Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Graduate education is critical for cultivation of high-level talents and promotion of technological innovation. Strengthening the management of graduate education is of great practical significance for ensuring and improving the quality of graduate education. The expansion of graduate education brings challenges to educational resources and management models, requiring research institutions to ensure educational quality and adapt to social needs. Based on the particularity of research institutes, this article takes the practice of radiation health graduate education as an example to explore the graduate student management elements of form teachers in research institutes. Our research provides a reference for improving the management level of graduate students in research institutes. Graduate form teachers are organizers, implementers, and mentors of graduate ideological education, academic culture, daily management, employment and entrepreneurship, and mental health education. They play an important role as a bridge and link in graduate education and cultivation. Faced with the challenges of graduate education in the new era, form teachers should continuously explore work methods that adapt to the needs of the era. They should also focus on reinforcing ideological and political theories, improving professional skills, establishing and improving management systems, and leveraging the role of student cadres to ensure the high-quality development of graduate education in research institutes.

Background::Liver cancer remains the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, causing a heavy burden globally. An updated assessment of the global epidemiology of the liver cancer burden that addresses geographical disparities is necessary to better understand and promote healthcare delivery.Methods::Data were extracted from the GLOBOCAN 2022 database, including the number, crude, and age-standardized rates of incidence and mortality at the global, country, continent, and human development index (HDI) regional levels. Age-standardized rates (incidence and mortality) per 100,000 person-years were adjusted based on the Segi-Doll World standard population. The mortality-to-incidence ratios (MIR) for each region and country were calculated. The HDI and gross national income (GNI) for 2022 were obtained, and a Pearson correlation analysis was conducted with the incidence, mortality, and MIR.Results::In 2022, approximately 866,136 new liver cancer cases and 758,725 related deaths were recorded worldwide, with a global MIR of 0.86. Males had a disproportionately higher burden than females across all levels, and the highest burden was observed in the elderly population. Geographically, the regions with the highest incidence rates included Micronesia, Eastern Asia, and Northern Africa, and the regions with the highest mortality rates included Northern Africa, Southeastern Asia, Eastern Asia, and Micronesia. Notably, Mongolia had a strikingly high burden compared to other countries. The highest MIR was observed in North America and the lowest in Africa. Negative associations of HDI and GNI with liver cancer mortality and MIR were identified, irrespective of sex.Conclusions::The current liver cancer burden underscores the presence of remarkable geographic heterogeneity, which is particularly evident across countries with varying HDI levels, highlighting the urgent need to prioritize health accessibility and availability to achieve health inequities.

Objective To investigate the pharmacological effects of"Yajieshaba"on mice with alcohol-induced liver injury and to investigate the mechanism of the impact of"Yajieshaba"on the regulation of intestinal flora by 16S rDNA technology.Methods Healthy male KM mice were randomly divided into control,model,"Yajieshaba"low,medium,and high dose(0.39,1.17 and 3.51 g·kg-1)groups and Bifendatatum(2.93 mg·kg-1)groups,with eight mice in each group.After one week of pre-administration of"Yajieshaba",a mouse model of acute alcoholic liver injury was established by a single instillation of 56%alcohol,and the levels of AST and ALT in the serum of mice were measured,and the morphological changes of liver histology were observed by HE staining;secondly,faecal DNA was extracted from each group under aseptic operation,and 16S rDNA sequencing and differential analysis by alpha diversity and species composition at the phylum and genus levels were performed.Results The results showed that the biochemical indexes of liver function(ALT and AST)were significantly improved by"Yajieshaba",and the degree of liver damage was significantly reduced by HE staining.At the phylum level,it significantly decreased the abundance of Aspergillus and increased the quantity of Bacteroides;at the genus level,it significantly up-regulated the plenty of Bacteroides and Prevotella and downregulated a lot of Prevotella and Helicobacter.At the genus level,"Yajieshaba"significantly up-regulated the abundance of Bacillus spp.and Prevotella spp.and down-regulated the abundance of Prevotella spp.and Helicobacter spp.Conclusion"Yajieshaba"may play an anti-acute alcoholic liver injury effect by regulating the intestinal flora and metabolites.

Objective     To explore the causes of conversion to thoracotomy in patients with minimally invasive esophagectomy (MIE) in a surgical team, and to obtain a deeper understanding of the timing of conversion in MIE. Methods     The clinical data of patients who underwent MIE between September 9, 2011 and February 12, 2022 by a single surgical team in the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. The main influencing factors and perioperative mortality of patients who converted to thoracotomy in this group were analyzed. Results     In the cohort of 791 consecutive patients with MIE, there were 520 males and 271 females, including 29 patients of multiple esophageal cancer, 156 patients of upper thoracic cancer, 524 patients of middle thoracic cancer, and 82 patients of lower thoracic cancer. And 46 patients were converted to thoracotomy for different causes. The main causes for thoracotomy were advanced stage tumor (26 patients), anesthesia-related factors (5 patients), extensive thoracic adhesions (6 patients), and accidental injury of important structures (8 patients). There was a statistical difference in the distribution of tumor locations between patients who converted to thoracotomy and the MIE patients (P<0.05). The proportion of multiple and upper thoracic cancer in patients who converted to thoracotomy was higher than that in the MIE patients, while the proportion of lower thoracic cancer was lower than that in the MIE patients. The perioperative mortality of the thoracotomy patients was not significantly different from that of the MIE patients (P=1.000). Conclusion     In MIE, advanced-stage tumor, anesthesia-related factors,extensive thoracic adhesions, and accidental injury of important structures are the main causes of conversion to thoracotomy. The rate varies at different tumor locations. Intraoperative conversion to thoracotomy does not affect the perioperative mortality of MIE.

Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell/pathology* ; Precancerous Conditions/pathology* ; Early Diagnosis

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms