AIM:To elucidate the mechanism by which Polygonatum sibiricum polysaccharides(PSP)miti-gate high-sugar diet-induced neuroinflammation through the gut microbiota-serum metabolome axis.METHODS:Fifty male ICR mice were divided into 5 groups:control group,model group,low-dose(250 mg/kg)PSP group,high-dose(500 mg/kg)PSP group,and donepezil hydrochloride(3 mg/kg)group.The neuroinflammation model was established through administration of high-sugar chow and 10%sucrose water for 12 weeks.Cognitive function assessment was per-formed utilizing the Morris water maze.Hippocampal histopathology was examined by hematoxylin-eosin(HE)staining,activated microglia were assessed via immunofluorescence,and neuronal apoptosis was evaluated by TUNEL assay.Serum and hippocampal levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)were quantified using ELISA and Western blot.Gut microbiota diversity and serum untargeted metabolomics analyses were car-ried out employing 16S rRNA sequencing and LC-MS/GC-MS,respectively.Differential metabolites were screened,and key metabolic pathways were enriched using MetaboAnalyst 6.0.Spearman correlation analysis established relationships between gut microbiota,metabolites,and inflammatory factors.RESULTS:Model mice demonstrated increased escape latency(P<0.05 or P<0.01)and decreased platform crossings(P<0.01)compared with controls,which were reversed by PSP treatment(P<0.05 or P<0.01).Treatment with PSP substantially reduced IL-6,IL-1β,TNF-α and NO levels in se-rum and hippocampus(P<0.05 or P<0.01),diminished inflammatory infiltration,inhibited microglial activation,and re-duced neuronal damage.Gut microbiota analysis demonstrated that PSP increased Lactobacillus and Bacteroides abun-dance while reducing Alistipes(P<0.05).Metabolomics identified 15 differential metabolites(including betaine,kyotor-phin and ε-caprolactam)and highlighted the significance of alanine,aspartate and glutamate metabolism pathways.Spear-man analysis revealed that abundance of Alistipes and Bacteroides were positively correlated with IL-1β(P<0.05),while abundance of Lactobacillus was negatively correlated with inflammatory factors(P<0.05 or P<0.01).Key metabolites(be-taine,kyotorphin,ε-caprolactam,trans-cinnamate,cis-zeatin and galactitol)showed strong associations with inflamma-tion factors(P<0.05 or P<0.01).CONCLUSION:Treatment with PSP attenuates neuroinflammation through modula-tion of gut microbiota(Lactobacillus,Bacteroides and Alistipes),regulation of metabolites(betaine,kyotorphin and so on),and targeting amino acid metabolism pathways.

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.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

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 current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

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 evaluate the effects of normally positioned flap(NPF)and coronally advanced flap(CAF)techniques on clinical results after epulis excision.Methods·A total of 55 patients with epulis who visited the Department of Periodontology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from August 2022 to December 2023 were included.The patients were divided into the NPF group and the CAF group.After epulis excision,the surgical area was closed using NPF or CAF technique.The following parameters were recorded:baseline epulis width(EW)and epulis height(EH);papilla width(PW)and papilla height(PH)at 6 months post-surgery;probing depth(PD),attachment loss(AL),and keratinized gingiva width(KGW)at both baseline and 6 months post-surgery.The esthetic outcomes were evaluated using a visual analog scale(VAS)by 2 periodontal specialists.t test was used to compare the differences in periodontal indices between baseline and 6 months post-surgery,as well as between the 2 flap techniques.Results·At 6 months post-surgery,PD of the CAF group was(1.68±0.79)mm,significantly lower than at baseline(P<0.001),but not significantly different from that in the NPF group(P=0.365);the AL in the CAF group was(1.26±1.18)mm,not significantly different from baseline(P=0.746),but significantly lower than in the NPF group(P<0.001).At 6 months post-surgery,PH of the CAF group was(3.74±0.62)mm,significantly higher than that in the NPF group(P<0.001),and the VAS score of the CAF group was significantly higher than that of the NPF group(P<0.001).Conclusion·Compared with NPF,CAF could effectively improve post-surgical KGW and reduce AL,which could prevent periodontal soft tissue defects,and improve esthetic outcome after epulis excision.

Objective·To evaluate the effects of normally positioned flap(NPF)and coronally advanced flap(CAF)techniques on clinical results after epulis excision.Methods·A total of 55 patients with epulis who visited the Department of Periodontology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from August 2022 to December 2023 were included.The patients were divided into the NPF group and the CAF group.After epulis excision,the surgical area was closed using NPF or CAF technique.The following parameters were recorded:baseline epulis width(EW)and epulis height(EH);papilla width(PW)and papilla height(PH)at 6 months post-surgery;probing depth(PD),attachment loss(AL),and keratinized gingiva width(KGW)at both baseline and 6 months post-surgery.The esthetic outcomes were evaluated using a visual analog scale(VAS)by 2 periodontal specialists.t test was used to compare the differences in periodontal indices between baseline and 6 months post-surgery,as well as between the 2 flap techniques.Results·At 6 months post-surgery,PD of the CAF group was(1.68±0.79)mm,significantly lower than at baseline(P<0.001),but not significantly different from that in the NPF group(P=0.365);the AL in the CAF group was(1.26±1.18)mm,not significantly different from baseline(P=0.746),but significantly lower than in the NPF group(P<0.001).At 6 months post-surgery,PH of the CAF group was(3.74±0.62)mm,significantly higher than that in the NPF group(P<0.001),and the VAS score of the CAF group was significantly higher than that of the NPF group(P<0.001).Conclusion·Compared with NPF,CAF could effectively improve post-surgical KGW and reduce AL,which could prevent periodontal soft tissue defects,and improve esthetic outcome after epulis excision.

AIM:To elucidate the mechanism by which Polygonatum sibiricum polysaccharides(PSP)miti-gate high-sugar diet-induced neuroinflammation through the gut microbiota-serum metabolome axis.METHODS:Fifty male ICR mice were divided into 5 groups:control group,model group,low-dose(250 mg/kg)PSP group,high-dose(500 mg/kg)PSP group,and donepezil hydrochloride(3 mg/kg)group.The neuroinflammation model was established through administration of high-sugar chow and 10%sucrose water for 12 weeks.Cognitive function assessment was per-formed utilizing the Morris water maze.Hippocampal histopathology was examined by hematoxylin-eosin(HE)staining,activated microglia were assessed via immunofluorescence,and neuronal apoptosis was evaluated by TUNEL assay.Serum and hippocampal levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)were quantified using ELISA and Western blot.Gut microbiota diversity and serum untargeted metabolomics analyses were car-ried out employing 16S rRNA sequencing and LC-MS/GC-MS,respectively.Differential metabolites were screened,and key metabolic pathways were enriched using MetaboAnalyst 6.0.Spearman correlation analysis established relationships between gut microbiota,metabolites,and inflammatory factors.RESULTS:Model mice demonstrated increased escape latency(P<0.05 or P<0.01)and decreased platform crossings(P<0.01)compared with controls,which were reversed by PSP treatment(P<0.05 or P<0.01).Treatment with PSP substantially reduced IL-6,IL-1β,TNF-α and NO levels in se-rum and hippocampus(P<0.05 or P<0.01),diminished inflammatory infiltration,inhibited microglial activation,and re-duced neuronal damage.Gut microbiota analysis demonstrated that PSP increased Lactobacillus and Bacteroides abun-dance while reducing Alistipes(P<0.05).Metabolomics identified 15 differential metabolites(including betaine,kyotor-phin and ε-caprolactam)and highlighted the significance of alanine,aspartate and glutamate metabolism pathways.Spear-man analysis revealed that abundance of Alistipes and Bacteroides were positively correlated with IL-1β(P<0.05),while abundance of Lactobacillus was negatively correlated with inflammatory factors(P<0.05 or P<0.01).Key metabolites(be-taine,kyotorphin,ε-caprolactam,trans-cinnamate,cis-zeatin and galactitol)showed strong associations with inflamma-tion factors(P<0.05 or P<0.01).CONCLUSION:Treatment with PSP attenuates neuroinflammation through modula-tion of gut microbiota(Lactobacillus,Bacteroides and Alistipes),regulation of metabolites(betaine,kyotorphin and so on),and targeting amino acid metabolism pathways.