A comparison of three-port and four-port Da Vinci robot-assisted thoracoscopic surgery for lung cancer: a retrospective study.

BACKGROUND: At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer. METHODS: 171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups. RESULTS: All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p < 0.001). No significant difference was observed between the two groups in the hospitalization costs (P = 0.664), number or stations of total lymph node dissected (p > 0.05) and postoperative respiratory complications (P > 0.05). CONCLUSIONS: The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.

Targeting macrophagic PIM-1 alleviates osteoarthritis by inhibiting NLRP3 inflammasome activation via suppressing mitochondrial ROS/Cl- efflux signaling pathway.

BACKGROUND: Osteoarthritis (OA), in which macrophage-driven synovitis is considered closely related to cartilage destruction and could occur at any stage, is an inflammatory arthritis. However, there are no effective targets to cure the progression of OA. The NOD-, LRR-,and pyrin domain-containing protein 3 (NLRP3) inflammasome in synovial macrophages participates in the pathological inflammatory process and treatment strategies targeting it are considered to be an effective approach for OA. PIM-1 kinase, as a downstream effector of many cytokine signaling pathways, plays a pro-inflammatory role in inflammatory disease. METHODS: In this study, we evaluated the expression of the PIM-1 and the infiltration of synovial macrophages in the human OA synovium. The effects and mechanism of PIM-1 were investigated in mice and human macrophages stimulated by lipopolysaccharide (LPS) and different agonists such as nigericin, ATP, Monosodium urate (MSU), and Aluminum salt (Alum). The protective effects on chondrocytes were assessed by a modified co-culture system induced by macrophage condition medium (CM). The therapeutic effect in vivo was confirmed by the medial meniscus (DMM)-induced OA in mice. RESULTS: The expression of PIM-1 was increased in the human OA synovium which was accompanied by the infiltration of synovial macrophages. In vitro experiments, suppression of PIM-1 by SMI-4a, a specific inhibitor, rapidly inhibited the NLRP3 inflammasome activation in mice and human macrophages and gasdermin-D (GSDME)-mediated pyroptosis. Furthermore, PIM-1 inhibition specifically blocked the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization in the assembly stage. Mechanistically, PIM-1 inhibition alleviated the mitochondrial reactive oxygen species (ROS)/chloride intracellular channel proteins (CLICs)-dependent Cl- efflux signaling pathway, which eventually resulted in the blockade of the ASC oligomerization and NLRP3 inflammasome activation. Furthermore, PIM-1 suppression showed chondroprotective effects in the modified co-culture system. Finally, SMI-4a significantly suppressed the expression of PIM-1 in the synovium and reduced the synovitis scores and the Osteoarthritis Research Society International (OARSI) score in the DMM-induced OA model. CONCLUSIONS: Therefore, PIM-1 represented a new class of promising targets as a treatment of OA to target these mechanisms in macrophages and widened the road to therapeutic strategies for OA.

Metabolism-related long non-coding RNA in the stomach cancer associated with 11 AMMLs predictive nomograms for OS in STAD.

Background: The metabolic processes involving amino acids are intimately linked to the onset and progression of cancer. Long non-coding RNAs (LncRNAs) perform an indispensable function in the modulation of metabolic processes as well as the advancement of tumors. Non-etheless, research into the role that amino acid metabolism-related LncRNAs (AMMLs) might play in predicting the prognosis of stomach adenocarcinoma (STAD) has not been done. Therefore, This study sought to design a model for AMMLs to predict STAD-related prognosis and elucidate their immune properties and molecular mechanisms. Methods: The STAD RNA-seq data in the TCGA-STAD dataset were randomized into the training and validation groups in a 1:1 ratio, and models were constructed and validated respectively. In the molecular signature database, This study screened for genes involved in amino acid metabolism. AMMLs were obtained by Pearson's correlation analysis, and predictive risk characteristics were established using least absolute shrinkage and selection operator (LASSO) regression, univariate Cox analysis, and multivariate Cox analysis. Subsequently, the immune and molecular profiles of high- and low-risk patients and the benefit of the drug were examined. Results: Eleven AMMLs (LINC01697, LINC00460, LINC00592, MIR548XHG, LINC02728, RBAKDN, LINCOG, LINC00449, LINC01819, and UBE2R2-AS1) were used to develop a prognostic model. Moreover, high-risk individuals had worse overall survival (OS) than low-risk patients in the validation and comprehensive groups. A high-risk score was associated with cancer metastasis as well as angiogenic pathways and high infiltration of tumor-associated fibroblasts, Treg cells, and M2 macrophages; suppressed immune responses; and a more aggressive phenotype. Conclusion: This study identified a risk signal associated with 11 AMMLs and established predictive nomograms for OS in STAD. These findings will help us personalize treatment for gastric cancer patients.

Robotic-assisted pulmonary lobectomy with lung cancer in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis (SIT) is a relatively rare congenital abnormality in which the major thoracic and abdominal visceral organs are reversed from their usual positions. In patients with SIT and bronchial carcinoma, surgical difficulty increases sharply. It has been reported that the video-assisted thoracic surgery (VATS) still poses the operator to a challenge situation. The similarity of surgical positions and the flexibility of the mechanical arm in robotic surgery, may be beneficial to SIT patients due to reducing technical difficulties. Here, we present a first case of SIT patient with lung cancer, in which Da Vinci robot-assisted thoracic surgery (RATS) was performed successfully. CASE PRESENTATION: A 66-year old patient, previously diagnosed with SIT since childhood, came to our hospital with two pulmonary nodules in his left lung field. The bigger one had increased somewhat for the last 2 years of follow-up. Software Mimics was preoperatively carried out to analyze anatomical variations. RATS was conducted to complete left upper lobectomy and left middle wedge resection. The patient had no intraoperative complications and was discharged day 5 after the operation. CONCLUSIONS: This is the first report of a successful robot-assisted lung cancer resection in a patient with SIT. In such challenging cases as lung cancer and rare anomaly as SIT, RATS is more advantageous and suitable than VATS with the help of software Mimics utilized for 3D reconstruction, which can identify the anatomical abnormalities and facilitate the surgical procedures.

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments.

Hepatic ischemia/reperfusion injury (IRI) is mainly characterized by high activation of immune inflammatory responses and metabolic responses. Understanding the molecular and metabolic mechanisms underlying development of hepatic IRI is critical for developing effective therapies for hepatic IRI. Recent advances in research have improved our understanding of the pathogenesis of IRI. During IRI, hepatocyte injury and inflammatory responses are mediated by crosstalk between the immune cells and metabolic components. This crosstalk can be targeted to treat or reverse hepatic IRI. Thus, a deep understanding of hepatic microenvironment, especially the immune and metabolic responses, can reveal new therapeutic opportunities for hepatic IRI. In this review, we describe important cells in the liver microenvironment (especially non-parenchymal cells) that regulate immune inflammatory responses. The role of metabolic components in the diagnosis and prevention of hepatic IRI are discussed. Furthermore, recent updated therapeutic strategies based on the hepatic microenvironment, including immune cells and metabolic components, are highlighted.

Insights From the Analysis of Clinicopathological and Prognostic Factors in Patients With Gallbladder Cancer.

Aims: To investigate the clinical efficacy and prognostic factors of primary gallbladder cancer (GBC) treated by radical surgery. Methods: The clinical and pathological data of 168 patients with primary gallbladder cancer admitted and treated in the Third Affiliated Hospital of Soochow University from January 1st, 2010 to December 31st, 2018 were analyzed retrospectively. Kaplan Meier method was used to draw the survival curve and evaluate the survival rate. Chi-square test was used for univariate analysis and binary logistic regression was used for multivariate analysis. Results: 94 cases showed symptoms of abdominal pain and abdominal distension. 7 cases showed symptoms of fatigue and weight loss. Jaundice occurred in 10 patients. Fever occurred in 6 patients. 51 patients had no symptoms at all. The median survival time of 168 patients was 35.0 (1.0 ~ 142.0) months. The overall 1-, 2- and 3-year cumulative survival rates were 69.6%, 55.4% and 48.8% respectively. The univariate analysis indicated that preoperative bilirubin, tumor size, tumor location, pathological type, degree of differentiation, liver invasion, nerve invasion, vascular invasion, surgical margin, filtration depth and N staging were significant factors influencing prognosis of patients with primary GBC (P<0.05). The results of multivariate analysis demonstrated that degree of differentiation, nerve invasion, filtration depth and N staging were independent risk factors for prognosis of patients with primary GBC (P<0.05). Conclusion: Patients with risk factors of gallbladder cancer should be more active in early cholecystectomy to avoid the malignant transformation of benign diseases. Degree of differentiation, nerve invasion, filtration depth and N staging were important factors for poor prognosis of patients with primary GBC. For T4 staging patients, preoperative evaluation should be more comprehensive, and patients and surgeons should be more prudent in adopting appropriate clinical treatment. The primary purpose should be prolonging the survival time and improving the quality of life.

Primary Suture of the Common Bile Duct: Continuous or Interrupted?

Objective: To compare the effectiveness and safety of continuous suture and interrupted suture in Laparoscopic Common Bile Duct Exploration (LCBDE) for choledocholithiasis. Materials and Methods: The data of 125 patients with choledocholithiasis treated with LCBDE in our department from January 2017 to January 2019 were retrospectively collected and divided into two subgroups: the continuous suture group (n = 56) and the interrupted suture group (n = 69). The operation duration, time to suture, intraoperative blood loss, extubation time, hospital stay, total hospitalization expenses, preoperative and postoperative diameters of the common bile duct (CBD), and the occurrence rate of postoperative complications were all compared between the two groups. Results: The operative duration, time to suture, and intraoperative blood loss in the continuous suture group were less compared with those in the interrupted suture group (P < .05). There was no statistical significance between the 2 groups considering extubation time, hospital stay, total hospitalization expenses, and the occurrence rate of postoperative complications (P > .05). The postoperative CBD diameters in both groups were significantly larger than the preoperative CBD diameters (P < .05). Conclusions: The continuous suture technique shortened the operative duration, time to suture, and reduced intraoperative blood loss. It proves to be an effective and safe method in patients diagnosed with CBD stones.

Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF, PI3K/Akt and Ki-67/CD31.

This study aimed to investigate the anti-tumour effect of apatinib on extensive-stage small cell lung cancer (SCLC) and elucidate the associated mechanisms. NCI-H345 cells were selected as model cells because of high expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and phosphorylated-VEGFR2 (pVEGFR2). Cells were exposed to recombinant human VEGF (rhVEGF) and apatinib. Cells were then divided into eight groups, namely, control, rhVEGF, apatinib, rhVEGF+apatinib, serum-free medium (SM), SM+rhVEGF, SM+apatinib and SM+rhVEGF+apatinib. In comparison with the control group, cell proliferation in vitro in apatinib, SM, SM+apatinib and SM+rhVEGF+apatinib groups was inhibited, particularly in SM+apatinib group. The effect of apatinib on tumour growth in vivo was investigated using a mouse xenograft tumour model. In comparison with the control group, tumour sizes were reduced in apatinib-treated group on days 34 and 37. Immunohistochemical and immunofluorescence staining revealed that VEGF, pVEGFR2, PI3K, AKT, p-ERK1/2, Ki-67 and CD31 in the tumour cells of apatinib-treated group were downregulated compared with control group. Haematoxylin and eosin staining revealed that apatinib promoted the necrosis of SCLC cells in vivo. In conclusion, apatinib inhibited the growth of SCLC cells by downregulating the expression of VEGF, pVEGFR2, p-PI3K, p-AKT, p-ERK1/2, Ki-67 and CD31.

GPER-Induced ERK Signaling Decreases Cell Viability of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Effective biomarkers and specific therapeutic targets for HCC are therefore urgently needed. G protein-coupled estrogen receptor (GPER) plays a crucial role in numerous cancer types; however, its functions in HCC require further exploration. In the present study, we found a remarkable difference in GPER staining between tumor tissue (100/141, 70.9%) and matched non-tumor tissue (27/30, 90.0%). Compared with the GPER-negative patients, the GPER-positive patients with HCC were closely associated with female sex, negative hepatitis B surface antigen, small tumor size, low serum alpha fetoprotein level, and longer overall survival. Treatment with GPER-specific agonist G1 led to the sustained and transient activation of the EGFR/ERK and EGFR/AKT signaling pathways, respectively, in the HCC cell lines HCCLM3 and SMMC-7721, which express high levels of GPER. Interestingly, G1-induced EGFR/ERK signaling, rather than EGFR/AKT signaling mediated by GPER, was involved in decreasing cell viability by blocking cell cycle progression, thereby promoting apoptosis and inhibiting cell growth. Clinical analysis indicated that simultaneous high expression of GPER and phosphorylated-ERK (p-ERK) predicted improved prognosis for HCC. Finally, the activation of GPER/ERK signaling remarkably suppressed tumor growth in an HCC xenograft model, and this result was consistent with the in vitro data. Our findings suggest that specific activation of the GPER/ERK axis may serve as a novel tumor-suppressive mechanism and that this axis could be a therapeutic target for HCC.

MiR-331-3p Inhibition of the Hepatocellular Carcinoma (HCC) Bel-7402 Cell Line by Down-Regulation of E2F1.

MicroRNAs play an important role in cell proliferation and migration in hepatocellular carcinoma (HCC). In this study, the expression of MiR-331-3p in the liver cancer tissues of 116 patients, and in one normal (HL-7702) and five HCC cell lines (HepG2, SMMC-7721, Bel-7402, QGY-7701 and QGY-7703) was determined by qRT-PCR. Results indicated that MiR-331-3p was significantly repressed in HCC patients and in HCC cell lines, especially in the Bel-7402 cells when compared to normal liver tissue and the normal hepatocyte line, HL-7702. Therefore, artificial MiR-331-3p mimic computationally targeting E2F1 and anti-sense MiR-331-3p inhibitor were designed and used to transfect the Bel-7402 lines. Stable expression and significant inhibition of MiR-331-3p, with clear changes in cell morphology, proliferation and motility, were detected in Bel-7402 cells transfected with MiR-331-3p mimic or inhibitor, respectively. As E2F1 was computationally recognized as the target of MiR-331-3p, the expression of E2F1 in transfected Bel-7402 cells was analyzed by qRT-PCR and Western blotting. Results showed a strong inhibition of E2F1 by MiR-331-3p and further promotion of E2F1 by MiR-331-3p inhibitor in transfected Bel-7402 cells. Flow cytometry analysis showed that the cell ratio was restored to S to G0/1 cell number. Inhibition of E2F1 by MiR-331-3p mimic promoted cell proliferation and migration in Bel-7402. These results demonstrated that MiR-331-3p down-regulated E2F1 to promote cell proliferation and migration in HCC.

Antitumor activity of chloroquine in combination with Cisplatin in human gastric cancer xenografts.

PURPOSE: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. MATERIALS AND METHODS: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. RESULTS: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). CONCLUSIONS: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

[Clinical analysis of CT guided unilateral PVP for the treatment of osteoporotic vertebral compression fracture in senile patients].

OBJECTIVE: To evaluate the therapeutic effect and security of CT guided unilateral percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in senile patients. METHODS: From April 2009 to June 2010, 26 patients undergoing CT guided unilateral percutaneous vertebroplasty were analyzed retrospectively. There were 9 males and 17 females,ranging in age from 60 to 85 years with an average of (67.50+/-6.76) years, ranging in course of disease from 2 to 30 days with an average of (8.92+/-4.36) d. The affected segments involved 35 vertebras. The major clinical manifestations of OVCF were lumbar-back pain (especially when turning over or stooping down) and unable to bear. The needle was punctured into vertebral of lesions through unilateral puncture under the CT guidance; and then 3-5 ml bone cement was injected into vertebral. Antibiotic was used 3 days to prevent postoperative infections. Postoperative complications were observed after operation, such as local leakage of bone cement, penetrating spinal cord and/or segmental spinal nerve injuries and pulmonary embolism. X-ray was used to measure the height of anterior, middle and exterior of vertebral before and after treatment. A visual analog scale (VAS) scoring was applied to evaluate pain score preoperative, 48 hours postoperative and the terminal follow-up. RESULTS: Twenty-six patients achieved success in punctuation without serious complications. Local leakage of bone cement occurred in 6 cases, but without clinical symptoms or signs. One patient suffered from acute intraoperative reactions to bone cement and relieved by 5 mg dexamethasone and oxygen. All patients were followed up for 6 to 12 months [averaged (8.4+/-1.6) months]. The postoperative vertebrae height was higher than preoperative,but there was no statistical difference between postoperative and preoperative (P>0.05). Preoperative VAS scores was 7.63+/-0.92, postoperative score was 3.00+/-1.09, the final follow-up score was 2.38+/-1.17; there was significant difference between preoperative and postoperative at 48 hours (P<0.05), but there was no statistical difference between final follow-up and postoperative at 48 hours (P>0.05). CONCLUSION: Unilateral PVP under CT guided can increase the vertebral strength and stabilize vertebral body,and the procedure is a safe and effective method for OVCF in elderly patients.

E-cadherin and calretinin as immunocytochemical markers to differentiate malignant from benign serous effusions.

AIM: To investigate the expressions of E-cadherin and calretinin in exfoliated cells of serous effusions and evaluate their values in distinguishing malignant effusions from benign ones. METHODS: Fresh serous effusion specimens were centrifuged and exfoliated cells were collected. Cells were then processed with a standardized procedure, including paraformaldehyde fixation, BSA-PBS solution washing and smears preparation. E-cadherin and calretinin were detected by immunocytochemistry (ICC). RESULTS: In the exfoliated cells of serous effusions, most of carcinoma cells only expressed E-cadherin, and most of mesothelial cells only expressed calretinin, and benign cells (lymphocytes and granulocytes) did not express either of them. For E-cadherin, 85.7% (30/35) of malignant effusions and 8.1% (3/37) of benign fluids were ICC-positive (P<0.001). The sensitivity of E-cadherin ICC in the diagnosis of malignant effusions was 85.7%, specificity 91.9%, and diagnostic rate 88.9%. For calretinin, 94.6% (35/37) of benign effusions and 11.4% (4/35) of malignant effusions were ICC-positive (P<0.001). The sensitivity of calretinin ICC in the diagnosis of benign effusions was 94.6%, specificity 88.6%, and diagnostic rate 91.7%. For diagnosis of benign and malignant effusions by combining E-cadherin ICC and calretinin ICC, the specificities were up to 100% and 97.1%, respectively. CONCLUSION: E-cadherin ICC and calretinin ICC are sensitive and specific in differential diagnosis of benign and malignant serous effusion specimens and specificities are evidently improved when both markers are combined.