Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.

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 investigate the change trend in the burden of 5 common malignant tumors of digestive system (esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer) in the Chinese population from 1990 to 2021.Methods:The descriptive epidemio-logic method was conducted. The number of new cases, crude incidence rate, age-standardized incidence rate, the number of deaths, crude mortality rate and age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021 of the Global Burden of Disease were collected. The age-standardized rate was calculated based on the standardized demographics of the whole world in the Global Burden of Disease for the year 2021. Observation indicators: (1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (2) the mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (3) the change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021; (4) the change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The Joinpoint regression model was constructed for trend analysis, specifically to calculate the annual percentage change, average annual percentage change (AAPC), and their 95% confidence interval ( CI) for age-standardized incidence and mortality rates for each cancer type at different time periods. Results:(1) The incidence of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of new cases of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 207 495, 407 471, 158 389, 37 818 and 96 434 in 1990 to 320 805, 611 799, 658 321, 118 665 and 196 637 in 2021. The crude incidence rates of the above cancer types changed from 17.64/100 000, 34.64/100 000, 13.46/100 000, 3.21/100 000, 8.20/100 000 in 1990 to 22.55/100 000, 43.00/100 000, 46.27/100 000, 8.34/100 000, 13.82/100 000 in 2021. The new cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increasing trend, with absolute changes of 54.61%, 50.15%, 315.64%, 213.78%, and 103.91%, respectively. (2) The mortality of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The number of deaths of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer in the Chinese population changed from 210 821, 374 066, 119 303, 38 883 and 94 937 in 1990 to 296 443, 445 013, 275 129, 119 602 and 172 068 in 2021. The crude death rates of the above cancer types changed from 17.92/100 000, 31.80/100 000, 10.14/100 000, 3.31/100 000, 8.07/100 000 in 1990 to 20.84/100 000, 31.28/100 000, 19.34/100 000, 8.41/100 000, 12.09/100 000 in 2021. Death cases of esophageal cancer, stomach cancer, colorectal cancer, pancreatic cancer, and liver cancer all showed an increa-sing trend, with absolute changes of 40.61%, 18.97%, 130.61%,207.59%, and 81.24%, respectively. (3) The change trend of age-standardized incidence rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trends of age-standardized incidence rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 5 periods, respectively, and the AAPCs of age-standardized incidence rates of the above cancer types were -1.60% (95% CI as -1.78% to -1.42%), -1.60% (95% CI as -1.78% to -1.43%), 1.66% (95% CI as 1.39% to 1.94%), 0.72% (95% CI as 0.36% to 1.08%), and -0.31% (95% CI as -0.39% to -0.23%). (4) The change trend of age-standardized mortality rate of 5 common malignant tumors of digestive system in the Chinese population from 1990 to 2021. The change trend of age-standardized mortality rates of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, and liver cancer in the Chinese population were divided into 5, 5, 4, 5, and 4 periods, respectively, and the AAPC of age-standardized mortality rates for each of the above mentioned cancer types were -1.96% (95% CI as -2.03% to -1.90%), -2.44% (95% CI as -2.50% to -2.38%), -0.49% (95% CI as -0.58% to -0.41%), 0.56% (95% CI as 0.48% to 0.63%), and -0.68% (95% CI as -0.89% to -0.52%). Conclusions:From 1990 to 2021, the disease burden of esophageal cancer, gastric cancer and liver cancer in the Chinese population show a downward trend. The standardized incidence of colorectal cancer shows an upward trend, and the standardized mortality rate shows a downward trend. The disease burden of pancreatic cancer shows an upward trend.

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 investigate the effects of Xingnao Yisui Decoction on the behaviour of vascular dementia (VaD) rats and the apoptosis of neurons in the CA1 region of the hippocampus; To explore its mechanism of action.Methods:Totally 60 adult SD rats with similar levels of cognitive function were selected and divided into Xingnao Yisui Decoction high-, medium- and low-dosage groups, donepezil group, model group and sham-operation group according to the random number table method, with 10 rats in each group. Except for the sham-operation group, the VaD model was prepared using a modified bilateral common carotid artery ligation method in all the groups. Xingnao Yisui Decoction high-, medium- and low-dosage groups were gavaged with 19.62, 9.81, 4.91 g/(kg·d) of Xingnao Yisui Decoction respectively, the donepezil group was gavaged with 0.5 mg/(kg·d) of donepezil solution, and the sham-operation group and the model group were given equal amount of saline gavage, 1 time/d for 4 weeks. Morris water maze experiment was used to observe the behavioral changes in each group, TUNEL staining was used to observe the apoptosis of neurons in CA1 area of hippocampus. Realtime PCR was used to detect the mRNA expression of NF-κB and MMP-9. ELISA was used to detect the changes of serum NF-κB, MMP-9, p53, Bcl-2 and Bax protein levels.Results:Compared with the model group, the escape latency of rats in the donepezil group and Xingnao Yisui Decoction high-, medium- and low-dosage groups was shortened ( P<0.05); the times of crossing the platform and the stay time in the target quadrant increased ( P<0.05); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the mRNA expression of NF- κB and MMP-9 in hippocampal mRNA level decreased ( P<0.01); the content of NF-κB, MMP-9, p53 and Bax decreased ( P<0.01), while the content of Bcl-2 increased ( P<0.01). Conclusion:Xingnao Yisui Decoction can effectively mediate the NF-κB-MMP-9 pathway to improve the permeability of the blood-brain barrier and regulate p53-Bcl-2-Bax to reduce apoptosis of neurons in CA1 area of hippocampus, thus significantly improve the learning and memory ability of VaD rats.

Objective Performing physical tasks in the low-pressure environment of space poses a significant physiological challenge for astronauts.This study investigates the localized thermophysiological effects of typical physical tasks on different body segments and analyzes the mechanisms by which low-pressure environments influence human task performance.The findings aim to provide a theoretical basis for the thermal control design of spacesuits,focusing on both localized thermoregulation and overall task performance.Methods Two typical physical tasks—15 kg weighted walking and 25 kg load-carrying—were conducted in a simulated low-pressure composite environment chamber.The chamber was set to an altitude-equivalent pressure of 57 kPa(4500 m),with a temperature of 26℃and humidity of 40％.Six non-acclimatized adult male participants were recruited.After environmental stabilization,12-point skin temperatures were recorded throughout the tasks,and localized temperature data were statistically analyzed.Results Under low-pressure conditions,different body regions exhibited distinct thermal responses over time depending on the task type,while the same body region showed varied responses under different task conditions.During walking,temperatures in the primary active regions(thighs and calves)decreased,with most other body regions(except the pelvis and feet)gradually cooling as the task progressed.In contrast,during load-carrying,temperatures in the primary active regions(back and upper arm muscles)increased significantly.Conclusion Astronauts performing different tasks in low-pressure environments experience distinct localized thermophysiological effects.Therefore,spacesuit thermal control systems should not only account for task intensity and metabolic differences but also adapt localized heating/cooling based on task-specific thermal profiles.This approach enables targeted intelligent thermal regulation,enhancing operational support in specific mission scenarios.

Objective:To analyze the changes in the phylogenetic and antigenic characteristics of the hemagglutinin (HA) gene of influenza virus A(H3N2) [A(H3N2)] during the 2022-2024 influenza seasons in Beijing.Methods:The data of influenza-like cases and A(H3N2) strains from 17 network laboratories and their corresponding sentinel hospitals were collected during the 2022-2024 influenza seasons. The HA genes were amplified and sequenced after extracting nucleic acids of the chosen virus strains. BioEdit, the nucleotide and amino acid sequence identity were conducted, and the maximum likelihood method in MEGA 5.0 software was used to construct the phylogenetic tree of HA genes. Web Logo displayed the amino acid mutation, and the N-glycosylation sites of HA online were analyzed using the NetNGlyc1.0 Server online. The Datamonkey platform was utilized to analyze the positive selection pressure sites of the HA protein.Results:The 2022-2024 influenza season includes 2022-2023 and 2023-2024. During the influenza seasons of 2022-2024, the positive rates of A(H3N2) nucleic acid were 10.35% (2 127/20 543) and 10.47% (4 386/41 876), respectively. In the 2022-2023 influenza season, there were two peaks in the A(H3N2). The comparison of HA genes between all A(H3N2) strains studied with the 2022-2024 vaccine strain (A/Darwin/9/2021) revealed that all of the strains studied have the two amino acid mutations involving 186 and 225 receptor binding sites. There were 31 amino acid substitutions in the 2022-2023 influenza season, of which 18 variant sites involved antigenic determinants. There were 35 amino acid mutations during the 2023-2024 influenza season, of which 14 were related to antigenic determinants. There were changes in the genetic evolutionary subclades of A(H3N2) strains in two influenza seasons: from 2022 to 2023, three evolutionary subclades were co-prevalent together, with the 3C.2a1b.2a.2a.3a.1 accounting for 76.67% (23/30), the 3C.2a1b.2a.1a accounting for 20.00% (6/30), the 3C.2a1b.2a.2a.1 accounting for 3.33% (1/30); from 2023 to 2024, two subclades were prevalent, with 3C.2a1b.2a.2a.3a.1 accounting for 95.12% (39/41) and 3C.2a1b.2a.2a.1 accounting for 4.88% (2/41). The glycosylation site changes of the HA protein of A(H3N2) have been enhanced from 2023 to 2024. The 145 amino acid position of the HA protein of the A(H3N2) was the positive selection site for stress selection site analysis.Conclusions:The evolutionary subclades of the HA gene of A(H3N2) in Beijing showed changes from 2022 to 2024, and the glycosylation site polymorphism of the HA protein of A(H3N2) significantly increased from 2023 to 2024. Continuous monitoring of HA mutations in the A(H3N2) is crucial, providing a basis for developing influenza prevention and control strategies, as well as new strategic support for screening influenza vaccine components, vaccine design, and discovery of drug targets.

Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.