[CD103+CD8+T cells combined with neutrophil-to-lymphocyte ratio predict response to neoadjuvant chemoimmunotherapy in advanced oral squamous cell carcinoma].

Objective: To investigate the relationship between the expression of CD103+CD8+T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods: Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103+CD8+T cells and the efficacy of NACI. CD103+CD8+T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103+CD8+T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It's effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results: The density of CD103+CD8+T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103+CD8+T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm2 and 21.63(4.91, 71.92) pcs/mm2 respectively, with statistically significant differences(U=52.00, P=0.012). CD103+CD8+T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII (P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 (P=0.009, 95%CI: 0.5715-0.9910), 0.671 (P=0.105, 95%CI: 0.467-0.881), 0.679 (P=0.020 95%CI: 0.549-0.951), 0.750 (P=0.096, 95%CI: 0.461-0.896), respectively. The AUC for CD103+CD8+T cells alone was 0.861 (P=0.013, 95%CI: 0.585-0.950), and the AUC of combining CD103+CD8+T cells with NLR was 0.896 (P=0.025, 95%CI: 0.454-0.938). Conclusions: The density of CD103+CD8+T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103+CD8+T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103+CD8+T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.

[Molecular targeted therapy strategy and clinical research progress in pancreatic ductal adenocarcinoma].

The incidence of pancreatic ductal adenocarcinoma(PDAC) is increasing year by year among digestive system tumors.It has a high degree of malignancy and a poor prognosis.Its five-year survival rate is less than 8%.Traditional radiotherapy and chemotherapy are not sensitive to pancreatic cancer,so finding a new drug is the future hope for pancreatic cancer.In recent years,molecular targeted therapy has made obvious progress in diseases such as hematological malignancies,non-small cell lung cancer and melanoma,and a large number of targets have been tried in pancreatic cancer, for example, gene mutation targets, important signaling pathway targets, receptor targets, etc. The use of these targeted drugs alone or in combination has shown good results in preclinical models and some clinical trials, and some treatment have been standardized for patients with pancreatic cancer, while other options that have not yet been tested in large-scale clinical trials also offer a variety of potential possibilities for future targeted treatments for pancreatic cancer.

[Comparison of single incision robot-assisted laparoscopic radical prostatectomy with and without extraperitoneal special channel device].

Objective: To compare the clinical effects of single-incision robot-assisted laparoscopic radical prostatectomy (RARP) with and without extraperitoneal special channel device. Methods: The clinical data of 70 patients who had undergone RARP in the Robotic Minimally Invasive Surgery Center of Sichuan Provincial People's Hospital from September 2020 to February 2021 were analyzed retrospectively, including 29 cases who were operated on without special channel device (group A) and 41 cases with special channel device (group B). All operations were performed by robot-assisted single-incision retrograde bladder neck exfoliation via extraperitoneal approach in patients by the same operator. The operation time, intraoperative blood loss, the bladder neck urethral anastomosis time, postoperative hospital stay, postoperative exhaust time, positive rate of incisal margin, indwelling time of urinary catheter, retention rate of postoperative erectile function, satisfaction rate of immediate postoperative urine control, positive rate of postoperative lymph node pathology, incision length, treatment cost and the rate of prostate specific antigen (PSA)lower than 0.2 µg/L at 6 weeks after operation were compared between the two groups. Results: All 70 cases were operated successfully. The difference of age[ (68.9±3.9) vs (69.4±5.4) years], preoperative PSA level[14.1(6.3, 19.8)vs13.7(5.8, 18.1)µg/L], prostate volume[44.8(30.7,172.6)vs 56.3(40.9,163.4)ml ] of the two groups was not statistically significant(all P>0.05). The difference of operation time [ (59.1±18.5) vs (59.6±18.0) min ], intraoperative blood loss [93(66,198)vs 95(68,203) ml ], bladder neck urethral anastomosis time [ (12.6±1.3) vs (13.7±2.8) min ], postoperative hospital stay [ (8.1±2.3) vs (9.1±1.3) d], postoperative exhaust time [ (1.4±0.6) vs (1.3±0.6) d], positive rate of incisal margin (20.7% vs 19.5%), indwelling time of the urinary catheter after operation [ (6.8±1.5) vs (7.1±2.0) d ], the retention rate of postoperative erectile function (31.0% vs 27.0%), the satisfaction rate of immediate postoperative urine control (79.3% vs 75.6%), the positive rate of postoperative lymph node pathology (17.2% vs 14.6%), the length of incision [ (5.1±0.5) vs (6.1±0.4) cm ], the rate of PSA lower than 0.2 µg/L at 6 weeks after operation (86.2% vs 83.0%) of the two groups was not statistically significant(all P>0.05). The operation cost of group A[(62 000±4 000) yuan]was lower than group B[(68 000±4 000) yuan] (P<0.05). Conclusion: Extraperitoneal non-special channel device single-incision RARP is safe and feasible.

[Characteristics of pancreatic ductal adenocarcinoma immune microenvironment and related immunotherapy strategies].

Pancreatic ductal adenocarcinoma is one of the common malignant tumors of the digestive tract. It has the characteristics of strong occlusion, aggressiveness, easy metastasis, and resistance to radiotherapy and chemotherapy. Therefore, its five-year survival rate is extremely low, with a rate of less than 8%. Looking for a new treatment is an urgent need to improve the prognosis of pancreatic ductal adenocarcinoma. In recent years, a large number of clinical trials have been carried out, such as immune checkpoint inhibitors, monoclonal antibodies to important antigens, and immune cell therapy. However, it is disappointing that no satisfactory clinical benefits have been achieved. The special microenvironment of pancreatic cancer nests makes immunotherapy not as effective as other malignant tumors. This article introduces the characteristics of the suppressive immune microenvironment of pancreatic cancer and the latest clinical studies of different types of immunotherapy at home and abroad, and analyzes the mechanisms and potentials of combined treatment based on the characteristics of the immune microenvironment.

[Problems and strategies in clinical application of associating liver partition and portal vein ligation for staged hepatectomy].

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can speed up the regeneration of future liver remnant (FLR) in short period of time, and offer a chance for surgical resection for patients without sufficient FLR. However, ALPPS still remains controversy due to its high perioperative morbidity and mortality, as well as the uncertain long-term oncological benefits. How to solve these problems is the key to ensure the safety of surgery.This article focus on the indication selection, liver function reserve evaluation and timing to perform the second stage surgery, surgical mode evolution and comparison with portal venous embolization/portal venous ligation+two-stage hepatectomy.

[The value of Gd-EOB-DTPA-enhanced MRI in patients with major resection of liver cancer].

Objective: To investigate the value of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and predicting the risk of post-hepatoectomy liver failure in patients with major resection of liver cancer. Methods: A total number of 212 patients were included from June 2016 to June 2019 at Department of General Surgery, Peking University Third Hospital with a retrospectively collected data.All patients underwent Gd-EOB-DTPA-enhanced MRI for diagnosis and preoperative evaluation of liver function.There were 135 males and 77 females, with age of (63.1±10.3) years old (range: 18 to 86 years old) . Relative enhancement ratio (RER) of the region of interest on Gd-EOB-DTPA-enhanced MRI was acquired by two independent researcher and then conducted the comparison of RER among the patients with or without post-hepatoectomy liver failure (PHLF) .Preoperative evaluation demonstrated that 141 cases infected by hepatitis virus, 128 cases with hepatitis B alone and 11 cases with hepatitis C alone, 2 cases had both of hepatitis B and C, and all patients were grade A judged by Child-Pugh score. The relationship between RER and PHLF was evaluated by Pearson correlation analysis and the diagnostic value of RER in predicting PHLF was test by receiver operating characteristic curve. Results: PHLF occurred in 42 patients according to ISGLS standard. Among them, 31 cases had level A liver failure, 9 cases had level B liver failure and 2 had level C failure. There was a significant correlation between RER and overall level of PHLF and RER was also significantly associated with severe B to C level of PHLF (P<0.05) .The further receiver operating characteristics curve analysis showed that the diagnostic accuracy of RER on overall PHLF was 0.818 (sensitivity 72.9%, specificity 83.3%, cut-off value 73.5%, 95%CI: 0.75 to 0.887) and on severe PHLF was 0.924 (sensitivity 97.0%, specificity 90.9%, cut-off value: 61.5%, 95%CI: 0.79 to 0.90) . Conclusion: For patients who planned to undergo major resection of liver cancer, preoperative Gd-EOB-DTPA-enhanced MRI can help with the assessment of liver function and predicting the risk for post-hepatectomy liver failure.

[Treatment strategies of pancreatic neuroendocrine neoplasms with liver metastases].

Liver metastases is the most common distant metastases of pancreatic neuroendocrine neoplasms, and it is also one of the main factors affecting the prognosis of patients. With the development of treatment technology and the rise of a multidisciplinary treatment model, the treatment plan for patients with liver metastases has gradually evolved into a comprehensive treatment plan including surgery, intervention, medicine, and radiation therapy. Radical surgery is still the only treatment currently available to cure patients with pancreatic neuroendocrine tumors and liver metastases. Very few selected patients can also benefit from liver transplantation. For most patients who are unable to undergo surgery can choose intervention, medicine and radiation therapy which can improve the patient's prognosis to a certain extent. Targeted therapy and immunotherapy have good development prospects, and further research is still needed. With multidisciplinary treatment, individualized treatment can help patients obtain the best treatment results.

Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.