Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Functional gastrointestinal disease(FGID)and inflammatory bowel disease(IBD)are two common gastrointestinal diseases in clinical practice.FGID refers to non-structural changes in gastrointestinal function,with irritable bowel syndrome(IBS)and functional dyspepsia(FD)being the common types.On the other hand,IBD is a group of chronic inflammatory bowel diseases with well-defined pathological features,mainly including Crohn's disease(CD)and ulcerative colitis(UC).Over the past decades,the incidence rates of both FG1D and IBD have increased with years,accompanied by high recurrence rates,and the clinical outcomes remain unsatisfactory,which seriously affect the physical and mental health of patients.Further research has revealed that neuropsychiatric abnormalities,including mental and psychological disorders,play important roles in the occurrence and development of FGID and IBD.The comorbidity of gastrointestinal and psychiatric diseases shares a common pathophysiological basis,that is,the abnormalities in the bidirectional communication between the gut and the central nervous system,and the theory of brain-gut axis has emerged as a research hotspot in this field.Better therapeutic outcomes can be achieved by screening and identifying key brain regions closely related to FGID and IBD through quantifiable assessments,and implementing combined pharmacotherapy on both the digestive system and the nervous system based on the theory of brain-gut axis.Current neuroimaging studies have provided the preliminary results for understanding the changes in the nervous system in FGID and IBD patients,but there is still a lack of systematic evaluation of the application of neuroimaging studies based on the brain-gut axis in gastrointestinal diseases.This paper reviewed the changes in brain structure and function associated with FGID and IBD,and the neuroimaging-based analysis of the brain-gut axis theory in the occurrence and development of these diseases,in order to provide theoretical basis for future personalized precision medicine of FGID and IBD based on the brain-gut axis.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.
Humans ; Colorectal Neoplasms/therapy* ; Machine Learning ; Female ; Male ; Middle Aged ; Neoplasm Metastasis ; Algorithms ; Medicine, Chinese Traditional/methods* ; Aged ; Adult ; Kaplan-Meier Estimate

Objective: To analyze the trend of physical fitness of freshmen of Fujian Medical University from 2014 to 2022, so as to provide theoretical basis and reference for deepening the reform of physical education in medical colleges. Methods: Based on the physical examination and health monitoring data of 23 874 freshmen from Fujian Medical University during 2014 to 2022, Pearson correlation analysis and linear regression analysis were used to analyze the development trend of physical health of freshmen over the past 9 years. Results: From 2014 to 2022, there was an upward trend in height, weight, body mass index (BMI), and lung capacity among firstyear male students, firstyear girls showed an upward trend in height, weight, BMI, lung capacity, standing long jump, sitting forward bending, sit ups, and 800 meter run performance. From the perspective of effect size d and explanatory rate r2, male lung capacity (d=0.60) showed a moderate effect, while the lung capacity (d=0.81) and sit ups (d=1.01) of female students showed a moderate effect,and sitting forward flexion (d=0.57) showed a large effect (P<0.01). Conclusions Physical form level of freshmen have steadily improved during 2014 to 2022. Female students show a more clear increasing trend in standing long jump, sitting forward bending, sit ups, and 800 meter run.

Objective To evaluate the molluscicidal effects and costs of spraying 20% suspension concentrate of pyricloben-zuron sulphate (SCPS) with drones against Pomacea canaliculata in paddy environments, so as to provide insights into the extensive applications of pyriclobenzuron against P. canaliculata. Methods On July 2022, a paddy field was selected from Nanchang City, Jiangxi Province as the study area, and 72 independent rectangular plots measuring 2 m × 1 m were allocated in the study area, with 1 m interval between each plot, and 20 P. canaliculata snails gently placed in each plot. The activity of 25% wettable powder of pyriclobenzuron sulphate (WPPS) by manual spraying at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m² against P. canaliculata was tested in 54 plots, and manual spraying of 50% wettable powder of niclosamide ethanolamine salt (WPNES) at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with 9 plots in each group. The activity of SCPS against P. canaliculata was tested in the remaining 18 plots. Based on the molluscicidal tests of WPPS, the molluscicidal effect of SCPS by manual spraying at doses of 0.20, 0.30, 0.40 g/m² and 0.50 g/m² against P. canaliculata was evaluated, and manual spraying of WPNES at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with three plots in each group. On July 2023, 14 paddy fields with a mean living P. canaliculata density of > 5 snails/m² were selected from Yujiang District, Yingtan City, Jiangxi Province for molluscicidal tests. Based on the molluscicidal effect of pyriclobenzuron against P. canaliculata in plots, the molluscicidal effects of WPPS by manual spraying at doses of 0.25, 0.50 g/m² and 1.00 g/m² and manual applications of WPPS at dose of 0.25, 0.50, 1.00 g/m² and 2.00 g/m² mixed with soil were tested, and manual spraying of 0.10 g/m² WPNES served as a chemical control group, while manual spraying of the same volume of clean water served as a blank control, with one paddy field in each group. Based on the effect of pyriclobenzuron against P. canaliculata in plots, the activity of SCPS sprayed with drones at doses of 0.25 g/m² and 0.50 g/m² mixed in water at 2 kg/667 m² and 4 kg/667 m² was tested against P. canaliculata, and spraying of the same volume of clean water with drones served as a blank control. All P. canaliculata snails were captured 3 days and 7 days following chemical treatment in plots and paddy fields and identified for survival, and the mortality and corrected mortality of P. canaliculata snails were estimated. In addition, the areas of chemical treatment, amount of molluscicide use and labor costs of chemical treatment were estimated in molluscicidal tests in paddy fields, and the costs of chemical treatment for an area covering 667 m² by drones and manual applications were calculated. Results The mortality of P. canaliculata snails was all 100% in plots 3 days and 7 days following spraying WPPS at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m², and the mortality rates of P. canaliculata snails were 66.67% to 100.00% 3 days post-treatment with SCPS at various doses (χ² = 277.897, P < 0.05) and 76.67% to 100.00% 7 days post-treatment (χ² = 274.206, P < 0.05). The mortality rates of P. canaliculata snails were 98.19% to 100.00% 3 days post-treatment with WPPS at various doses in paddy fields. There was a significant difference in the mortality of P. canaliculata snails among WPPS treatment groups and controls (χ² = 270.778, P < 0.05), and there were no significant differences between WPPS treatment groups and the chemical control group (all P values > 0.05), while there were significant differences in the mortality of P. canaliculata snails between WPPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 89.83% to 95.31% 3 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 132.892, P < 0.05). There were no significant differences in the mortality of P. canaliculata snails among SCPS treatment groups or water mixture groups (all P values > 0.05), and there were significant differences in the mortality of P. canaliculata snails between SCPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 94.62% to 100.00% 7 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 266.932, P < 0.05), with the highest mortality found following spraying 0.50 g/m² SCPS mixed in 2 kg/667 m² water with drones (P < 0.05). The costs of P. canaliculata snail control by drones and manually were 35.85 Yuan/667 m² and 43.33 Yuan/667 m²; however, the snail control efficiency was 6.67 times higher by drones than by manual applications. Conclusions SCPS sprayed with drones is highly active against P. canaliculata snails in paddy fields. SCPS sprayed with drones is highly efficient and low in cost for P. canaliculata snail control in paddy fields, beaches and river courses.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.