Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective To explore the probability and associated factors of pulmonary fibrosis in 350 cases of elderly pneumonia. Methods Elderly patients who received diagnosis and treatment at Changzhi Medical College Affiliated Peace Hospital from January 2018 to December 2022 were selected, and 350 patients who met the criteria were included in the study. Analyze its clinical data, incidence of pulmonary fibrosis, and analyze the relationship between the two. Results The average age of 350 patients was (63.51 ± 5.74) years old; 219 cases were common type , 72 cases were severe type, and 59 cases were critically ill. At admission, the CT signs were: ground glass in 66 cases (18.86%) , paving stone in 37 cases (10.57%), consolidation in 73 cases (20.86%), nodules in 93 cases (26.57%) , fried egg sign in 20 cases (5.71%) , and mosaic sign in 61 cases (17.43%). At discharge, the lesion signs were as follows: 61 cases (17.43%) had no lesions, 207 cases (59.14%) maintained the original lesion signs, and 82 cases (23.43%) evolved into other signs. 76 cases of pulmonary fibrosis were discharged, with an incidence rate of 21.71%. There were significant differences in the incidence of pulmonary fibrosis among patients with different ages, lesion evolution during treatment, lesion signs at discharge, and clinical stages (all P<0.001). Pulmonary fibrosis is positively correlated with age (P=0.047), lesion signs at discharge (P=0.032), and clinical classification (P=0.010). The incidence of lesions presenting as paving stones (P=0.014) and fibrosis in critically ill patients (P=0.013) at discharge is higher. Age increase (P=0.047) , wide range of lesions at admission (P=0.042), evolution of lesions into other signs at discharge (P=0.016), and clinical classification as severe (P=0.008) or critically ill (P=0.021) are independent risk factors for the development of pulmonary fibrosis in elderly pneumonia patients. Conclusion The incidence of pulmonary fibrosis in elderly patients exceeds 20%. Increasing age, wide range of lesions upon admission, evolution of lesions into other signs upon discharge, and clinical classification as severe or critically ill are independent risk factors for the occurrence of pulmonary fibrosis in elderly pneumonia patients.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

italic>Sophora flavescens is a traditional Chinese medicine rich in flavonoids and has wide application potential in drug development and clinical practice. In this study, a total of 227 flavonoids were detected among five tissues of S. flavescens during anthesis using widely targeted metabolomics techniques. There were 137 flavonoids shared by five S. flavescens tissues and 18 root-specific flavonoids. There were 156, 155, 156 and 150 differentially accumulated metabolites identified in stem, leaf, flower, and young pod, respectively, compared with root. Forty-seven potentially active flavonoid components in S. flavescens were identified using the PubChem and SwissADME databases. The 58 potential target proteins for these potentially active components were predicted to be important in the treatment of type 2 diabetes mellitus (T2DM) based on the SwissTargetPrediction and GeneCards database. These 58 target proteins were used to construct a protein-protein interaction network through the STRING database, from which we performed GO and KEGG functional enrichment analysis. The mechanisms by which S. flavescens flavonoids may be useful in the treatment of T2DM was further explored in a multi-level and systematic way based on a "component-target-pathway" network. Finally, ten key potentially effective components were identified and found to be mainly distributed in the roots, flowers, and pods, and their content varied significantly between tissues. The results predict that the key targets of S. flavescens flavonoids in the treatment of T2DM are AKT1, ESR1, EGFR, PIK3R1, TNF and PTGS2, and that they play a hypoglycemic role through the regulation of endocrine resistance, AGE-RAGE, the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance and other signaling pathways. This analysis of the tissue distribution and network pharmacology of S. flavescens flavonoids provides a theoretical basis for further studies on S. flavescens metabolites, the rational development and utilization of the S. flavescens aboveground parts, and initiates a comprehensive exploration of the mechanisms by which S. flavescens can be used in the treatment of T2DM.

Standardized surgical management of postoperative specimens of gastric cancer is an important part of the standardized diagnosis and treatment of gastric cancer. It can reflect the accurate number and detailed distribution of lymph nodes in the specimen and lay the foundation for accurate and standardized pathological reports after surgery. Meanwhile, it can evaluate the scope of intraoperative lymph node dissection, the safety of cutting edge, and the standardization of surgery (principle of en-bloc dissection), which is an important means of surgical quality control. It also provides accurate research samples for further research and is an important way for young surgeons to train their clinical skills. The surgical management of postoperative specimens for gastric cancer needs to be standardized, including specimen processing personnel, processing flow, resection margin examination, lymph node sorting, measurement after specimen dissection, storage of biological specimens, documentation of recorded data, etc. The promotion of standardized surgical management of specimens after radical gastrectomy can promote the homogenization of gastric cancer surgical diagnosis and treatment in medical institutions and further promote the high-quality development of gastric cancer surgery in China.
Gastrectomy ; Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes/surgery* ; Stomach Neoplasms/surgery*

OBJECTIVE: To evaluate the effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring. METHODS: Twenty children with snoring aged 4-6 years of either gender (ASA grade Ⅰ and Ⅱ) were selected for adenoidectomy.Before, during and 3 days after the operation, salivary melatonin levels of the children were measured at 11 selected time points (T1-T11).The illumination intensity and body temperature of the children were recorded at each time point of measurement.The sleep time of the children in 3 days after the operation was recorded, and postoperative pain scores (FLACC) and Riker and Rehabilitation Quality Rating Scale-15(QoR-15) scores were assessed.Sleep Apnea Life Quality Evaluation Questionnaire (OSA-18) was used to evaluate postoperative recovery of the children at 28 days after the operation.The incidence of major adverse events of the children during hospitalization was recorded. RESULTS: No significant difference was found in baseline salivary melatonin level among the 20 children before the operation.Salivary melatonin level at 7 am after the operation (T8) was significantly lowered as compared with that before the surgery (T4)( CONCLUSIONS In preschool children with snoring, general anesthesia affects but does not inhibit melatonin secretion on the first night after surgery, and minor surgeries under general anesthesia in the morning do not cause significant changes in melatonin secretion to cause disturbance of the circadian rhythm in these children.
Anesthesia, General/adverse effects* ; Bodily Secretions ; Child ; Child, Preschool ; Circadian Rhythm ; Humans ; Melatonin ; Snoring

The quality control and standardization of procedures in radical gastrectomy for gastric cancer, especially the standardized processing of specimens after radical gastrectomy for gastric cancer, is very important. It is not only the basis of accurate pathological staging, but also the evidence of surgical quality and the original data of clinical research, which plays a pivotal role. The examination and classification of lymph nodes, specimens processing records, and data uploading and archiving after radical gastrectomy for gastric cancer are indispensable. It is necessary for surgeons to participate in the processing of surgical specimens. This article will combine the current research status and progress at home and abroad to review the standardized processing of specimens after radical gastrectomy for gastric cancer.
Gastrectomy ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Neoplasm Staging ; Stomach Neoplasms/surgery*

Objective: Traditional Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy can greatly decrease the anastomosis-related complications and reduce the incidence of reflux esophagitis, but its complexity limits the wide application. To decrease the complexity of Kamikawa anastomosis, the surgical team of Changzhi People's Hospital of Shanxi Changzhi Medical College improved this technique by using novel notion and reduced surgical procedures. This study aims to evaluate the efficacy and safety of modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy. Methods: A descriptive cohort study was carried out. Case enrollment criteria: (1) upper gastric carcinoma or esophagogastric junction carcinoma without distant metastasis was confirmed by preoperative gastroscopic biopsy and imaging examination; (2) tumor diameter was less than 4 cm; (3) preoperative clinical staging was cT1-3N1M0. Exclusion criteria: (1) patients received preoperative neoadjuvant chemotherapy; (2) patients had severe heart or lung disease, or poor nutritional status so that they could not tolerate surgery. Clinical data of 25 patients with upper gastric carcinoma or esophagogastric junction carcinoma who underwent modified Kamikawa anastomosis in digestive tract reconstruction in Heji Hospital (8 cases) and Changzhi People's Hospital (17 cases) from April 2019 to December 2020 were retrospectively collected. Of 25 patients, 21 were male and 4 were female, with mean age of 63.0 (49 to 78) years; 3 underwent open surgery and 22 underwent laparoscopic surgery. The modified Kamikawa anastomosis was as follows: (1) the novel notion of total mesangial resection of the esophagogastric junction was applied to facilitate the thorough removal of lymph nodes and facilitate hand-sewn anastomosis and embedding; (2) the diameter of the anastomotic stoma was selected according to the diameter of the esophageal stump, between 2.5 and 3.5 cm, to reduce the occurrence of anastomotic stenosis; (3) an ultrasonic scalpel was used to incise the esophageal stump, which could not only prevent bleeding of the esophageal stump, but also closely seal the esophageal mucosa, muscle layer and serosa to prevent esophageal mucosa retraction; (4) barbed suture was used to suture the remnant stomach fundus and esophagus to fix the stomach fundus in order to reduce the cumbersome and difficult intermittent sutures in a small space; (5) two barbed sutures were used to continuously suture the front and back walls of the anastomosis and complete the suture and fixation of the muscle flap. Relevant indicators of surgical safety, postoperative complications (using the Clavien-Dindo classification), esophageal reflux symptoms and the occurrence of esophagitis (using Los Angeles classification) were analyzed. The gastroesophageal reflux disease (GERD) score, gastroscopy, multi-position digestive tract radiography during postoperative follow-up were used to evaluate the residual gastric motility and anti-reflux efficacy. Results: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy was successfully performed in 25 patients. The surgical time was (5.8±1.8) hours, the intraoperative blood loss was (89.2±11.8) ml, and the average hospital stay was (13.8±2.9) days. Three cases (12.0%) developed postoperative anastomotic stenosis as Clavien-Dindo grade III and were healed after endoscopic dilation treatment. Postoperative upper gastrointestinal radiography showed 1 case (4.0%) with reflux symptoms as Clavien-Dindo grade I. Gastroscopy showed no signs of reflux esophagitis, and its Los Angeles classification was A grade. No anastomotic bleeding, local infection and death were found in all the patients. At postoperative 6-month of follow-up, GERD score showed no significant difference compared to pre-operation (2.7±0.6 vs. 2.4±1.0, t=-1.495, P=0.148). Conclusion: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy is safe and feasible with good anti-reflux efficacy.
Aged ; Anastomosis, Surgical ; Cohort Studies ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Retrospective Studies

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome