Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

Hepatectomy is the most effective method for the treatment of liver cancer. Asso-ciating liver partition and portal vein ligation for staged hepatectomy (ALPPS) provides resectable opportunities for patients with unresectable or borderline resectable liver cancer. Traditional ALPPS procedures involve a short interval between two stages of the surgery, leading to a higher incidence of perioperative complications and mortality. The authors present a case of two-stage hepatectomy. Initially, laparoscopic ligation of the right hepatic artery and portal vein was performed. To prevent tumor progression after the first stage of surgery, combined immunotherapy and targeted therapy were administered. Three months later, a successful right hemihepatectomy was performed. Postoperative histopathological examination revealed hepatocellular carcinoma with extensive tumor necrosis. A 15-month follow-up showed no tumor recurrence. This indicated that two-stage hepatectomy including simultaneous ligation of the hepatic artery and portal vein, combined with two-stage hepatectomy plus immunotherapy and targeted therapy, showed considerable promise for borderline resectable liver cancer.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer.Methods:The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers.Results:MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression ( P<0.05, respectively). Combined positive score (CPS) was an independent risk factor ( P=0.026, HR=8.385, 95% CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion ( P=0.007) and infiltration depth ( P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site ( P=0.45). Conclusions:MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.

BACKGROUND: Thoracoscopic surgery has gradually become the major procedure for lung cancer surgery in our department. Its characteristics are minimal trauma and quick recovery, which make approximately 90% of patients discharge from the hospital after surgery. However, the postoperative complications still happen now and then. We analyzed the patients who had been hospitalized for longer than 7 days after thoracoscopic lung cancer surgery, aiming to summarize the types and risk factors of complications, and improve postoperative safety of patients. METHODS: The data were come from the prospective database of Thoracic Surgery Unit One in Peking Cancer Hospital, and patients that underwent thoracoscopic pulmonary surgery between Jan. 2010 and Dec. 2014 with length of stay more than 7 days were included in the study. The classifications of the complications were investigated and graded as mild or severe complications according to modified Claviengrading, the relationship between clinical factors and degrees of complications was also analyzed. RESULTS: The hospitalization of 115 cases were longer than 7 days after surgery, accounting for 10.3% (115/1,112) of the whole patients that underwent surgery during the same period. Eighty-one cases had mild complications, accounting for 7.3% (81/1,112) of the whole cases that underwent surgery during the same period and 70.4% (81/115) of the cases with prolonged length of stay; the proportions of severe complications in both groups were 3.1% (34/1,112) and 29.6% (34/115), respectively; and the proportions of complications that caused perioperative deaths were 0.18% (2/1112) and 1.7% (2/115), respectively. Among all the postoperative complications, the most common was air leakage for more than 5 days after surgery, with a total of 20 cases (1.8% and 17.4%). The other common complications were: atelectasis (19 cases, 1.7% and 16.5%), pulmonary infection (18 cases, 1.6% and 15.7%), etc. The less common complications was bronchopleural fistula (4 cases, 0.36% and 3.5%) with very high risk, and 2 cases died perioperatively due to the combination of acute respiratory distresssyndrome (ARDS). In the clinical factors, only preoperative low pulmonary function (FEV1%<70%) was the potential risk factor for postoperative severe complications (45.8% vs 23.6%, P=0.038). There was no significant difference either regarding the 5 year disease free survival or the 5 year overall survival between mild complication group and severe complication group, with 5 year DFS being 52.2% and 51.9%, respectively (P=0.894) , and 5 year overall survival being 64.0% and 53.5%, respectively (P=0.673). CONCLUSIONS Continuous postoperative air leakage, atelectasis and pulmonary infections were the major causes for prolonged hospitalization after thoracoscopic surgery for lung cancer, and bronchopleural fistula was the most perilous complications. Patients with low preoperative pulmonary function were more likely to have severe postoperative complication, however, this would not influence the long term survival of the patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Hospitalization ; Humans ; Length of Stay ; Lung Neoplasms ; complications ; surgery ; therapy ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Postoperative Period ; Prospective Studies ; Thoracic Surgery, Video-Assisted

BACKGROUND: Currently, there is no consensus on the follow-up strategy (follow-up time interval and content) of non-small cell lung cancer (NSCLC) in the world, and the relevant clinical evidence is also very limited. In this study, we aimed to summarize the recurrence/metastasis sites and timings of stage I NSCLC patients based on their follow-up data, aiming to provide a basis of follow-up time interval and content for this group of patients. METHODS: We retrospectively analyzed the 416 stage I NSCLC patients that underwent continuous anatomic lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database. According to the recurrence/metastasis sites and timings, the long term follow-up time interval and content were explored. RESULTS: The 5-yr disease free survival (DFS) and overall survival (OS) in the whole group were 82.4% and 85.4%, respectively. There were 76 cases (18.3%) had recurrence/metastasis during follow-up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%), followed by brain metastasis (20 cases, 4.8%), bone metastasis (12 cases, 2.9%), and mediastinal lymph node metastasis (12 cases, 2.9%). Among the factors that could influence recurrence/metastasis, patients with pT2a suffered from a higher recurrence/metastasis rate compared to patients with pT1 (P=0.006), with 5-yr DFS being 73.8% and 87.3%, respectively (P=0.002), and the 5-yr OS being 77.7% and 90.3%, respectively (P=0.011). CONCLUSIONS The commonest recurrence/metastasis sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that between 3 years and 5 years. The follow-up frequencies and content within 2 years could be adjusted according to T stages.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymph Nodes ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Prospective Studies ; Retrospective Studies ; Young Adult

Objective: To discuss the effect and safety of continuous pumping for home enteral nutrition after esophagectomy. Methods: The current study retrospectively analyzed the esophageal cancer patients who underwent transthoracic esophagectomy between January 2017 and November 2017 at First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute. There were totally 108 cases, including 88 males and 20 females, with an average age of 62 years. The patients were divided into pump feeding group (n=56) and traditional tube feeding group (n=52). The postoperative short-term safety, weight maintenance, enteral nutrition tolerance and nutritional support complete rate of the 2 groups were compared by χ² test, Fisher exact test and t test, respectively. Results: Compared with traditional tube feeding group, the patient safety in pumping feeding group was significantly better, with complications within 2 months after discharge were 11/52 and 4/56 respectively (χ²=2.393, P=0.035); the weight maintenance was significantly better, the weight loss within 4 weeks after discharge were 3.90 kg and 0.13 kg, respectively (t=7.720, P=0.000); the general enteral complications were significantly lower (26/52 vs. 5/56, χ²=22.225, P=0.000), the nutritional support complete rate was significantly higher (23/52 vs. 55/56, χ²=39.167, P=0.000). Conclusions Continuous pump feeding enteral nutrition support after discharge postoperatively could help improve patient safety after discharge, which is better for weight maintenance of the patients. Pump feeding could also enhance tolerability of tube feeding and ensure the effective accomplishment of nutritional support.