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.

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 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.

Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

OBJECTIVE: To observe the clinical effect of acupuncture at yinsanzhen combined with auricular point sticking on primary dysmenorrhea (PDM). METHODS: Sixty patients with PDM were randomly divided into an observation group and a control group, with 30 cases in each group. Patients in the observation group were treated with acupuncture at yinsanzhen combined with auricular point sticking. The acupuncture was given at yinsanzhen (Guanyuan [CV4] and bilateral Guilai [ST29], Sanyinjiao [SP6]) once daily for 5 consecutive days. Auricular point sticking was applied to gan (CO₁₂), shen (CO₁₀), neifenmi (CO₁₈), etc. every other day, alternated between ears, totaling 3 sessions. All treatments were started 5 days before menstruation. Patients in the control group were treated with ibuprofen sustained-release capsules on the first day of menstruation for 3 consecutive days. Both groups were treated for 3 menstrual cycles. The scores of Cox menstrual symptom scale (CMSS) and visual analogue scale (VAS) were compared between the two groups before and after treatment and at the second menstrual cycle after treatment completion (follow-up). The serum contents of prostaglandin (PG) F2α and PGE2 were detected before and after treatment, and the clinical effect and safety of the two groups were evaluated. RESULTS: After treatment and during follow-up, the CMSS severity and duration scores and VAS scores of the two groups were lower than those before treatment (P<0.05 ), and the scores in the observation group were lower than those in the control group (P<0.05). After treatment, the serum contents of PGF2α were decreased, and the contents of PGE2 were increased (P<0.05) in the two groups. The total effective rate of the observation group was 93.3% (28/30), which was higher than 80.0% (24/30) of the control group (P<0.05). There were no adverse reactions in both groups. CONCLUSION Yinsanzhen combined with auricular point sticking can effectively improve the pain symptoms, relieve the degree of pain and shorten the duration of pain in patients with PDM, which may play a therapeutic role by reducing the content of serum PGF2α and increasing the content of serum PGE2.
Humans ; Female ; Dysmenorrhea/therapy* ; Acupuncture Points ; Adult ; Young Adult ; Acupuncture, Ear ; Treatment Outcome ; Adolescent ; Acupuncture Therapy ; Combined Modality Therapy

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.