ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

OBJECTIVE To observe the isolation rates and drug resistance rates of Acinetobacter baumannii strains isolated from intensive care unit(ICU)patients in 8 consecutive years so as to provide bases for reasonable clinical application of antibiotics and control of infections.METHODS The isolation rates and specimens from which the A.baumannii and carbapenem-resistant A.baumannii(CRAB)strains were isolated from ICU patients of the First People's Hospital of Changzhou between 2017 and 2024 were retrospectively analyzed.The trends of the drug resistance rates were observed.RESULTS Totally 2078(18.03％)strains of A.baumannii were isolated from the ICU patients from 2017 to 2024,and there was no significant difference in the changing trend among the years(x2=-1.573,P=0.116).Among the A.baumannii strains that were isolated from 2017 to 2024,58.08％were isolated from sputum,and 24.25％from lavage fluid specimens;the percentage of sputum specimens showed a downward trend in the 8 years(x2=-8.257,P＜0.001),while the percentage of lavage fluid speci-mens showed an upward trend(x2=12.964,P＜0.001).The isolation rate of the CRAB strains was 91.48％in 2017,92.61％in 2018,92.56％in 2019,82.53％in 2020,52.44％in 2021,showing a down-ward trend,and it began to rise in 2022-2024,there was significant difference(x2=-2.277,P=0.012).The isolation rates of the CRAB strains from both sputum and lavage fluid specimens showed downward trends and then upward trends(all P＜0.05).The drug resistance rates of the A.baumannii strains to piperacillin and minocycline showed slow upward trends,while the drug resistance rates to gentamicin and tigecycline showed downward trends,and there were significant differences(P＜0.05).The drug resistance rates of the A.bau-mannii strains to imipenem and meropenem remained more than 90％.CONCLUSIONS Acinetobacter spp is the major pathogen causing the hospital-acquired infection.The isolation rate of CRAB strains shows a downward trend then a upward trend in recent two years.It is necessary for the hospital to standardize the submission of spu-tum specimens and increase the aseptic submission.The A.baumannii strains show high drug resistance rates to the commonly used antibiotics.Polymyxin B,tigecycline and minocycline are the major antibiotics for treatment of CRAB infection.

Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Objective To explore the changes of core symptoms and nursing strategies for lymphoma patients during chemotherapy using a dynamic network analysis model,and provide a reference for precise symptom intervention.Methods A longitudinal study was conducted,and lymphoma patients undergoing chemotherapy in the Department of Lymphoma at a tertiary hospital in Tianjin from September 2021 to December 2023 were conveniently sampled.The Lymphoma Patient Symptom Assessment Scale was used to track symptoms at 3 time points:7 to 14 days after the 1st treatment cycle(T1),the 3rd cycle(T2),and the 6th cycle(T3).Dynamic symptom network analysis,including network relationships,core symptoms,and bridge symptoms,was performed using R software.Results During the research process,135 participants withdrew,resulting in a final inclusion of 865 cases for analysis.Fatigue exhibited the highest incidence rate(34.80％)at T1;alopecia was the most prevalent symptom(58.03％and 53.64％,respectively)at T2 and T3.The T1→T2 dynamic network analysis showed that fever had the highest out-expected influence(EI=0.551)and bridge expected influence(EI=0.225).The T2→T3 dynamic network analysis showed that limb numbness exhibited the highest out-expected influence(EI=0.203)and bridge-expected influence(EI=0.170).Reliability tests indicated that both dynamic networks demonstrated moderate accuracy but suboptimal stability.Conclusion Fatigue was the most common symptom at T1;alopecia was the most prevalent symptom at T2 and T3.Fever was the core symptom and bridging symptom in the T1→T2 symptom network,whereas limb numbness assumed the role of the core symptom and bridging symptom in the T2→T3 symptom network.The clinical practitioners could take high-incidence symptoms and core symptoms as intervention targets to develop precise symptom management strategies for lymphoma patients undergoing chemotherapy.

BACKGROUND:Adolescent lumbar disc herniation is the main cause of low back pain in adolescents. At present,most of them are treated by conservativetreatment. When long-term non-surgical treatment attempts,surgery may be necessary to prevent further injury when the patient's symptoms are notsufficiently relieved or when the patient has symptoms of single nerve paralysis or compression of the cauda equina,it is very important to choose a suitable interbody fusion device for the surgical treatment of the patients.OBJECTIVE:To explore the effects of minimally invasive interbody fusion with different heights on lumbar biomechanics in patients with adolescent lumbar disc herniation.METHODS:CT scans of a 17-year-old male patient with adolescent lumbar disc herniation (L4-5 segment herniation) were collected. After the three-dimensional reconstruction of MIMICS,the interbody fusion device equal to and 3 mm higher than the intervertebral space was selected for analysis,so two expandablemixed material interbody fusion devices were designed and reconstructed. Fusion device L:11 mm high front,9 mm high posterior,9 mm wide,28 mmlong,and fusion device H:14 mm high front,11 mm high posterior,11 mm wide,28 mm long and the lumbar fusion device was modeled. The fusion deviceand lumbar spine model were optimized,inversely modeled,and then imported into ABAQUS,and finally the 3D model of lumbar fusion was obtained.The physiological activities of the human body were simulated,such as lumbar extension,forward bending,right bending,and left bending,to obtain thecorresponding stress contours. The biomechanical characteristics of the L4-5 vertebra under seven different working conditions were observed.RESULTS AND CONCLUSION:(1) The maximum stress of the two kinds of fuses was in the condition of forward bending and backward extension,the stress value of H fuses was (18.27±3.80) Mpa and (15.02±3.24) Mpa;the stress value of L fuses was (9.16±0.05) Mpa and (9.17±1.83) Mpa. The stress values of the end plate of the H-fusion in the extension station were (19.11±4.03) Mpa and (16.32±3.72) Mpa respectively. The stress values of the L-fusion end plate were (9.13±0.01) Mpa and (4.92±1.01) Mpa respectively. (2) The stress of H-type fusing end plate was higher than that of L-type fusing end plate except for L-5 end plate at neutral position (P<0.05). (3) Choosing an interbody fusion device with a height of more than 3 mm in the same intervertebral space has a more stable biomechanics.

OBJECTIVE To observe the isolation rates and drug resistance rates of Acinetobacter baumannii strains isolated from intensive care unit(ICU)patients in 8 consecutive years so as to provide bases for reasonable clinical application of antibiotics and control of infections.METHODS The isolation rates and specimens from which the A.baumannii and carbapenem-resistant A.baumannii(CRAB)strains were isolated from ICU patients of the First People's Hospital of Changzhou between 2017 and 2024 were retrospectively analyzed.The trends of the drug resistance rates were observed.RESULTS Totally 2078(18.03％)strains of A.baumannii were isolated from the ICU patients from 2017 to 2024,and there was no significant difference in the changing trend among the years(x2=-1.573,P=0.116).Among the A.baumannii strains that were isolated from 2017 to 2024,58.08％were isolated from sputum,and 24.25％from lavage fluid specimens;the percentage of sputum specimens showed a downward trend in the 8 years(x2=-8.257,P＜0.001),while the percentage of lavage fluid speci-mens showed an upward trend(x2=12.964,P＜0.001).The isolation rate of the CRAB strains was 91.48％in 2017,92.61％in 2018,92.56％in 2019,82.53％in 2020,52.44％in 2021,showing a down-ward trend,and it began to rise in 2022-2024,there was significant difference(x2=-2.277,P=0.012).The isolation rates of the CRAB strains from both sputum and lavage fluid specimens showed downward trends and then upward trends(all P＜0.05).The drug resistance rates of the A.baumannii strains to piperacillin and minocycline showed slow upward trends,while the drug resistance rates to gentamicin and tigecycline showed downward trends,and there were significant differences(P＜0.05).The drug resistance rates of the A.bau-mannii strains to imipenem and meropenem remained more than 90％.CONCLUSIONS Acinetobacter spp is the major pathogen causing the hospital-acquired infection.The isolation rate of CRAB strains shows a downward trend then a upward trend in recent two years.It is necessary for the hospital to standardize the submission of spu-tum specimens and increase the aseptic submission.The A.baumannii strains show high drug resistance rates to the commonly used antibiotics.Polymyxin B,tigecycline and minocycline are the major antibiotics for treatment of CRAB infection.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.