Effect of S-Ketamine on Postoperative Nausea and Vomiting in Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial.

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.

The tRF-3024b hijacks miR-192-5p to increase BCL-2-mediated resistance to cytotoxic T lymphocytes in Esophageal Squamous Cell Carcinoma.

The limited efficacy of immune checkpoint inhibitors (ICIs) in the treatment of advanced Esophageal Squamous Cell Carcinoma (ESCC) poses a challenge. Recent evidence suggests that tumor cells' insensitivity to cytotoxic T lymphocytes (CTLs) contributes to drug resistance against ICIs. Here, a particular tRNA-derived fragment called tRF-3024b has been identified as playing a significant role in tumor cell resistance to CTLs. Through tRF sequencing (tRF-seq), we observed a high expression of tRF-3024b in ESCC cells that survived co-culture with CTLs. Further in vitro studies demonstrated that tRF-3024b reduced the apoptosis of tumor cells when co-cultured with CTLs. The mechanism behind this resistance involves tRF-3024b promoting the expression of B-cell lymphoma-2 (BCL-2) by sequestering miR-192-5p, a microRNA that would normally inhibit BCL-2 expression. This means that tRF-3024b indirectly enhances the protective effects of BCL-2, reducing apoptosis in tumor cells. Rescue assays confirmed that the suppressive function of tRF-3024b relies on BCL-2. In summary, the tRF-3024b/miR-192-5p/BCL-2 axis sheds light on the crucial role of tRF-3024b in regulating BCL-2 expression. These findings offer valuable insights into strategies to enhance the response of ESCC to CTLs and improve the effectiveness of immunotherapy approaches in treating ESCC.

Prophylactic fat-free diet in patients undergoing lobectomy for lung cancer does not decrease postoperative chylothorax: Results from a single-center retrospective study.

PURPOSE: Reliable measures to prevent chylothorax following lobectomy are lacking. Herein a case-control study was conducted to investigate the effect of prophylactic fat-free diet on the incidence of chylothorax after thoracoscopic lobectomy and systemic lymph node dissection (SLND) for lung cancer. METHODS: Between January 2015 and December 2017, the patients with primary non-small cell lung cancer who underwent lobectomy and SLND were retrospectively reviewed. Patients in the prophylactic group started fat-free diet one week before the surgery until removal of the chest tubes after the operation; while those in the control group took normal diet unless the onset of chylothorax. Logistic regression analysis was utilized to identify the predictive factors of chylothorax following lobectomy. RESULTS: The data of 110 patients in the control group and 115 cases in the prophylactic group were collected. The patients in prophylactic group showed less intraoperative blood loss [(79.9±48.7) mL vs. (100.9±55.6) mL, p=0.003], reduced postoperative drainage volume [(504.3±268.0) mL vs. (714.1±618.5) mL, p=0.001], and shorter chest tube duration [(3.6±1.7) days vs. (4.2±2.6) days, p=0.014]; however, a similar incidence of chylothorax [3 (2.6%) vs. 7 (6.4%), p=0.207] was recorded. Multivariate logistic regression analysis indicated that neoadjuvant therapy was an independent positive factor of chylothorax (odd ratio [OR] = 9.257; 95% confidence interval [CI] 1.434-59.773, p=0.019); whereas high-volume experience of the surgeon was an independent negative factor of this complication (OR = 0.129; 95% CI 0.017-0.982, p=0.048). CONCLUSION: Prophylactic fat-free diet does not decrease the incidence of chylothorax after lobectomy. Further well-designed trials are warranted to verify this occasional finding.

Neoadjuvant apatinib plus S-1 in locally advanced pulmonary adenocarcinoma: A case report and review of the literature.

RATIONALE: About one-third of the lung tumors are staged as locally advanced at the time of initial diagnosis; however, the optimal induction treatment before curative resection has not been elucidated. To date, the evidence regarding the preoperative apatinib plus S-1 for locally advanced pulmonary adenocarcinoma is scarce. PATIENT CONCERNS: A 29-year-old female was admitted because of persistent cough, sputum, and chest distress for 2 months. DIAGNOSES: Primary pulmonary adenocarcinoma (cT3N2M0, IIIB) with unknown driver gene mutation status. INTERVENTIONS: The patient had received 4 months of neoadjuvant therapy using oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval), followed by anatomical lobectomy with curative intent. Adjuvant apatinib (425 mg daily for a month, and 250 mg daily for another month) plus S-1 at the same dosage were administered for 2 months. Thereafter, maintenance of low-dose S-1 monotherapy (40 mg, twice daily for 4 weeks with a 2-week drug-free interval) was continued for 6 months. OUTCOMES: The adverse events were tolerable and well-controlled. A postoperative recurrence-free survival for 2 years and a half up to now was indicated. LESSONS: Preoperative apatinib plus S-1 showed efficacy in locally advanced pulmonary adenocarcinoma. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Prophylactic octreotide does not reduce the incidence of postoperative chylothorax following lobectomy: Results from a retrospective study.

Chylothorax after lobectomy is common, lacking reliable preventive measures. Octreotide is widely used for treatment of chyle leakage, but its role in preventing chylothorax has not been estimated. The aim of this study was to evaluate whether prophylactic octreotide could reduce the incidence of postoperative chylothorax.Patients who underwent lobectomy for lung cancer from January 2016 to September 2018 were retrospectively reviewed. The cases in prophylactic group received octreotide 1 day before the surgery until removal of chest tubes, while those in the control group did not use it unless the diagnosis of chylothorax.A total of 379 patients were enrolled, with 190 patients in control and 189 cases in prophylactic group. Octreotide was well tolerated in patients who received this agent. No 30-day mortality was indicated. Seven cases in control (3.7%, 7/190) and 3 cases in prophylactic group (1.6%, 3/189) with chylothorax were observed (P = .337). The patients in prophylactic group showed shorter duration of chest drainage ([3.6 ±â€Š1.6] days vs [4.1 ±â€Š2.0] days, P = .006) and reduced drainage volume ([441.8 ±â€Š271.1] mL vs [638.7 ±â€Š463.3] mL, P < .001). In addition, they showed similar stations and numbers of dissected lymph nodes, surgery-related complications, and postoperative hospital stay. Besides, 11 (5.8%, 11/190) patients in control and 6 (3.2%, 6/189) cases in the prophylactic group were readmitted for pleural effusion needing reinsertion of chest tubes (P = .321). Moreover, multivariable logistic analysis showed that induction therapy (odds ratio [OR] =12.03; 95% confidence interval [CI] 3.15-46.03, P < .001) was a risk factor, while high-volume experience of the surgeon (OR = 0.23; 95% CI 0.06-0.97, P = .045) was a preventive factor of surgery-related chylothorax. Additionally, prophylactic octreotide (OR = 0.18; 95% CI 0.11-0.28, P < .001) and perioperative low-fat diet (OR = 0.46; 95% CI 0.29-0.73, P = .001) were negatively associated with the drainage volume of pleural effusion. Furthermore, high-volume experience of the surgeon (OR = 6.03; 95% CI 1.30-27.85, P = .021) and induction therapy (OR = 8.87; 95% CI 2.97-26.48, P < .001) were risk factors of unplanned readmission.Prophylactic octreotide does not reduce the incidence of postoperative chylothorax or unplanned readmission following anatomic lobectomy. The routine application of octreotide should not be recommended. High-quality trials are required to validate these findings.

Solitary thin-walled cystic lung cancer with extensive extrapulmonary metastasis: A case report and review of the literature.

RATIONALE: Asymptomatic, isolated, and thin-walled cystic lung cancer with extensive extrapulmonary metastasis is rare, and the risk of pulmonary cyst developing into lung cancer is poorly understood. The efficacy of apatinib for end-stage pulmonary adenosquamous carcinoma has not been clarified yet. PATIENT CONCERNS: We herein report a rare case of primary lung cancer that appeared as an isolated thin-walled cystic lesion on computed tomography (CT) image, who was initially misdiagnosed as having pulmonary cyst empirically. DIAGNOSES: Fluorine-18-fluorodeoxyglucose-positron emission tomography and CT-guided liver biopsy of the patient revealed extra-pulmonary metastasis of lung cancer. INTERVENTIONS: Eight cycles of cisplatin-based chemotherapy were administered, followed by oral apatinib for 6 months. Thereafter, best supportive care was given for this patient. OUTCOMES: The pulmonary cystic lesion indicated stable disease through the therapy, but the hepatic tumors were progressed gradually after anticancer treatment. The patient died 16 months after the correct diagnosis. LESSONS: Solitary thin-walled cystic lung cancer should be kept in mind during the differential diagnosis of pulmonary cavitary lesions. Chest CT alone is insufficient for surveillance of these cystic diseases. Timely biopsy and resection are essential to avoid delayed management. Besides, apatinib may play a role in the treatment of end-stage pulmonary adenosquamous carcinoma.

Expression of HSPA12B in acute cardiac allograft rejection in rats.

HSP70 may play a more important role in regulating antigen-specific immune response than other HSPs; however, HSPA12B production in transplanted heart remains obscure, which was identified as the newest member of the HSP70 family. In the current study, we performed a heart transplantation model in adult rats and investigated the dynamic changes of HSPA12B expression in the cardiac grafts. The cardiac grafts of allogeneic (Wistar-Lewis rat) and syngeneic (Lewis-Lewis rat) rat models were subjected to histopathological and immunohistochemical analyses for HSPA12B expression on days 0-7 after operation. We also examined the expression profiles of active caspase-3, whose changes were correlated with the expression profiles of HSPA12B. Our results demonstrated that HSPA12B protein exhibited biphasic patterns in transplanted heart. The first expression phase correlated with ischemical reperfusion injury over 2 days post-transplant. The second peak of HSPA12B expression was found only in allografts on day 5, concurrent with the expression of caspase-3. Immunohistochemical assay showed that compared with rare expression in isografts, there were significant protein expressions of HSPA12B and caspase-3 in heart allografts from day 5 to 7 post-transplant. Furthermore, double immunofluorescence staining for active caspase-3 and HSPA12B in isografts and allografts at day 5 post-transplant were analyzed and colocalization of HSPA12B/active caspase-3 was detected in allografts. In conclusion, this is the first description of HSPA12B expression in acute cardiac allograft rejection. Our results suggested that HSPA12B might play crucial roles in heart pathophysiology after transplantation.

Pyruvate kinase isoenzyme M2 expression correlates with survival of cardiomyocytes after allogeneic rat heterotopic heart transplantation.

The aim of our study was to assess correlations between PKM2 and the survival of cardiomyocytes after heart transplantation in rat. The PKM2, Bcl-xl, active caspase-3 proteins were detected by western blot, and PKM2 was testified by immunohistochemistry and immunofluorescence. At the same time, active caspase-3, α-actinin, VCAM-1, and CD4 were detected by immunofluorescence. Compared with rare expression in syngeneic Lewis rat hearts, the PKM2 protein level in allogeneic hearts was detected at various survival times after transplantation, which prominently expressed on day five postoperatively. In addition, we examined the expression of Bcl-xl and active caspase-3 in allogeneic hearts, which has a similar expression pattern with PKM2. Immunohistochemical and immunofluorescent methods displayed that PKM2 was widely expressed in cardiac tissue, and active caspase-3 was also expressed in cardiomyocytes. However, the PKM2 was not expressed in T cells and other immune response cells. These results suggested that PKM2 may regulate the survival of cardiomyocytes in acute rejection after heart transplantation in rat.

Correlation of serum- and glucocorticoid-regulated kinase 1 expression with ischemia-reperfusion injury after heart transplantation.

IRI of a transplanted heart may result in serious early and late disadvantageous effects such as increased allograft immunogenicity, primary graft dysfunction, and initiation of fibroproliferative cascades that compromise the survival of the recipient. Sgk-1 has recently been linked to cell growth and survival. It has been reported that through a renal transplantation model, Dexa increases Sgk-1 expression and therefore protects from renal IRI. In our current study, we aim to assess the expression of Sgk-1 and its protective effects on cardiomyocyte IRI after heart transplantation. Heart allograft model was performed from Wistar into Lewis, and isograft model was from Lewis into Lewis. Grafts were then harvested at one, six, 12, or 24 h post-transplantation for Sgk-1 expression analyses. In some groups, part donors were treated with Dexa 2 h prior at doses of 0.05, 0.5 and 2 mg/BWkg, respectively. Sgk-1 expression was markedly increased in grafted heart 6-12 h post-transplantation in both the allogenic and isogenic models. Immunostaining experiments confirmed that Sgk-1 was expressed in cardiomyocytes rather than infiltrated immune cells. Furthermore, Dexa treatment significantly increased Sgk-1 expression and the donor cardiomyocyte injury was greatly minimized by Dexa treatment. These results suggest that induction of Sgk-1 might explain some of the beneficial impact of corticosteroids in IRI and hence might have therapeutic implications.

Identification of Gem as a new candidate prognostic marker in hepatocellular carcinoma.

GTP binding protein overexpressed in skeletal muscle (Gem) is a Ras-related protein whose expression is induced in several cell types upon activation by extracellular stimuli. To investigate the potential roles of Gem in hepatocellular carcinoma (HCC), expression of Gem was examined in human HCC samples. Western blot analysis showed that compared with primary human hepatocytes and adjacent noncancerous tissue, significant down-regulation of Gem was found in HCC cells and tumor tissues. In addition, immunohistochemical analysis of Gem expression was investigated in 108 specimens of HCC tissues. Clinicopathological data were collected to analyze the association with Gem expression. Expression of Gem was significantly negatively correlated with histological grade (P=0.001), tumor size (P=0.020), and vascular invasion (P=0.005), and Gem was also negatively correlated with proliferation marker Ki-67 (P<0.01). More importantly, the Kaplan-Meier survival curves analysis revealed that low expression of Gem was associated with poor prognosis in HCC patients. Univariate analysis showed that Gem expression was associated with poor prognosis (P=0.006). Multivariate analysis indicated that Gem expression was an independent prognostic marker for HCC (P=0.007). Finally, serum starvation and release experiments showed that Gem expression was negatively related with cell proliferation. In the conclusion, our results suggested that down regulation of Gem expression was involved in the pathogenesis of hepatocellular carcinoma, and it might be a favorable independent prognostic parameter for HCC.

The expression levels and prognostic value of high temperature required A2 (HtrA2) in NSCLC.

High temperature required A2 (HtrA2) is a serine kinase that is released from mitochondria into the cytosol upon apoptotic stimuli, inducing apoptosis in various cancers. Thus, analysis of the expression of HtrA2 in non-small-cell lung cancer (NSCLC) tissues is needed for the understanding of this malignancy. In this study we firstly analyzed the apoptosis effect of HtrA2 in A549 cells by RNA interference and cisplatin with Western blot and flow cytometry. Then HtrA2 expression was evaluated by Western blot and immunohistochemistry in NSCLC tissues. Western blot and flow cytometry analyses indicated that deletion of HtrA2 was negatively correlated with apoptosis-induced protein in A549 cells. HtrA2 was lowly expressed in NSCLC and significantly associated with histological differentiation and clinical stage. Besides, low expression of HtrA2 was a prognostic factor for NSCLC patients' inferior survival. In conclusion, HtrA2 might promote the apoptosis of NSCLC cells, and serve as a target for NSCLC's treatment.

Upregulation of α-enolase in acute rejection of cardiac transplant in rat model: implications for the secretion of interleukin-17.

Acute allograft rejection remains a major problem in solid organ transplantation. The enzyme α-enolase has been shown to induce an immune response in cardiac transplantation. In this study, we investigated the role of α-enolase in acute allograft rejection in a rat model of heart transplantation. Hearts from either (WF: RT1(u) ) or (Lew: RT1(1) ) rats were transplanted into (Lew: RT1(1) ) rats. No rejection occurred in the isograft group, for which the median survival time was >168 days, whereas the median survival time of the allograft group was significantly less at 10 ± 2.1 days (n = 8 per group, p < 0.001). Increased inflammation was observed in allografts, including increased α-enolase expression and increased numbers of infiltrating CD4(+) T cells (p < 0.05). By immunohistochemical staining, we confirmed that α-enolase was expressed not only in myocardial cells but also in the infiltrating lymphocytes. However, on the fifth day after transplantation, α-enolase expression was no longer observed in the lymphocytes (n = 3, p < 0.001). In contrast, no lymphocytes were found in isografts after transplantation (n = 3, p < 0.001). α-enolase expression was increased in lymphocytes, which are implicated in the acute rejection of cardiac transplants. Intragraft α-enolase inhibition may be useful as an adjuvant therapy to systemic immunosuppression in heart transplantation.

Increased expression of glycinamide ribonucleotide transformylase is associated with a poor prognosis in hepatocellular carcinoma, and it promotes liver cancer cell proliferation.

Glycinamide ribonucleotide transformylase (GART) is a folate-dependent enzyme in the de novo purine pathway that has been the target of antineoplastic intervention for almost 2 decades. Until now, its expression and functional significance in hepatocellular carcinoma (HCC) have been unclear. We demonstrated by Western blotting that the expression of GART was markedly up-regulated in HCC patients. Immunohistochemistry staining was used to determine the expression of GART in HCC and adjacent nontumor tissues from 96 patients. Increased expression of GART correlated positively with the histologic grade (P = .001), tumor size (P = .043), number of tumorous nodes (P = .020), and intrahepatic metastases (P = .031), suggesting a role for GART in the progression of HCC. Patients with higher GART expression had a much worse overall survival rate than those with low expression (P = .002). Furthermore, multivariate analysis showed that GART expression was an independent predictor of overall survival (hazard ratio, 2.265; 95% confidence interval, 1.335-3.842; P = .002). Depletion of GART by small interfering RNA inhibited cell proliferation and blocked S-phase and mitotic entry in cultured HepG2 and BEL-7404 cells. Western blot analyses showed that GART depletion decreased the proliferating cell nuclear antigen concentration. Collectively, our clinical and in vitro data indicate that GART expression may be one of the causative factors for a poor prognosis in HCC.

Polycomb group oncogene RING1 is over-expressed in non-small cell lung cancer.

Ring finger protein 1 (RING1) have recently been reported to be related to aggressive tumor features in Prostate Cancer and urothelial carcinoma of the bladder. However, the role of RING1 in non-small-cell lung cancer (NSCLC) tumorigenesis has never been elucidated. So we aimed at investigating the potential role of RING1 in NSCLC. RING1 expression was evaluated by Immunoblot in 8 paired fresh lung cancer tissues and immunohistochemistry on 69 paraffin-embedded sections from 2006 to 2009. Furthermore, flow-cytometry and RNA interference were performed to analyse the role of RING1 in A549 cells. We showed that the expression level of RING1 was significant increased in lung cancer as compared with the adjacent normal tissue. High expression level of RING1 was associated with TNM stage (P = 0.013), and RING1 was positively related with proliferation marker Ki67 (P < 0.05). Moreover, RING1 knockdown induces growth suppression of human lung cancer cells through G1/S cell cycle phase arrest in vitro. Kaplan-Meier survival curves showed that high expression level of RING1 was associated with poor prognosis (P = 0.03). On the basis of these results, we suggested that RING1 protein expression may be a favorable independent prognostic parameter for non-small cell lung cancer.