Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Objective:To investigate the application effect of curved incision surgery in the treatment of hammock finger tendon.Methods:45 patients with hammock finger tendon who were admitted to Pingle Orthopedics and Traumatology Hospital in Shenzhen were selected from May 2022 to May 2023,all of whom were treated with curved incision surgery.Wound healing,functional recovery and complication rate were observed after surgery.Results:In this study,45 patients with hammock finger tendon were successfully followed up for 3 to 18 months,with an average follow-up of 1 year.The results of follow-up showed that all the incisions healed in one stage,and there were no complications such as skin infection and necrosis,exposed knots and skin irritation.X-ray reexamination before and after the operation showed,no complications such as loosening of the Kirkner needle,redisplacement of bone mass and nonunion of bone.During the follow-up period,there was no significant recurrence of vertical deformity.Crawford grading showed that,35 cases were excellent,9 were good,and 1 was fair.Conclusion:Using curved incision surgery to treat hammock finger tendon,which has the advantages of less trauma,faster recovery and fewer complications,and the effect is good.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: To analyze the clinical efficacy and safety of microsurgery in patients with Gustilo ⅢC open fractures. METHODS: A total of 64 patients with Gustilo ⅢC open fractures who were admitted to the hospital bewteen September 2018 and March 2022 were included, and divided into the observation group and the control group, with 32 cases in each one. In the observation group, there were 24 males and 8 females, aged from 29 to 42 years with an average of (36.59±3.24) years. The tibial defect ranged from 2 to 5 cm with an average of (3.41±0.61) cm, and the soft tissue defect area ranged from 34 to 76 cm2 with an average of (58.50±9.44) cm2. This group received microsurgical treatment. In the control group, there were 25 males and 7 females, aged from 27 to 44 years with an average of (37.59±3.21) years. The tibial defect ranged from 2 to 6 cm with an average of (3.59±0.80) cm, and the soft tissue defect area ranged from 36 to 78 cm2 with an average of (59.09±9.53) cm2. This group received conventional staged surgery, with plaster or brace fixation after initial debridement and appropriate internal fixation at a later stage. The Anderson scores, motor ability Fugl-Meyer scale, perioperative indicators, rehabilitation outcomes, and complications were compared between the two groups. RESULTS: The patients were followed up for a duration from 2.5 to 5.5 months with an average of (3.15±1.11) months. In the observation group, 19 patients were rated as excellent, 12 patients as good, 1 patient as fair, and no patients as poor. In the control group, 11 patients were rated as excellent, 13 patients as good, 6 patients as fair, and 2 patients as poor. The difference in outcomes between the two groups was statistically significant (P<0.05). The operation time, the hospitalization time, and the hospitalization cost in the observation group(4.39±0.69) h, (30.22±4.58) d, and (23, 500±3, 300) yuan, respectively were significantly lower than those in the control group(5.01±0.75) h, (33.28±3.74) d, and(30, 200±5, 200) yuan, respectively (P<0.05). Revascularization time(134.25±14.76) h, wound healing time(11.34±1.56) d, and fracture healing time(3.09±0.42) months in the observation group were significantly shorter than those in the control group(P<0.05) which were (189.36±22.17) h, (13.22±2.03) d and (4.02±0.57) months respectively. The motor ability(42.91±5.51) points, sensory function(46.19±3.53) points, and total Fugl-Meyer score(89.09±6.08) in the observation group were significantly higher than those in the control group(P<0.05) which were(35.19±4.27), (34.03±3.79), (69.22±6.32) points respectivdy. In the observation group, there were 1 case of refractory wound and 3 cases of complete nerve injury, which were lower than those in the control group (8 cases and 10 cases, respectively, P<0.05). The number of complications in the observation group was lower than that in the control group (P<0.05). CONCLUSION Microsurgical technique can effectively shorten the wound and fracture healing time in patients with Gustilo Ⅲ C open fracture, improve limb movement ability, and reduce the risk of poor prognosis and complications.
Humans ; Male ; Female ; Adult ; Fractures, Open/surgery* ; Microsurgery/methods* ; Treatment Outcome