Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Humans ; Lung Neoplasms/pathology* ; Adenocarcinoma/pathology* ; Papilloma/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Gene Amplification ; Carrier Proteins ; Cytoskeletal Proteins

Humans ; Carcinoma, Mucoepidermoid/pathology* ; Thyroid Neoplasms/pathology* ; Eosinophilia/pathology*

Humans ; Breast ; Neoplasms, Muscle Tissue/surgery*

Humans ; Sarcoma ; NFATC Transcription Factors ; RNA-Binding Protein EWS

As total mesorectal excision (TME) for rectal cancer is widely carried out in China, lateral ligament of rectum, as an important anatomical structure of the lateral rectum with certain anatomical value and clinical significance, has been the focus of attention. In this paper, by comparing and analyzing the characteristics about ligaments of the abdomen and pelvis, reviewing the membrane anatomy and the theory of primitive gut rotation, and combining clinical observations and histological studies, the author came to a conclusion that lateral ligament of rectum does not exist, but is only a relatively dense space on the rectal side accompanied by numerous tiny nerve plexuses and small blood vessels penetrating through it.
Humans ; Rectum/anatomy & histology* ; Pelvis/anatomy & histology* ; Rectal Neoplasms/surgery* ; Peritoneum ; Collateral Ligaments ; Cognition

Faculty ; Female ; Humans ; Kidney ; Lipids ; Male ; Physical Fitness ; Universities

Occupational noise is one of the most common occupational hazards in the workplace. Long-term exposure to occupational noise could not only lead to the damage of the hearing system, but also may cause a certain impact on the cardiovascular system. Studies have shown that occupational noise exposure was positively associated with cardiovascular diseases, including hypertension, coronary heart disease and myocardial infarction. However, the results of studies on occupational noise exposure and stroke are still controversial. This paper reviews the relationship between occupational noise exposure and hypertension, coronary heart disease, stroke, myocardial infarction by summarizing the epidemiological data of domestic and foreign population in recent years. Our study could provide evidence for the design and implementation of well-designed epidemiological and mechanism studies, and the recognition of the role of occupational noise exposure in the occurrence and development of cardiovascular diseases, so as to better protect workers' health.
Cardiovascular Diseases/etiology* ; Hearing Loss, Noise-Induced ; Humans ; Hypertension/etiology* ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure/adverse effects*

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective: To study the relationship between the age of menarche and the near-term/long-term obesity in adult women. Methods: We analyzed the baseline data of 30 895 women with complete data on menarche and body measurement that was from the China Kadoorie Biobank (CKB) study from 2004 to 2008. The age of menarche was divided into three groups: ≤12, 13-16 and ≥17 years old. Prematurity was set at age ≤12 years. Multivariate logistic regression was used to analyze the effects of menarche age on the near/long-term obesity in female adults. Results: The average menarche age of respondent appeared as (15.64±1.92) years old, with prematurity number as 1 421, accounting for 4.6% of the total numbers. Regarding the postponing of dates of birth, the age of menarche in women showed an advancing tendency. Among all the adult women under study, 803 developed near-term obesity, with the prevalence as 2.6%, while the number of long-term obesity was 3 738, accounting for 12.1%. Refining factors of age, lifestyle, menopausal status, hypertension and diabetes showed that the menarche age was related to the risks of both short-term and long-term obesity in women and the ORs (95%CI) were 2.45 (1.74-3.45) and 1.99 (1.69-2.34), respectively. There was no multiplicative interaction shown between the menarche age and menopausal status on long-term obesity (P=0.324). Conclusion: Premature menarche appeared a risk factor for near-term/long-term obesity in adult females.
Adolescent ; Adult ; Age Factors ; China/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Menarche ; Obesity/epidemiology* ; Risk Factors