Abstract: Primary liver cancer (PLC) is the first leading cause of immature cancer death in China. Hepatocellular carcinoma (HCC) in China accounts for 93.0% of PLC. Chronic infection with hepatitis B virus (HBV) HCC contributes to 84.4% of HCC. During HBV-induced hepatocarcinogenesis, non-resolving inflammation facilitates viral and host genome mutations via the up-regulated expression of activationinduced cytidine deaminase/APOBEC3s and decreases mutation repair via the down-regulated expression of uracil DNA glycosylase by proinflammatory cytokines such as interleukin-6. The proinflammatory tumor microenvironment (TME) provides necessary conditions for the “mutation-selection-adaptation” evolutionary process of HBV and human hepatocytes and facilitates the retrodifferentiation of mutated hepatic cells. This evolutionary process has two prerequisites: driving somatic mutations and immune-suppressive TME. Cancerpromoting chromosome instability and viral mutations inhibit type I interferon signaling via activating the cyclic GMP-AMP synthase stimulator of interferon genes, induce immune-suppressive inflammation, and recruit immune-suppressive immune cells, including tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, to build immunosuppressive TME. In the TME, the rapid growth of tumor cell-caused hypoxia activates kynurenine metabolism in the HCC tissues by inducing the expression of immune-suppressive inflammatory factors to promote the expression of PD-1 on regulatory T cells forenhanced immunosuppression; it also inhibits the cytotoxicities of CD8+T and natural killer cells and facilitates angiogenesis. The theoretical update of “Cancer Evo-Dev” highlights the direction of cancer prophylaxis and treatment. The treatments targeting angiogenesis significantly inhibit the growth of HCC, increase anti-tumoral immunity, and enhance the efficacy of immunotherapy. The combination of targeted therapy and immunotherapy should be the major therapeutic option for the treatment of advanced liver cancer.

Ovarian cancer has the highest mortality among the three major gynecological malignancies. Peritoneal metastasis, intestinal obstruction and then death is the main outcome pattern of advanced ovarian cancer. Traditional Chinese medicine maintenance treatment of advanced ovarian cancer is effective, but the theoretical basis needs to be further improved. Under the guidance of the membranous Sanjiao theory and combined with clinical experience, this paper traces the origin, focuses the location of membranous Sanjiao of ovarian cancer peritoneal metastasis and the role of membranous Sanjiao dysfunction in the occurrence and metastasis of ovarian cancer. Besides, the paper puts forward that the main strategies for the maintenance treatment of traditional Chinese medicine on ovarian cancer are ordering the Qi movement of Sanjiao, regulating and harmonizing Qi and blood, and clearing away the latent toxin. From the perspective of membranous Sanjiao theory, the theory enriches the traditional Chinese medicine theory of ovarian cancer and provides new ideas for the treatment of ovarian cancer.

Delayed gastric emptying (DGE) is a common complication following upper gastrointestinal surgery, especially following distal gastrectomy and partial pancreaticoduodenectomy (Whipple procedure). Its underlying mechanism remains unclear and needs to be elucidated. Through negative feedback mechanisms, duodenal distension inhibits gastric emptying. In our experience in performing a gastrojejunostomy, we speculate that this mechanism may still exist in the proximal jejunum and is activated by jejunal distension or stretching. There are many surgical factors leading to this mechanism activation. When a jejunal anastomosis is created by a relative large caliber of a circular stapling device, the mucosa may suffer from a circumferential scratch or bruising injury resulting in local inflammation. Afferent loop twisting may also lead to distal duodenum and/or jejunal distension. In addition, a mild/slight tension may exist on the mesenteric side of the gastrojejuostomy, especially when the antecolic route for reconstruction of the gastrojejunostomy has been performed. The inflammatory mucosa may keep the jejunum circumferentially distended, the bowel twist might compromise the lumen patency, and tension on gastrojejuostomy would stretch the jejunal wall. Any of these factors might contribute to the mechanisms of DGE by the negative feedback mechanisms.

Pituitary adenoma is one common type of intracranial tumors, accounting for about 10% of intracranial tumors. Although pituitary adenomas are benign tumors, the complete resection and recurrence prevention remain challengeable due to aggressive growth of tumor, limited equipment conditions and surgical techniques of the surgeon. The proportion of recurrent pituitary adenomas is rising year by year and the difficulty of treatment also increases. This article reviews the diagnosis and treatment of recurrent pituitary adenomas based on the summary data of invasive or recurrent pituitary adenomas cases in our center, including indication for the second transsphenoidal surgery, surgical techniques, and prevention and treatment of postoperative complications, to provide reference for clinicians in this field.

On the basis of the changing tendency in the sense considering tumors as a kind of chronic and systematic disease and the integrating trend of somatic mutation theory with the one of field cancerization, this paper focuses on the limitations of current therapeutic ideas and strategies in head and neck tumors. It also describes the influence of the modern view of oncogenesis for future treatment and the developing drift of therapies in this field. Although most tumors in the head and neck region are solid ones, their tumorogenesis should be considered as the final event of systemic dysfunction under the consideration of holistic view and systems theory. Through reasonable integration of unique advantages derived from various modern therapies at a much higher level of personalized diagnosis and treatment view, patients with head and neck tumors are expected to survive with much better long-term therapeutic effects and much higher quality of life following treatment.

Metabolism reprogramming plays an important role in the process of tumor occurrence and development, and provides the necessary material basis for tumor cells. It can change the metabolic patterns of amino acids, glucose and fatty acids in tumor cells, which is one of the hallmark features of tumors. At present, it is shown that most tumors tend to take advantage of glycolysis for energy resource. In contrast, studies have shown that prostate cancer cells dependent more on the fatty acid oxidation pathway for metabolic reprogramming to obtain energy substances. Therefore, it is of great significance to understand the relation between key enzymes of lipid metabolism and regulatory genes for early diagnosis, targeted treatment and better prognosis of prostate cancer.

Objective To investigate the photodynamic antitumor activity and chemical characteristics of pheophorbide A (PPBa) in vitro. Methods Breast cancer cells (MCF-7), lung cancer cells (A549), cervical cancer cells (HeLa), and three kinds of hepatoma cells (HepG2, hep3B and sk-Hep1) were planted in 96-well plates. The effects of light and dark toxicity, light intensity, and drug concentration on the phototoxicity of PPBa were investigated by MTT, and the uptake of PPBa was observed by Hoechst staining under a confocal microscope. The production of singlet oxygen was observed by flow cytometry and confocal microscopy with the reactive oxygen species detection kit. The photobleaching of PPBa was investigated by measuring the absorbance by a microplate reader according to the luminescence characteristics of PPBa. Results PPBa showed strong phototoxicity and low dark toxicity to six kinds of cancer cells, and IC50 values to cancer cells were as follows: MCF-7: 1.033 μmol/L, A549: 1.911 μmol/L, HeLa: 2.319 μmol/L, HepG2: 2.015 μmol/L, Hep3B: 2.089 μmol/L, sk-Hep1: 2.467 μmol/L. The main uptake site of PPBa was the cytoplasm. The production of singlet oxygen was strongly dependent on the administration concentration, and photobleaching was very low. Conclusion For the six kinds of cancer cells, PPBa has the highest phototoxicity to breast cancer cells (MCF-7), with excellent properties and ideal photosensitizer characteristics.

Objective To evaluate the risk of recurrence or metastasis of breast cancer by LNG-IUS via meta-analysis. Methods We searched literature in the PubMed, Web of Science, Cochrane, EMBASE, CBM, CNKI, VIP, and WanFang database. The retrieval period was from January 2014 to October 2021. Data extraction and quality evaluation were conducted for the included randomized controlled study (RCT) to analyze whether LNG-IUS can increase the risk of recurrence or metastasis of breast cancer. Results A total of 1309 Chinese and English studies were retrieved; 5 RCTs were included in this study, and 446 patients were enrolled. The combined total effect value in the fixed-effect model with RD (95%CI) 0.03(-0.03-0.08), Z=1.05, P=0.29) indicated that the LNG-IUS+tamoxifen group did not increase the risk of recurrence or metastasis of breast cancer compared with the tamoxifen group. The funnel diagram was basically symmetrical, suggesting that the publication bias was small. Conclusion Wearing the LNG-IUS does not increase the risk of relapse or metastasis of breast cancer significantly, and it provides certain safety for patients with breast cancer.

Objective To investigate the expression of m6A methylatransferase ZC3H13 in tissues and peripheral blood of patients with gastric cancer and its application value in gastric cancer. Methods UALCAN and GEPIA databases were used to analyze the expression difference of ZC3H13 in gastric cancer and adjacent normal tissues at transcription level; GEPIA and Kaplan-Meier Plotter databases were used to analyze the correlation between ZC3H13 expression level and OS of gastric cancer patients. ELISA was used to determine the concentration of ZC3H13 in 80 newly-diagnosed gastric cancer patients and 50 healthy controls, and to analyze its relation with clinicopathological data; IHC method was used to detect the expression level of ZC3H13 in 74 cases of cancer tissues and 40 cases of unpaired paracancerous tissues, and to analyze its relation with clinicopathological data. Results The expression of ZC3H13 in gastric cancer tissues was significantly higher than that in adjacent gastric tissues (P<0.05). The positive rate of ZC3H13 protein in gastric cancer tissues was significantly higher than that in adjacent normal tissues (74.3% vs. 52.5%, P<0.05). Serum ZC3H13 concentration in gastric cancer group was significantly higher than that in healthy control group (P<0.05). The expression level of ZC3H13 in gastric cancer tissues and peripheral blood was related to gender, differentiation degree, clinical stage and infiltration depth of gastric cancer (P<0.05). Multivariate analysis showed that ZC3H13 expression was not an independent risk factor for poor prognosis of gastric cancer patients (P>0.05). The AUC was 0.826 (P<0.05), indicating good diagnostic value. The critical value of serum ZC3H13 protein concentration was 4.87 ng/ml, and the sensitivity and specificity of ZC3H13 in the diagnosis of gastric cancer were 98.8% and 50.0%. Conclusion ZC3H13 is highly-expressed in gastric cancer tissues, and the concentration of ZC3H13 protein in peripheral blood is also significantly increased. ZC3H13 may play an important role in the occurrence and development of gastric cancer, and has certain clinical diagnostic value for gastric cancer.

Objective To establish a new N-stage system combining the number of metastatic lymph nodes and the ratio of metastatic lymph nodes for postoperative M0 stage inflammatory breast cancer patients. Methods Based on the data of inflammatory breast cancer patients in the SEER database, the number of metastatic lymph nodes and the ratio of metastatic lymph nodes were calculated. A new N-staging system was established and compared with the 8th edition of AJCC TNM staging system of breast cancer. The nomograph prognostic model was constructed and validated. Results The prediction performance of the new N-staging system for postoperative survival of M0 inflammatory breast cancer patients was better than the traditional N-staging system. The nomograph prognostic model showed an excellent clinical efficacy with a consistency index of 0.711. Conclusion The new N-staging system has good predictive performance for postoperative survival of M0 inflammatory breast cancer patients and can accurately reflect the prognosis.

Objective To analyze the incidence and survival trend of malignant tumors in urban residents of Shenyang from 2011 to 2018. Methods The Shenyang tumor registration report system was used to collect the onset data and survival data of patients with malignant tumor from 2011 to 2018. The crude incidence, age-standardized rate, cumulative rate (0-74 years old), truncated rate (35-64 years old), survival rate, and incidence and survival rank were calculated. The observed survival rate was calculated by the life table method. The expected survival rate and relative survival rate were calculated by EdererⅡmethod. Using Joinpoint 3.5.3 software, the annual percentage change in incidence rate and survival rate (APC%) were calculated. SPSS23.0 software was used for the chi square tests of males and females. Results The crude incidence of malignant tumors in Shenyang, age-standardized incidence rates by Chinese standard population and world standard population were 364.70/10 million, 190.00/10 million and 185.63/10 million, respectively. The cumulative rate (0-74 years old) was 21.17%, and the truncated rate (35-64 years old) was 311.66/10 million in the years 2011-2018. The top five incidence rates of males are lung, colorectal, liver, stomach, and bladder cancer, whereas those of females were breast, lung, colorectal, uterine, and thyroid cancer. The incidence rate of malignant tumors increased in 8 years (P=0.00, P=0.67), and the incidence rate was higher in males than that in females (χ ²=201.63, P<0.05). The 5-year survival rate of malignant tumors was 40.49%, and the relative survival rate was 47.84% from 2011 to 2015. The five survival rates of males were in the order of thyroid, kidney, bladder, colon-rectum, and prostate cancer. The five survival rates of females were in the order of thyroid, breast, uterus, cervix, and colon-rectum cancer. The 5-year survival rate showed an upward trend (APC%=7.41, P=0.04). The survival rate of females was higher than that of males (χ ²=187.62, P<0.05). Conclusion The incidence rate and survival rate of malignant tumor in Shenyang urban residents increase yearly from 2011 to 2018. The incidence rate of males is higher than that of females, and the survival rate of males is lower than that of females. The incidence rate and survival rate of tumors differ much in sequence.

TNBC is a special type of breast cancer with strong aggressiveness and poor prognosis. Chemotherapy is still the main treatment for TNBC, due to poor efficacy of endocrine therapy and targeted therapy. However, TNBC is a kind of heterogeneous disease, so it is urgent to study the precise molecular types and explore new precision treatment. This paper will summarize the results of clinical trials and analyze treatment strategies for TNBC, including surgical treatment, radiotherapy, chemotherapy, targeted therapy and immunotherapy, in order to provide evidence for clinical management.

Theaflavins are a class of natural products extracted from black tea or green tea, with significant anti-tumor effects on gastric cancer, liver cancer, breast cancer and other tumors. Theaflavins were once considered as the new products for anticancer therapy. However, the anti-tumor mechanism of theaflavins involves a variety of biological processes, and the regulation is complex. Therefore, this article summarizes the role of theaflavins in promoting tumor cell apoptosis, inducing tumor cell mitotic arrest and regulating tumor immunity, and reviews the inhibition of tumorigenesis and growth through MAPK, PI3K/AKT, Hedgehog, NF-κB, JAK/STAT and Wnt/β-Catenin signal pathways, in order to provide new ideas for cancer treatment and anti-cancer drug development.

In recent years, with the development of comprehensive tumor therapy, hyperthermia has become one of the important means of cancer treatment. A large number of studies have shown that the removal of tumor cells depends on exogenous treatment methods and the body’s own anti-tumor immune status. Hyperthermia cannot only directly kill tumor cells but also activate the body’s immunity to exhibit an anti-tumor effect. In recent years, with the deepening of tumor research, hyperthermia has been able to create a type I tumor microenvironment with PD-L1 overexpression and enrichment of tumor-infiltrating lymphocytes, complementing the enhancement of immune checkpoint inhibitors. Hyperthermia combined with immunotherapy may offer a new perspective in cancer treatment. The mechanism of tumor hyperthermia and anti-tumor immunity and its clinical application have aroused great interest and become a new research field. This article reviews the relationship between tumor hyperthermia and anti-tumor immunity.

Metal-organic frameworks (MOFs) are mixed porous materials which are composed of metal clusters or ions and organic pillars. Given their channel tunability, high porosity, large specific surface area, and good biocompatibility, MOFs can be combined with various biological macromolecules. In recent years, they have been widely studied in the field of biomedicine, especially in the loading of anti-tumor drugs, showing great application prospects. Multifunctional anti-tumor MOF combined with different therapeutic methods provides a new idea and method for tumor treatment. On the basis of the structure of MOF, this paper introduces the advantages of using MOF to load anti-tumor drugs and reviews the application of MOF in tumor therapy.

Mitochondrial DNA (mt-DNA) is an important carrier of extranuclear genetic information. Recent research results show that mt-DNA is closely related to the occurrence and metastasis of various malignant tumors, and can be used for early diagnosis and targeted therapy of cancer. Therefore, further research on the mechanism of mt-DNA in digestive system malignant tumors has important clinical significance for screening and identifying tumor molecular markers for anti-tumor drug targets, cancer diagnosis and prognosis analysis. This article reviews the research progress on the potential relationship, clinical application and therapeutic
targets of mt-DNA and digestive system malignancies.

The postoperative pathological staging system (pTNM) has become an important reference for the selection of various tumor treatment strategies and prognosis evaluation at a global scale, and is a powerful predictor of the prognosis of a variety of solid tumors, but the prognosis is still different in patients with the same pTNM staging. In recent years, studies have confirmed that the negative lymph nodes count (NLNC) is related to the prognosis of a variety of solid tumors. Higher NLNC can improve the prognosis of cancer patients, and NLNC can reduce staging migration, which is expected to be a supplement to the pTNM staging system. This article reviews the value of NLNC in the prognosis of solid tumors.

Lung cancer is one of the most common malignant tumors. Globally, the incidence and mortality of lung cancer are very high and on the rise. In recent years, immune checkpoint inhibitors (ICIs) have a significant survival advantage in treating advanced NSCLC. However, for NSCLC patients with positive driver genes, ICIs are not effective. But some tumor suppressor genes have varying degrees of impact on immunotherapy through mutations or deletions. Among them, serine/threonine kinase 11 (STK11) gene mutations are closely related to PD-1/PD-L1 ICIs. Studies have found that STK11 mutations are related to reduced immune cell infiltration, low PD-L1 expression and poor response to PD-L1 inhibition. This article reviews the research progress of the correlation between STK11 gene mutation and immunotherapy on NSCLC.

Although targeted, immune and other therapeutic strategies have become the first-line standard therapy for patients with advanced lung cancer, acquired drug resistance is still inevitable in most cases. The advent of antibody-drug conjugates (ADC) provides a new choice. ADC is a new anticancer drug formed by the coupling of targeted anti-tumor monoclonal antibodies and cytotoxic drugs. Compared with chemotherapeutic drugs, ADC has the advantages of high tolerance, accurate target recognition and little effect on non-cancer cells, and has shown good clinical benefits in the treatment of a variety of malignant tumors. This article reviews the application of ADC in advanced non-small cell lung cancer.