BACKGROUND:Fibronectin type Ⅲ domain-containing protein 5(FNDC5)is a muscle factor that can regulate glucose and lipid metabolism,and exert anti-inflammatory,anti-oxidative effects and improvement in insulin resistance.Moreover,FNDC5 could control various cell pyroptosis. OBJECTIVE:To explore the effect and potential mechanism of FNDC5 on macrophage pyroptosis. METHODS:(1)After completing the construction of the lentivirus virus overexpressing FNDC5 or silencing FNDC5,the THP-1 cells were transfected with the lentivirus vector.The result of transfection was detected by the expression of green fluorescence,qPCR,and western blot assay.(2)Phorbol ester induced THP-1 cells to differentiate into macrophages.Oxidized low-density lipoprotein(ox-LDL)was added to induce the cell pyroptosis model.There were six groups,i.e.,NC group,ox-LDL group,ox-LDL+MOCK1 group,ox-LDL+Ov-FNDC5 group,ox-LDL+MOCK2 group,and ox-LDL+shFNDC5 group.(3)The level of cell pyroptosis was evaluated by Hoechst 33342/propidium iodide fluorescence double staining and lactate dehydrogenase release assay.The expression levels of related molecules in THP-1 cells were analyzed by qPCR and western blot assay.The interleukin-18 and interleukin-1β in cell supernatant were detected by ELISA. RESULTS AND CONCLUSION:Compared with the ox-LDL+MOCK1 group,overexpression of FNDC5 significantly reduced the pyroptosis rate of macrophages and the release levels of lactate dehydrogenase,interleukin-1β and interleukin-18,significantly inhibited the mRNA expression of NF-κB p65,NF-κB p50,NLRP3,ASC,Caspase-1,and GSDMD,and significantly inhibited the protein expression of NF-κB p65,NF-κB p50,NLRP3,ASC,cleaved Caspase-1 and GSDMD-N.Compared with the ox-LDL+MOCK2 group,the silence of FNDC5 showed the opposite result.These findings suggest that FNDC5 attenuates pyroptosis in macrophages by inhibiting the NF-κB/NLRP3 pathway.

Objective:To investigate the endorectal ultrasound findings in rectal neuroendocrine neoplasms (R-NEN) and to compare the diagnostic performance of ERUS and MRI for T staging of R-NENs.Methods:The imaging features of 77 confirmed R-NEN cases with different pathological grades in the Sixth Affiliated Hospital, Sun Yat-sen University from August 2015 to August 2021 were retrospectively analyzed and the abilities of ERUS and MRI for T staging of R-NENs were compared.Results:A total of 77 R-NEN patients underwent preoperative ERUS examinations and detected lesions in 62 patients with a detection rate of 80.52%. Among them, 30 cases underwent simultaneous MRI examinations, and detected lesions in 25 cases with a detection rate of 83.33%, without statistical difference between MRI and ERUS ( P>0.05). R-NEN exhibited hypoechoic nodules with rich blood flow in the submucosa on ERUS. Grade G1 and G2 tumors generally had sizes less than 10 mm, clear boundaries, and regular shapes, while G3 was typically large, irregular, poorly defined, and more likely to invade the musculi propria and serous layer. G3 demonstrated a more profound infiltration level, a less defined border, and a larger diameter than G1 and G2, with statistically significant differences (all P<0.05). For T staging, the accuracy of ERUS was 86.67%, and that of MRI was 94.67%, with no statistical difference ( P>0.05). Conclusions:ERUS is effective for detecting R-NEN lesions and useful for tumor grading with comparable performance to MRI, and should be recommended for preoperative evaluation of neuroendocrine tumors.

Objective To investigate the relationship between gene mutation characteristics and immunological markers in patients with small cell lung cancer.Methods From January 2019 to 2020,155 patients with small cell lung cancer were admitted.Gene mutations were detected in these patients using target gene capture and sequencing method.Moreover,the tumor mutational burden(TMB)and expression of PD-L1 in some patients were detected.Results A total of 326 gene mutations were detected in the patients,the most significant of which were TP53 and RB1.Among the 8 genes with mutation frequency higher than 15％,patients with KMT2D,KMT2C,FAT1 and NOTCH1 mutations had higher TMB than those without mutation,and the difference was statistically significant(P＜0.05).Conclusion The most common mutated genes in patients with small cell lung cancer are TP53 and RB1.KMT2D,KMT2C,FAT1 and NOTCH1 may be potential markers for the efficacy of immunotherapy in small cell lung cancer.

Objective:To summarize the characteristics of oral contrast ultrasound in patients with esophageal hiatal hernia (EHH), to screen the diagnostic criteria for EHH diagnosis by oral contrast ultrasound and to evaluate their diagnostic values.Methods:Sixty-one patients who visited the Hernia and Abdominal Wall Surgery Department of the Sixth Affiliated Hospital of Sun Yat-sen University from June 2023 to December 2023 for symptoms of acid reflux, heartburn, belching, recurrent epigastric pain, chest pain, and cough, and who were clinically suspected of EHH and underwent oral contrast ultrasound were retrospectively collected. The internal diameter of the esophageal hiatus, the length of the intraabdominal esophagus (IAEL), the angle of His, the supradiaphragmatic hernia sac, the sign of gastric wall sliding, and the sign of esophageal-gastric ring uplift were recorded by oral contrast ultrasound. All ultrasonographic data were retrospectively analyzed, and the diagnosis of EHH by surgery or with the simultaneous diagnosis of EHH by barium meal examination and gastroscopy were used as the gold standard. The diagnostic criteria of oral contrast ultrasound for EHH were obtained and their diagnostic values were evaluated by ROC curve analysis.Results:The indicators of EHH diagnosed by oral contrast ultrasound were analyzed according to ROC curves as follows: internal diameter of esophageal hiatus >15 mm (AUC=0.913), IAEL≤33 mm (AUC=0.776), angle of His > 90° (AUC=0.735), supradiaphragmatic hernia sac (AUC=0.913), gastric wall sliding sign (AUC=0.827), upward displacement of the esophagogastric ring (AUC=0.721). The diagnostic sensitivity, specificity, accuracy, positive predictive value, negative predictive value, AUC, and 95% CI of the diagnosis of EHH using the internal diameter of the esophageal hiatus >15 mm or the presence of a supradiaphragmatic hernia sac as the diagnostic criterion for the diagnosis of EHH by oral contrast ultrasound were 86.5%, 100%, 88.5%, 100%, 56.3%, 0.933, and 0.838-0.981, respectively. Conclusions:The optimal diagnostic criterion for EHH diagnosis by oral contrast ultrasound is esophageal hiatal internal diameter >15 mm or the presence of supradiaphragmatic hernia sac, which has 100% specificity and positive predictive value. It is recommended to be widely used as a screening test for EHH in the clinic.

Objective    To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods    The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results    After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion    Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.

Objective:To investigate the diagnostic value of ultrasound contrast agent enema (UCAE) for anastomotic leakage (AL) after rectal cancer surgery.Methods:From January 2020 to December 2022, a total of 95 patients with presacral fluid collection after rectal cancer surgery in the Sixth Affiliated Hospital of Sun Yat-sen University who received perineal ultrasound (PNUS) and UCAE were retrospectively selected. Among them, 70 patients (73.3%) were diagnosed with AL.After PNUS scanning, all patients received a diluted ultrasound contrast agent administered through the rectum. Receiver operating characteristic (ROC) curve were used to compare the accuracies of PNUS, UCAE, CT, MRI and water-soluble contrast enema in the diagnosis of AL. Factors that may have impacts on the sensitivity of UCAE were thoroughly analyzed.Results:UCAE improved the consistency (Kappa value: 0.757 vs 0.292, P<0.001) and accuracy (AUC: 0.893 vs 0.693, P<0.001) of PNUS in the diagnosis of AL, and its diagnostic accuracy was comparable to that of CT (AUC 0.807), MRI (AUC 0.811) and water-soluble contrast enema (AUC 0.923) (all P>0.05). For mid-to-high AL (anastomotic stoma distance ≥70 mm) and tiny AL (≤3 mm), the sensitivity of UCAE decreased significantly (anastomotic stoma position: 25.0% vs 85.5%, P=0.001; anastomotic leak diameter: 42.9% vs 87.5%, P=0.002). Conclusions:UCAE can significantly improve the diagnostic accuracy and consistency of PNUS for AL after rectal cancer surgery, and its diagnostic sensitivity is affected by the anastomotic stoma distance and the diameter of the leak.

Objective : To investigate the role of dapagliflozin ( DAPA) in ox⁃LDL⁃induced pyroptosis of human myeloid leukemia monocytes (THP⁃1) derived foam cells . Methods : THP⁃1 ⁃derived foam cell pyroptosis model was constructed by ox⁃LDL⁃induced THP⁃1derived macrophages . The experimental groups were set as follows : the blank control group(NC) , the ox⁃LDL group(ox⁃LDL) , and the drug intervention group(ox⁃LDL + DAPA) . Oil Red Ostaining was used to detect the foam cell levels of macrophages . The cell proliferation and toxicity assay kit was used to detect the effect of DAPA on foam cell viability . Hoechst 33342/propidium iodide(PI) double staining was used to detect THP⁃1 derived foam cell pyroptosis . Cell immunofluorescence double staining was used to detect the effect of DAPA on the expression of pyroptosis key factor Caspase⁃1 in foam cells . The activity of lactate dehydrogenase (LDH) in the cell culture medium was detected using a microplate enzyme⁃linked immunosorbent assay. qRT⁃PCR and Western blot were used to detect the mRNA and protein expression levels of Nod⁃like receptor pyrindomain containing 3 (NLRP3) , cystein⁃containing aspartate⁃specific protease⁃1( Caspase⁃1 ) , apoptosis⁃associated⁃speck⁃like protein containing CARD(ASC) ,gasdermin⁃D (GSDMD) , interleukin(IL) Ⅳ18 and IL⁃1β , respectively . Results : The CCK⁃8 assay indicated that the optimal intervention concentration of DAPA was 10 μmol/L. Oil Red O staining confirmed the successful construction of the THP⁃1 ⁃derived foam cell pyroptosis model . Compared with the blank control group , the expression levels of NLRP3 , Caspase⁃1 , ASC , GSDMD , IL⁃18 , IL⁃1β mRNA and protein significantly increased in ox⁃LDL group(P < 0. 05) , as well as the number of PI⁃positive cells and LDH activity(P < 0. 05) , the fluorescence intensity of Caspase⁃1 and the number of redlipid droplets in the cytoplasm of the cells . However , these effects were significantly reversed after DAPA intervention in the ox⁃LDL + DAPA group(P < 0. 05) . Conclusion DAPA inhibits ox⁃LDL⁃induced pyroptosis in THP⁃1 ⁃derived foam cells .

Surgery is a classic traditional method for the treatment of early-stage esophageal cancer, and it is also recognized as an effective first-choice method in the medical community. With the development of endoscopic technology, esophagus-preserving comprehensive treatment of esophageal cancer has almost the same or even better effects in some aspects in the treatment of early esophageal cancer than surgery. Many clinical guidelines have also recommended it as the first-choice treatment for early esophageal cancer. The room for surgical treatment of esophageal cancer has been further compressed. This article discusses the comprehensive treatment model of esophageal cancer from the perspective of thoracic surgery, aiming to find a new position of thoracic surgery in the treatment of esophageal cancer.

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
Animals ; Colloids ; Crystalloid Solutions/therapeutic use* ; Fluid Therapy ; Glycocalyx ; Humans ; Hydroxyethyl Starch Derivatives ; Isotonic Solutions ; Microcirculation ; Resuscitation

BACKGROUND: Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures. RESULTS: The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation. CONCLUSIONS This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.