Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

Gene mutations and chromosomal aberrations are both genotoxic damage with pathogenic potential. However, due to the different scope and breadth of the genetic material involved, the severity and pathogenicity of the harm in human body differed. The pathogenicity of gene mutations depends on cell type, gene type, tissue- and organ-specificity, and others. Mutations in the same gene also result in different outcomes depended on the type of mutation that occurred. Genetic mutations include silent, missense, and nonsense mutations. Silent mutation, which do not alter the structural function of proteins, are typically non-pathogenic. Missense mutation may be pathogenic if protein function is altered, otherwise they are usually non-pathogenic which are also called neutral mutation. Each cell in the human body selectively expresses a small number of genes. Mutations in silenced genes or noncoding regions are generally non-pathogenic. Therefore, some gene mutations are pathogenic or even fatal, but some are non-pathogenic. If they do cause dlisease, it mainly leads to single-gene diseases. Chromosomal aberrations usually involve large DNA segments or even entire chromosome gains or losses, affecting multiple genes, differentiation states, and gene expression and regulation, often leading to cell death or chromosomal disorders. Chronic refractory diseases such as aging, cancer, hypertension, diabetes, Alzheimer′s disease, and degenerative conditions may not be directly caused by genetic mutations and/or chromosomal aberrations. Instead, they likely result from nuclear damage, disruption of differentiation states, and abnormal gene expression/regulation, leading to impaired DNA transcription and protein synthesis. These diseases represent nuclear dysfunction or insufficiency, namely termed differentiation-collapse degenerative diseases. Gene mutations and chromosomal aberrations are thus often epiphenomena relate to manifestations or consequences of nuclear injury and dysfunction.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

The cell nuclear damage is mainly caused by the radiation and various carcinogenic compounds, the essence of the damage is molecular adhesion fracture and chemical modification. After nuclear damage, the cells whose nuclei may be abnormal in morphology, structure and function, then become a kind of morbid cells or defective cells. The cell nuclear damage can affect gene expression and regulation, leading to dysfunctions or abnormalities of transcription and protein synthesis, which results in aging and induces various chronic refractory diseases, such as hypertension, atherosclerosis, diabetes, Alzheimer's disease, autoimmune diseases, and so on. The cell nuclear damage can also affect the state of cell differentiation and lead to restart of genes related to division and proliferation, thus inducing cancer. The cancer cells are derived from the cells with nuclear abnormalities, and the biological behavior or characteristics of cancer cells (shedding and metastasis, immune tolerance, uncontrolled, loss of contact inhibition, etc.) are derived from cells with nuclear abnormalities. This article reviewed the chronic refractory diseases caused by nuclear damage and their mechanisms, which provided a new idea for occupational health and toxicology research, as well as a new method and strategy for occupational disease prevention and treatment.

The cell nuclear damage is mainly caused by the radiation and various carcinogenic compounds, the essence of the damage is molecular adhesion fracture and chemical modification. After nuclear damage, the cells whose nuclei may be abnormal in morphology, structure and function, then become a kind of morbid cells or defective cells. The cell nuclear damage can affect gene expression and regulation, leading to dysfunctions or abnormalities of transcription and protein synthesis, which results in aging and induces various chronic refractory diseases, such as hypertension, atherosclerosis, diabetes, Alzheimer's disease, autoimmune diseases, and so on. The cell nuclear damage can also affect the state of cell differentiation and lead to restart of genes related to division and proliferation, thus inducing cancer. The cancer cells are derived from the cells with nuclear abnormalities, and the biological behavior or characteristics of cancer cells (shedding and metastasis, immune tolerance, uncontrolled, loss of contact inhibition, etc.) are derived from cells with nuclear abnormalities. This article reviewed the chronic refractory diseases caused by nuclear damage and their mechanisms, which provided a new idea for occupational health and toxicology research, as well as a new method and strategy for occupational disease prevention and treatment.

Objective To simplify and optimize the micronucleus test method. Methods The preparation process of micronucleus test was simplified and optimized. In the improved method, the superfine solution was directly absorbed and discarded after cell culture, and then potassium chloride solution was added for hypotonic treatment. Then pre-fixation, centrifugation. Once the centrifugation was completed, the cells which fixed only once were directly dropped to the slide. Results The background of the slides was clear and the cells were slightly darker, but the observation of cells and micronucleus was not affected. There were a lot of binuclear cells, which can meet the counting requirements. With oil and high magnification, the image wais clearer and the background was cleaner. The cytoplasmic integrity rate, cell stain rate and the average number of cells per high magnification field of cells by the improvement method were significantly increased compared with that by the traditional methods, the probability P values were 0.0051 (χ²=7.8375), 0.0140 (χ²=6.0437) and 0.0025 (t=3.0951), respectively. The rate of micronucleus cells and cells group index had no statistical significance compared with the traditional method, the probability P values were 0.7749 (χ²=0.0817) and 0.5152 (U =0.0000), respectively. Conclusion The new method is more simple, easier to control the test quality, more reliable test results, and save time, manpower and material resources.

Objective to determine the basal levels of several pancreas-related endocrine hormones in patients with chronic pancreatitis.Methods according to inclusion and exclusion criteria,consecutive patients from February 2016 to August 2016 in Department of Gastroenterology,Changhai Hospital,Second Military Medical University and ten healthy control (matched for age and gender) were included.Basal levels of glucagon-like peptide 1,pancreatic polypeptide,Secretin,glucagon,somatostatin between groups of CP vs healthy control,CP with abnormal glycometabolism vs CP with normal glycometabolism and alcoholic CP vs non-alcoholic CP were compared.Results a total of 53 patients with chronic pancreatitis and 8 healthy subjects were included in this study.(1) CP vs healthy controls:the level of secretin in healthy control patients is significant lower than that in CP patients;(2) CP with abnormal glycometabolism vs CP with normal glycometabolism:the level of triglyceride and somatostatin is significant lower than that in CP patients;the prevalence of patients with chronic alcohol consumption and the level of glucagon-like peptide 1 in CP with abnormal glycometabolism is significant higher than that in CP with normal glycometabolism;(3) the prevalence of abnormal glycometabolism in alcoholic CP group is significant higher than that in non-alcoholic CP.The results above are all of statistical significance.Conclusions in addition to dysfunction of islets/3-cells,CP also easily affects the level of other pancreas-related hormones such as secretin,somatostatin and glucagon-like peptide 1.Otherwise,chronic alcohol consumption is also strongly related with abnormal glycometabolism,the mechanism deserves further researches.

Objective To analyze the clinical features of recurrent acute pancreatitis (RAP).Methods The clinical data of patients diagnosed as RAP were collected in Changhai Hospital, the Second Military Medical University between January 2016 to July 2016, and chronic pancreatitis(CP) patients and RAP patients to matching, as control group.A prospective cohort study about the clinical features of RAP and CP was set.The survival analysis model was established by Kaplan-Meier′s method, to calculate the cumulative rate of RAP which progressed into CP.Results The morbidity of male patients was 69.0% in the RAP group(n=100) and 60% in the CP group(n=100).The average first onset age of RAP and CP was 38 and 21 years old, respectively;and the teenagers accounted for 12% and 38.6%.The incidence of diabetes was 49.5% and 9%;and the incidence of fatty diarrhea was 46.6% and 19% of the two groups.The cumulative incidence of CP was 2% within 1 year, 4.6% in 3 years, and 12.4% in 5 years.Conclusions Men has higher morbidity in both RAP group and CP group.RAP patients′ first onset age was older than that of CP.Teenagers had a low incidence in RAP group.The risk of diabetes and fatty diarrhea was lower in RAP group than CP group.A certain proportion of RAP patients can progress to CP.

Objective To analysis the clinical features of dorsal pancreas agenesis ( DPA) and the associated diabetes, pancreatitis and other congenital organ malformations.Methods Chinese databases of Sinomed, CQVIP and CNKI using the term of short pancreas, pancreas agenesis, bulbar pancreas and dorsal pancreas, and English databases of PubMed using the term of dorsal pancreas agenesis, short pancreas and pancreas hypoplasia were searched.The clinical manifestation, pancreatic head characteristics and associations with diabetes, pancreatitis and other congenital organ malformations were analyzed.Results Six related publications from Chinese databases were searched and 21 patients were included with 2 cases excluded.Sixty-one publications from English database were searched and 71 patients were included.Thus, a total of 91 patients with DPA were analyzed.Abdominal pain was the most common manifestation, which was reported by 61.5% of the patients. 15.3% patients were identified during regular physical examination. Other manifestations including jaundice, fatigue, abdominal discomfort and diabetes were rare.After removing cases with insufficient information, 39 patients (61.9%) carried abnormal pancreatic head.Prevalence of diabetes or impaired glucose tolerance was 56.7% and the percentage of insulin-dependent diabetes in patients with abnormal glycaemia was 47.3%(n=18).20 patients (26.7%) were associated with pancreatitis, including 15 patients (75.0%) with acute pancreatitis, 1 patient (5.0%) with recurrent pancreatitis, and 4 patients (20.0%) with chronic pancreatitis. Thirty-three patients ( 36.2%) suffered other congenital organ malformations, including 21 patients (63.6%) with splenic malformation, 8 patients (24.2%) with heart malformation, and 17 patients (51.5%) with multi-organs malformations like gastrointestinal malformation, azygos vein and inferior cava vena fusion, duodenal and biliary atresia and renal absence.Conclusions The main diagnostic criteria of DPA was the absence of dorsal pancreatic duct.Diabetes was the most common complication followed by pancreatitis.

Case-based teaching (CBT) on the basis of treatment guidelines was carried out to develop standard medical behavior, improve learning efficiency and students' ability of solving clini-cal problems. In clinical internship teaching, guidelines for common and frequently-occurring respira-tory diseases and CBT were organically combined. Cases were carefully selected and questions were meticulously set. Guidelines were thoroughly analyzed and teaching was reasonably evaluated. There-fore, students' learning interests were initiated and learning efficiency was improved. It not only trained evidence-based medicine thinking of intern students, but also improved the teaching ability of clinical teachers.