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.

BACKGROUND:Adult stem cell therapy is one of the research hotspots in the field of peripheral nerve injury repair and regeneration.With excellent properties of mesenchymal stem cells such as high acquisition rate,wide source,and rapid proliferation,mesoderm have been regarded as the ideal source of adult stem cells,while ectoderm-derived adult stem cells,especially neural crest stem cells,have certain neurogenic properties and attract more and more attention from researchers. OBJECTIVE:To mainly review the role and mechanism of multifunctional adult stem cells from ectoderm and mesoderm in peripheral nerve injury repair and regeneration,so as to explore the research progress and application prospect of adult stem cells from different sources and discuss the potential application value of adult stem cell therapy and the problems to be solved in connection with clinical studies. METHODS:The first author searched the relevant articles published from December 2001 to February 2024 in PubMed and SinoMed by computer in February 2024.The Chinese and English search terms were"ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration."Finally,69 articles were included and analyzed. RESULTS AND CONCLUSION:(1)Ectodermal adult stem cells have excellent differentiation and regeneration potential,especially epidermal neural crest stems cells,olfactory stem cells,and dental ectomesenchymal stem cells,which have certain neurogenic properties and can express neural specific markers in vitro.However,relevant clinical research needs to be accumulated.(2)There are many types of adult stem cells derived from mesoderm,which are easy to obtain and purify.Among them,the efficacy and safety of bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells in the repair of peripheral nerve injury are supported by clinical trials;that is,they can improve sensory and motor nerve conduction and there are no complications and obvious adverse reactions in follow-up.The acquisition of bone marrow mesenchymal stem cells needs invasive surgery and requires the patient to match the donor bone marrow type,which limit the application to some extent.Although umbilical cord mesenchymal stem cells do not require invasive harvesting,their isolation is difficult and phenotypically unstable.(3)Adult stem cells derived from endoderm often fail to grow in vitro,so the possibility of clinical application is low.(4)In conclusion,bone marrow mesenchymal stem cells are still the first choice for adult stem cell therapy in the treatment of peripheral nerve injury,which is suitable for cases without surgical contraindications and meeting the matching requirements,followed by umbilical cord mesenchymal stem cells supplemented by improved isolation methods and advanced phenotypic stability strategies.(5)Dental ectomesenchymal stem cells and adipose-derived mesenchymal stem cells have high application potential and need to be further tested in clinical trials.Other adult stem cells derived from ectodermal and mesodermal layers have significant advantages in animal and cell experimental studies due to their excellent properties.

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.

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: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 inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Systemic sclerosis（SSc）is a chronic autoimmune disease，and cardiac related complication is one of the leading causes of death of systemic sclerosis patients. Nevertheless，by the time cardiac complications become clinically evident，irreversible myocardial damage has usually already occurred. As a novel echocardiographic technique for assessing myocardial function，speckle-tracking technology can be used for the early identification of subclinical cardiac dysfuction in patients with systemic sclerosis，playing a vital role in the early clinical treatment intervention and prognostic evaluation. This article reviewed the current research status and the latest progress of speckle-tracking technology in cardiac damage in patients with systemic sclerosis.

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.

Objective:To explore the prognostic differences and influencing factors between pancreatic cancer originated from intraductal papillary mucinous neoplasm (IPMN)-termed IC-Ds-and pancreatic cancer concomitant with IPMN (C-PDACs).Methods:Clinical data of 382 patients with pathologically confirmed IPMN who underwent surgical resection in the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Naval Medical University from January 2016 to January 2022 were collected. According to pathological diagnosis, patients were divided into the IC-Ds group ( n=288) and the C-PDACs group ( n=94). The IC-Ds group was further divided into the colloid carcinoma subgroup and the ductal adenocarcinoma subgroup based on pathological typing. Data including age, gender, preoperative CA19-9 level, surgical margin status, lymph node metastasis, pathological grade, T stage, postoperative adjuvant chemotherapy, and survival follow-up were recorded. The median follow-up time was 35.00 months for IC-Ds patients and 29.00 months for C-PDACs patients. Clinicopathological characteristics and prognostic factors were compared between the IC-Ds and C-PDACs groups, as well as between the colloid carcinoma and ductal adenocarcinoma subgroups. Kaplan-Meier curves for overall survival were generated. Results:There were no significant differences in age, gender, R1 resection margin between the IC-Ds group and the C-PDACs group. However, in the C-PDACs group, 70 cases (74.47%) had elevated preoperative CA19-9, 40 cases (42.55%) had lymph node metastasis, 25 cases (26.60%) were pathologically confirmed as poorly differentiated carcinoma after surgery, and 54 cases (57.45%) received postoperative adjuvant chemotherapy; the proportions of all these indicators were higher than those in the IC-Ds group (90/288, 31.25%; 72/288, 25.00%; 32/288, 11.11%; 105/288, 36.46%). In contrast, the proportion of T1 stage in the IC-Ds group was higher (40.97% vs 20.21%), and all these differences were statistically significant (all P value <0.05). Among the 288 patients in the IC-Ds group, 97 cases (33.68%) were colloid carcinoma and 191 cases (66.32%) were ductal adenocarcinoma. There were no significant differences in age, gender, R1 resection margin, proportion of poorly differentiated carcinoma between the two subgroups. However, in the ductal adenocarcinoma subgroup, 67 cases (35.08%) had elevated preoperative CA19-9, 56 cases (29.32%) had lymph node metastasis confirmed by postoperative pathology, and 80 cases (41.88%) received postoperative adjuvant chemotherapy; all these proportions were significantly higher than those in the colloid carcinoma subgroup (23/97, 23.71%; 16/97, 17.02%; 25/97, 26.60%). In addition, the ductal adenocarcinoma subgroup had higher proportions of T2 and T3/T4 stages, while the proportion of T1 stage in the colloid carcinoma subgroup (60/97, 61.86%) was significantly higher than that in the ductal adenocarcinoma subgroup (58/191, 30.37%), with all differences being statistically significant (all P value <0.05). The median survival time was 47.00 months (95% CI 42.91-51.09) in the IC-Ds group and 34.00 months (95% CI 29.67-38.33) in the C-PDACs group. For the IC-Ds subgroups, the median survival time was 59.00 months (95% CI 50.79-67.21) in the colloid carcinoma subgroup and 42.00 months (95% CI 35.15-48.85) in the ductal adenocarcinoma subgroup. Significant differences in median survival time were observed between the IC-Ds and C-PDACs groups, between the colloid carcinoma and ductal adenocarcinoma subgroups, and between the ductal adenocarcinoma subgroup and the C-PDACs group (all P value <0.01). Conclusions:IC-Ds has a better prognosis than C-PDACs, and there is significant heterogeneity within IC-Ds, indicating different biological behaviors between the two types, which requires the development of targeted diagnosis and treatment strategies.

Objective:To explore the prognostic differences and influencing factors between pancreatic cancer originated from intraductal papillary mucinous neoplasm (IPMN)-termed IC-Ds-and pancreatic cancer concomitant with IPMN (C-PDACs).Methods:Clinical data of 382 patients with pathologically confirmed IPMN who underwent surgical resection in the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Naval Medical University from January 2016 to January 2022 were collected. According to pathological diagnosis, patients were divided into the IC-Ds group ( n=288) and the C-PDACs group ( n=94). The IC-Ds group was further divided into the colloid carcinoma subgroup and the ductal adenocarcinoma subgroup based on pathological typing. Data including age, gender, preoperative CA19-9 level, surgical margin status, lymph node metastasis, pathological grade, T stage, postoperative adjuvant chemotherapy, and survival follow-up were recorded. The median follow-up time was 35.00 months for IC-Ds patients and 29.00 months for C-PDACs patients. Clinicopathological characteristics and prognostic factors were compared between the IC-Ds and C-PDACs groups, as well as between the colloid carcinoma and ductal adenocarcinoma subgroups. Kaplan-Meier curves for overall survival were generated. Results:There were no significant differences in age, gender, R1 resection margin between the IC-Ds group and the C-PDACs group. However, in the C-PDACs group, 70 cases (74.47%) had elevated preoperative CA19-9, 40 cases (42.55%) had lymph node metastasis, 25 cases (26.60%) were pathologically confirmed as poorly differentiated carcinoma after surgery, and 54 cases (57.45%) received postoperative adjuvant chemotherapy; the proportions of all these indicators were higher than those in the IC-Ds group (90/288, 31.25%; 72/288, 25.00%; 32/288, 11.11%; 105/288, 36.46%). In contrast, the proportion of T1 stage in the IC-Ds group was higher (40.97% vs 20.21%), and all these differences were statistically significant (all P value <0.05). Among the 288 patients in the IC-Ds group, 97 cases (33.68%) were colloid carcinoma and 191 cases (66.32%) were ductal adenocarcinoma. There were no significant differences in age, gender, R1 resection margin, proportion of poorly differentiated carcinoma between the two subgroups. However, in the ductal adenocarcinoma subgroup, 67 cases (35.08%) had elevated preoperative CA19-9, 56 cases (29.32%) had lymph node metastasis confirmed by postoperative pathology, and 80 cases (41.88%) received postoperative adjuvant chemotherapy; all these proportions were significantly higher than those in the colloid carcinoma subgroup (23/97, 23.71%; 16/97, 17.02%; 25/97, 26.60%). In addition, the ductal adenocarcinoma subgroup had higher proportions of T2 and T3/T4 stages, while the proportion of T1 stage in the colloid carcinoma subgroup (60/97, 61.86%) was significantly higher than that in the ductal adenocarcinoma subgroup (58/191, 30.37%), with all differences being statistically significant (all P value <0.05). The median survival time was 47.00 months (95% CI 42.91-51.09) in the IC-Ds group and 34.00 months (95% CI 29.67-38.33) in the C-PDACs group. For the IC-Ds subgroups, the median survival time was 59.00 months (95% CI 50.79-67.21) in the colloid carcinoma subgroup and 42.00 months (95% CI 35.15-48.85) in the ductal adenocarcinoma subgroup. Significant differences in median survival time were observed between the IC-Ds and C-PDACs groups, between the colloid carcinoma and ductal adenocarcinoma subgroups, and between the ductal adenocarcinoma subgroup and the C-PDACs group (all P value <0.01). Conclusions:IC-Ds has a better prognosis than C-PDACs, and there is significant heterogeneity within IC-Ds, indicating different biological behaviors between the two types, which requires the development of targeted diagnosis and treatment strategies.