory Response in Patients Undergoing Modified Radical Mastectomy.

INTRODUCTION: S-ketamine plays an important role in reducing postoperative pain, but its impact on the quality of recovery in breast cancer has not been clarified. We designed this trial to explore the effects of s-ketamine on the quality of postoperative recovery and inflammatory response in modified radical mastectomy. METHODS: A total of 138 patients were randomly assigned to group C (group control), group K1 (group of s-ketamine dose 1) and group K2 (group of s-ketamine dose 2). Groups K1 and K2 were given 0.1 mg/kg, 0.2 mg/kg s-ketamine intravenous (IV) after induction, followed by 0.1 mg/kg/h or 0.2 mg/kg/h continuous intravenous infusion, respectively. Group C received the same volume of saline. A 40-item Quality of Recovery Questionnaire (QoR-40) was used to assess the quality of recovery at 24 h postoperatively. Changes in inflammatory markers, nociceptive thresholds, and the occurrence of adverse events were recorded at 24 h postoperatively. RESULTS: The QoR-40 scores at 24 h postoperatively were higher in group K2 [182.00 (179.00-185.00)] compared to group K1 [174.00 (169.50-180.50)] and group C [169.00 (163.75-174.25)] (group K2 vs. group K1, P < 0.001; group K2 vs. group C, P < 0.001). At 24 h postoperatively, the neutrophil count, NLR (neutrophil-lymphocyte ratio), and CRP (C-creative protein) were all significantly lower in group K2 than group C(P < 0.05), no differences were observed between group K1 and C(P > 0.05), group K1 and K2(P > 0.05), respectively. There was no significant difference in the incidence of adverse effects among the three groups (P > 0.05). CONCLUSIONS: A high dose of s-ketamine improved the quality of recovery at 24 h after surgery, as well as alleviated the inflammatory response without increasing the incidence of adverse effects.

Association between driving pressure and postoperative pulmonary complications in patients undergoing lung resection surgery: A randomised clinical trial.

BACKGROUND: It is uncertain whether an association exists for decreases in driving pressure and the occurrence of postoperative pulmonary complications (PPCs) in patients undergoing selective lung resection surgery. Thus, we designed this study to determine whether the positive end-expiratory pressure (PEEP) titration to the lowest driving pressure compared with conventional low PEEP level during one-lung ventilation (OLV) in patients undergoing selective lung resection surgery decreases PPCs. METHODS: This single-centre, randomised trial approved by the Ethical Committee of the Sun Yat-Sen University Cancer Center involved patients who signed written consent. Patients were randomised to the PEEP titration to the lowest driving pressure group (n = 104), or to the conventional low level of PEEP group (n = 103), consisting a PEEP level of 4 cm H2O during OLV. All patients received volume-controlled ventilation with a tidal volume of 6 mL/kg of predicted body weight. The primary outcome was defined as positive if 4 or more of eight Melbourne Group Scale (MGS) variables developed within the first 3 days after surgery. The incidence of major PPCs occurring during postoperative 7 days was also recorded. RESULTS: Among 222 patients who were randomised, 207 (93%) completed the trial (109 men [53%]; mean age, 56.9 years). The primary outcome occurred in 4 of 104 patients (4%) in the PEEP titration to the lowest driving pressure group compared with 13 of 103 patients (13%) in the conventional low level of PEEP group (risk ratio, 0.32 [95% CI, 0.10-0.90]; P = 0.021). CONCLUSIONS: Among patients undergoing selective lung surgery, intraoperative OLV with PEEP titration to the lowest driving pressure compared with conventional low PEEP level (4 cm H2O) significantly reduced PPCs within the first 3 postoperative days, however, did not significantly reduce PPCs within the first 7 postoperative days.

[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

ß-elemene Isopropanolamine Derivative LXX-8250 Induces Apoptosis Through Impairing Autophagic Flux via PFKFB4 Repression in Melanoma Cells.

Melanoma is a highly aggressive skin cancer and accounts for most of the skin cancer-related deaths. The efficacy of current therapies for melanoma remains to be improved. The isopropanolamine derivative of ß-elemene LXX-8250 was reported to present better water solubility and stronger toxicity to tumor cells than ß-elemene. Herein, LXX-8250 treatment showed 4-5-fold more toxicity to melanoma cells than the well-known anti-melanoma drug, Dacarbazine. LXX-8250 treatment induced apoptosis remarkably, which was caused by the impairment of autophagic flux. To clarify the molecular mechanism, microarray analyses were conducted, and PFKFB4 expression was found to be suppressed by LXX-8250 treatment. The cells overexpressed with PFKFB4 exhibited resistance to apoptosis induction and autophagic flux inhibition by LXX-8250 treatment. Moreover, LXX-8250 treatment suppressed glycolysis, to which the cells overexpressed with PFKFB4 were tolerant. LXX-8250 treatment inhibited the growth of melanoma xenografts and suppressed PFKFB4 expression and glycolysis in vivo. Taken together, LXX-8250 treatment induced apoptosis through inhibiting autophagic flux and glycolysis in melanoma cells, which was mediated by suppression of PFKFB4 expression. The study provides a novel strategy to melanoma treatment.

Evaluation of digestibility differences for apple polyphenolics using in vitro elderly and adult digestion models.

We evaluated the in vitro digestibility of apple polyphenols mimicking elderly and adult digestion models (dynamic and static systems). The digestibility of total apple polyphenols in small intestine was much higher in the adult dynamic system (62 µg/100 g fresh apple) compared to the static system (20 µg/100 g fresh apple) and elderly dynamic digestion conditions (33 µg/100 g fresh apple). Elderly in vitro static digestion showed better antioxidant activity than the adult system (OH and ABTS+ methods). Thus, the in vitro dynamic digestion system can more truly reflect the digestion of apple polyphenols than static digestion system. Moreover, elderly digestion conditions negatively influenced the digestibility of apple polyphenols including chlorogenic acid, epicatechin, phlorizin, rutin, phloretin, hyperoside, proanthocyanidin B2, and quercetin. Hence, appropriate selection of in vitro digestion models for elderly is a prerequisite to exploring the digestibility of phytochemicals for the development of functional food products for elderly.

[Application of thin free lateral femoral circumflex artery perforator flap in repair of scar contracture deformity in hand and foot].

OBJECTIVE: To explore the effectiveness of thin free lateral femoral circumflex artery perforator flaps that dissected under the superficial fascia in repair of scar contracture deformity in hand and foot. METHODS: Between January 2017 and October 2020, 15 patients with scar contracture deformity in hand or foot were admitted. There were 9 males and 6 females; aged 6-42 years, with a median age of 23 years. Scar contracture lasted from 1 to 21 years, with a median of 13 years. There were 11 cases of scar contracture deformities in the hands and 4 cases in the feet, all of which showed different degrees of hand and foot joint dysfunction. After the scar contracture was released, the size of wounds ranged from 6 cm×4 cm to 9 cm×8 cm, including 12 cases with exposure of blood vessels, nerves, or tendons, and 4 cases with tendon defects. A thin free lateral circumflex femoral artery perforator flap that dissected under the superficial fascia was used to repair the wound. The size of flap ranged from 6.0 cm×5.0 cm to 10.0 cm×8.5 cm. Fascia strips were used to reconstruct tendons and the donor sites were sutured directly. RESULTS: The venous vascular crisis occurred in 1 flap, and the flap survived successfully after treatment. The rest flaps survived well, and the wounds healed by first intention. All incisions at donor sites healed by first intention. All patients were followed up 6-12 months after operation, with an average of 9 months. The flaps were in good shape and texture. The functions of the affected hand had been restored to a large extent. According to the upper limb function evaluation standard of the Society of Hand Surgery of the Chinese Medical Association, 7 cases were excellent and 4 cases were good. The deformity of the toe joint of the affected foot significantly improved. No muscular hernia, sensory numbness, or other complications occurred at the donor sites. CONCLUSION: The thin free lateral femoral circumflex artery perforator flap that dissected under the superficial fascia is an effective method to repair scar contracture deformity of hand and foot with well appearance, good function recovery, and less complication of the donor sites.

[Repair of complex wounds of limbs with free lobed perforator flaps].

OBJECTIVE: To explore the effectiveness of free lobed perforator flaps in repairing of complex wounds of limbs. METHODS: Between January 2018 and January 2021, 10 patients with complex wounds of limbs were admitted. There were 7 males and 3 females, aged from 32 to 64 years, with an average age of 45 years. There were 4 cases of traffic accident injuries, 3 cases of machine strangulation injuries, 1 case of machine crush injury, and 2 cases of heavy object crush injuries. There were 5 cases of upper limb wounds and 5 cases of lower limb wounds. The size of wounds ranged from 11 cm×10 cm to 25 cm×18 cm. The wounds were repaired with tri-lobed flaps of the descending branch of the lateral femoral circumflex artery in 7 cases, four-lobed flaps in 2 cases, and with tri-lobed flaps of the descending branch of the lateral femoral circumflex artery combined with oblique branch in 1 case. The size of flaps ranged from 12.0 cm×10.5 cm to 28.0 cm×12.0 cm. The donor sites were sutured directly in 9 cases and repaired with superficial iliac circumflex artery perforator flap in 1 case. RESULTS: Sinus formed at the edge of the flap in 1 patient, which healed after dressing change and drainage; other flaps survived well, and the wounds healed by first intention. The skin flap at donor site survived, and the incisions healed by first intention. All patients were followed up 6-24 months (mean, 11 months). All flaps had good appearance and function, and linear scars were left at the donor site without obvious complications. CONCLUSION: Free lobed perforator flap is an alternative method to repair complex wounds of limbs with high safety, good effectiveness, and less complications.

PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40.

Autophagy predominantly promotes cell survival by recycling cell components, while it kills cells in specific contexts. Cell death related to autophagy plays important roles in multiple physiological and pathological situations including tumorigenesis, and the mechanism needs to be defined further. PRAS40 was found to be crucial in various cancers, and phosphorylation was reported to be involved in autophagy inhibition in monocytes. However, the detailed role of PRAS40 in autophagy and the relationship to tumorigenesis remain largely unknown. Herein we screened the binding partners of PRAS40, and found that PRAS40 interacted with Phosphoglycerate kinase 1 (PGK1). PGK1 phosphorylated PRAS40 at Threonine 246, which could be inhibited by blocking the interaction. Both in vitro and in vivo results revealed that PRAS40 mediated PGK1-induced cell growth. By tracing the mechanism, we found that PGK1 suppressed autophagy-mediated cell death, in which PRAS40 was crucial. Thus PGK1 phosphorylates PRAS40 to repress autophagy-mediated cell death under normoxia, promoting cellular proliferation. The binding of PGK1 to PRAS40 was transferred to Beclin1 under hypoxia, resulting in the increase of Beclin1 phosphorylation. These results suggest a novel model of tumorigenesis, in which PGK1 switches between repressing autophagy-mediated cell death via PRAS40 and inducing autophagy through Beclin1 according to the environmental oxygen level. Our study is anticipated to be able to offer novel insights in understanding PGK1/PRAS40 signaling hyperactivated cancers.

Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial.

BACKGROUND: CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. METHODS: Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. RESULTS: To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). CONCLUSIONS: Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

Diagnostic value of microRNA­125b in peripheral blood mononuclear cells for pulmonary tuberculosis.

Pulmonary tuberculosis (TB) is a chronic respiratory infectious disease. Certain microRNAs (miRNAs or miRs) are reported to be involved in regulating TB progression. The present study aimed to evaluate the diagnostic potential of miR­125b in pulmonary TB. The expression levels of miR­125b and Raf1 proto­oncogene serine/threonine protein kinase (RAF1) were analyzed via reverse transcription­quantitative (RT­q)PCR in patients with TB. The correlation between miR­125b and the clinical indicators was investigated, and a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR­125b. The relationship between miR­125b and RAF1 was examined using the dual luciferase reporter gene assay. IL­6, TNF­α, NF­κB and IFN­Î³ levels were detected using ELISA kits, and then the correlation between miR­125b expression and the levels of IL­6, TNF­α, NF­κB, IFN­Î³ and RAF1 in peripheral blood mononuclear cells (PBMCs) was analyzed. Moreover, RAF1 mRNA and protein expression levels were detected via RT­qPCR and western blotting. The results demonstrated that miR­125b expression was decreased in patients with TB, while RAF1 expression was increased. Furthermore, miR­125b expression was associated with sputum acid­fast bacillus smear. The area under the ROC curve of miR­125b was 0.9413, and the sensitivity and specificity of miR­125b expression for TB were 90 and 92.5%, respectively. IL­6, TNF­α, NF­κB and IFN­Î³ levels were negatively correlated with miR­125b expression, and were inhibited by miR­125b in PBMCs. Moreover, miR­125b targeted RAF1 to negatively regulate its expression levels. RAF1 reversed the role of miR­125b in attenuating IL­6, TNF­α, NF­κB and IFN­Î³ levels in PBMCs. The present study demonstrated that the levels of IL­6, TNF­α, NF­κB and IFN­Î³ were negatively correlated with miR­125b expression in PBMCs. Thus, it was suggested that miR­125b served important roles in the occurrence and development of TB by decreasing the levels of IL­6, TNF­α, NF­κB and IFN­Î³ by inhibiting RAF1.

Case Report: A Preferred Reconstructing Modality to Restore Neoplastic Nasal Alar Subunit Defects: Sequential Facial Artery Perforator Flaps.

BACKGROUND: Achieving perfect repair of a nasal defect with the recovery of cosmetic subunits has become a challenge to plastic, dermatologic, and head and neck surgeons. The study aimed to evaluate the effect of reconstructing neoplastic nasal alar subunit defects with sequential facial artery perforator flaps produced from nasolabial groove tissue. METHODS: A retrospective analysis of 20 patients who had undergone reconstruction for neoplastic nasal alar defects with this technique from January 2017 to October 2019 was performed. The reconstruction procedure used sequential facial artery perforator flaps. The surgical procedure used and follow-up results achieved have been documented photographically for all patients. RESULTS: The aesthetic and functional results of surgery were satisfactory in all the 20 patients. After all surgeries, the reconstructed alar tissues were compliant, bilateral symmetries of the alae and nasolabial grooves were satisfactory, and no patients exhibited color mismatches between the flaps and surrounding tissues. During a mean follow-up period of 22 months, none of the patients exhibited alar retraction, inferior displacement, deformation, or hypertrophic scarring. CONCLUSIONS: The sequential facial artery perforator flap technique created with nasolabial groove tissue to reconstruct neoplastic nasal alar defects is a simple single-stage procedure that provides excellent surgical outcomes.

Effects of an Intraoperative Intravenous Bolus Dose of Dexmedetomidine on Remifentanil-Induced Postinfusion Hyperalgesia in Patients Undergoing Thyroidectomy: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Consecutive exposure to high-dose remifentanil during anesthesia may induce remifentanil-induced postinfusion hyperalgesia (RPH). Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, may have synergistic effects with opioids and aid in perioperative pain management. In this study, we hypothesized that an intraoperative bolus dose of intravenous dexmedetomidine could alleviate RPH in patients undergoing thyroidectomy under general anesthesia. METHODS: Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups: placebo, normal saline (group P); low-dose dexmedetomidine 0.2 µg·kg-1 (group LD); or high-dose dexmedetomidine 0.5 µg·kg-1 (group HD). Remifentanil was infused at a rate of 0.30 µg·kg-1·minute-1. Mechanical pain thresholds were measured using an Electronic von Frey device preoperatively and at 30 minutes, 6 hours, 24 hours, and 48 hours after surgery and were analyzed with 2-way repeated-measures analysis of variance (ANOVA) followed by Bonferroni post hoc comparison. We also recorded postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 48 hours after surgery. RESULTS: The mechanical pain thresholds around the skin incision were significantly higher in group LD compared to group P 30 minutes and 6 hours after surgery (mean ± standard deviation: [65.0 ± 25.2] vs [49.6 ± 24.4] g, mean difference [95% confidence interval]: 15.4 [0.3-30.5] g, P = .045 at 30 minutes; [65.9 ± 24.5] vs [49.3 ± 26.1] g, 16.6 [1.1-32.1] g, P = .032 at 6 hours). The pain thresholds around the skin incision were significantly higher in group HD compared to group P 30 minutes and 6 hours after surgery ([67.8 ± 21.7] vs [49.6 ± 24.4] g, 18.2 [3.1-33.3] g, P = .013 at 30 minutes; [68.3 ± 22.5] vs [49.3 ± 26.1] g, 19.0 [3.5-34.5] g, P = .011 at 6 hours). The incidence of hyperalgesia around the skin incision was lower in group HD than in group P 30 minutes and 6 hours after surgery (4 [13%] vs 14 [48%], P = .012 at 30 minutes, 4 [13%] vs 12 [41%], P = .045 at 6 hours), although no significant difference was observed between group LD and group P. Postoperative pain scores, the incidence of rescue analgesic demand, and postoperative side effects were not significantly different between the groups. CONCLUSIONS: An intraoperative intravenous bolus dose of dexmedetomidine 0.5 µg·kg-1 alleviates remifentanil-induced hyperalgesia in patients undergoing thyroidectomy without a significant difference in side effects.

PD-L1 expression in colorectal cancer and its relationship with TLR-4 expression.

PURPOSE: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid tumors, but the prognostic value of PD-L1 expression in colorectal cancer (CRC) remains unclear. The aim of this study was to clarify the role of PD-L1 expression in predicting prognosis, and then provide further insight into the relation between PD-L1 and toll like receptor-4 (TLR-4) in CRC progression. METHODS: The expression of PD-L1 and TLR-4 in patients with resected CRC was analyzed using immunohistochemistry (IHC). The biological relation of PD-L1 and TLR-4 in CRC was explored using gene set enrichment analysis (GSEA). RESULTS: Positive PD-L1 and TLR-4 expression in tumor cells were observed in 12.7% and 41.2% respectively. High PD-L1 and TLR-4 expression levels were significantly correlated with poor disease-free survival. PD-L1 expression was closely associated with TLR-4 expression. Multivariate analyses further confirmed that increased expression levels of PD-L1 are unfavorable prognostic factors for operable CRC. CONCLUSION: High PD-L1 expression can be used as a prognostic indicator for patients with operable CRC. PD-L1 expression is associated with TLR-4 expression, thereby providing a theoretical basis for the combined use of PD-1/PD-L1 inhibitors and TLR agonists.

Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota.

We investigated the neuroprotective effects of baicalin and the role of gut microbiota in a mouse model of cerebral ischemia-reperfusion injury. Repeated cerebral ischemia-reperfusion significantly increased plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and clusterin (a neuroinflammation biomarker). These changes correlated with cognitive decline; short-term memory deficits; abnormal long term potentiation (LTP); decreased functional connectivity (FC) between various brain regions; reduced plasticity and dendritic spine density in the hippocampus; increased levels of the pro-inflammatory cytokines IL-1ß, IL-6, and TNFα; and altered the gut microbial composition. Treatment with 50-100 mg/Kg baicalin for 7 days after cerebral ischemia-reperfusion significantly restored normal plasma levels of TMA, TMAO, and clusterin. Baicalin treatment also suppressed neuroinflammation, remodeled the gut microbial composition back to normal, and improved cognition, memory, LTP, cerebral FC, and hippocampal neuronal plasticity. The neuroprotective effects of baicalin were diminished when mice undergoing repeated cerebral ischemia-reperfusion were pretreated with broad-spectrum antibiotics to deplete gut microbial populations. This suggests the neuroprotective effects of baicalin in cerebral ischemia-reperfusion injury are mediated by the gut microbiota. It thus appears that baicalin ameliorates neuropathology in a repeated cerebral ischemia-reperfusion model mice by remodeling the gut microbiota.

PRAS40 hyperexpression promotes hepatocarcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers, whereas the molecular mechanism remains largely unknown. PRAS40 (encoded by AKT1S1) phosphorylation was increased in human melanoma, prostate cancer and lung cancer specimens, which was considered as the results of Akt activation. However the mechanism in detail and its role in HCC stay elusive. METHODS: PRAS40 expression and phosphorylation were analyzed in HCC specimens, and the survival rates of patients were investigated. Functional analyses of PRAS40 in HCC were performed in vivo and in vitro. The miR-124-3p binding sites in PRAS40 were investigated using luciferase assay. MiR-124-3p expression in HCC specimens was examined by In Situ hybridization, and the correlation to PRAS40 level was evaluated. FINDINGS: The phosphorylation, protein and mRNA levels of PRAS40 were increased significantly in HCC specimens from our cohorts and TCGA database, which was positively correlated to the poor prognosis of HCC patients. Compared to Akt1s1+/+ mice, hepatocarcinogenesis was suppressed in Akt1s1-/- mice, and the activation of Akt was impaired. PRAS40 depletion resulted in the inhibition of HCC cellular proliferation. Tumor suppressor miR-124-3p was found to downregulate PRAS40 expression by targeting its 3'UTR. MiR-124-3p levels were inversely correlated to PRAS40 protein and phosphorylation levels in HCC specimens. The proliferation inhibition by miR-124-3p mimics was partially reversed by exogenous PRAS40 introduction in HCC cells. INTERPRETATION: PRAS40 hyperexpression induced by loss of miR-124-3p contributes to PRAS40 hyperphosphorylation and hepatocarcinogenesis. These results could be expected to offer novel clues for understanding hepatocarcinogenesis and developing approaches.

A randomised comparison of the efficacy of a Coopdech bronchial blocker and a double-lumen endotracheal tube for minimally invasive esophagectomy.

BACKGROUND: Both a bronchial blocker (BB) and a double-lumen endotracheal tube (DLT) can achieve lung collapse and one-lung ventilation (OLV) during thoracic surgery. The purpose of this study was to compare these two airway devices in terms of efficacy in video-assisted thoraco-laparoscopic esophagectomy for cancer. METHODS: A total of 55 patients underwent combined thoracoscopic and laparoscopic esophagectomy for cancer were enrolled and divided into a Coopdech bronchial blocker group (CBB group, n=27) or a DLT group (DLT group, n=28). The primary outcome was the lung collapse scores at 1, 5, 10 minutes after the opening of the pleural and assessed using a verbal analogue scale via a real-time video view. Secondary outcomes including time for tube localization, incidence of tube displacement, postoperative sore throats, and surgeons' satisfaction with surgical manipulations were collected. RESULTS: The patients in the CBB group achieved better lung collapse scores at 5 minutes (7.4±1.3 vs. 6.4±0.9 minutes, P<0.01) and 10 minutes (8.9±0.8 vs. 7.1±0.9 minutes, P<0.01) after opening the pleura, and they had lower incidence of postoperative sore throats [5 (18%) vs. 16 (57%), P<0.01] when compared with patients in DLT group. However, the time for tube localization were significantly longer in CBB group than in DLT group (210±120 vs. 125±60 s, P<0.05). There were no significant difference in tube displacement, hypoxemia (SpO2 <90%) during OLV, and in surgeons' satisfaction with surgical manipulations. CONCLUSIONS: CBB technique can be a potential alternative to the conventional DLT strategy for lung collapse and OLV during esophagectomy.

Effect of Remote Ischemic Preconditioning in Patients Undergoing Hepatectomy With Portal Triad Clamping: A Randomized Controlled Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce liver injury in patients undergoing hepatectomy for colorectal liver metastasis, but its role is unclear in hepatocellular carcinoma patients with portal triad clamping during hepatectomy. METHODS: In this prospective, randomized trial, 140 patients with hepatocellular carcinoma undergoing liver resection requiring portal triad clamping were randomized to a RIPC group or a control group. Patients in the RIPC group received RIPC (3 cycles of 5-minute ischemia and 5-minute reperfusion in right upper limb with cuff pressure at 30 kPa [225 mm Hg]) approximately 10 minutes after induction of anesthesia. In the control group, patients received sham RIPC (the cuff was not inflated). The primary outcome was the postoperative peak level of total bilirubin (TBIL) and was analyzed with the independent t test. Secondary outcomes were liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. RESULTS: Data from 136 patients (69 in the RIPC group and 67 in the control group) were analyzed. The RIPC group had on average a 5.9 µmol lower peak level of TBIL than the control group; the mean difference is -5.9, and the 95% confidence interval (CI) reverses to -17.9 to 6.1. There were no significant differences between the 2 groups in liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. CONCLUSIONS: We found no evidence that RIPC can reduce postoperative liver injury after hepatectomy.