Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

This study was performed to investigate the inhibitory effects of Xuebijing injection(XBJ)on lipopolysaccharide(LPS)-induced inflammatory signals on EA.hy926 vascular endothelial cells and the underlying mechanism,and to provide a theoretical basis for the treatment of sepsis with XBJ.WST-1 assay was used to detect the effects of XBJ on the cell viability;Western blot analysis was performed to detect the protein expression levels of IκBα,p-p65,p-ERK,p-JNK,p-p38,p-AMAD17 in cell lysates and the content of sTLR4 fragment in the concentrated culture supernatants.ADAM17 sheddase activity in cells was detected by using a commercial available kit.Data showed that all of the TLR4-mediated inflammatory signals were significantly inhibited by the treatment of XBJ(P＜0.01).ADAM17 phosphorylation and shedding activity were induced by XBJ treatment,simultaneously the sTLR4 contents in the culture media were increased.XBJ-induced shedding of TLR4 was suppressed by the preteatment of 10 μmol/L TAPI-1(an ADAM17 inhibitor).Taken together,XBJ can induce the shedding of TLR4 from cell membrane by up-regulating ADAM17 shedding activity,thereby inhibiting the activation of TLR4-mediated intracellular inflammatory signals in EA.hy926 cells.

Objective:To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease.Methods:In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed.Results:There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) ( P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased ( P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased ( P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group ( P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis ( P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection ( P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95% CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion:The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

Objective:To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease.Methods:In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed.Results:There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) ( P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased ( P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased ( P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group ( P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis ( P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection ( P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95% CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion:The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

Objective To investigate the safety and efficacy of ciprofol combined with oxycodone in elderly patients who underwent endoscopic gastric mucosal dissection.Methods A total of 204 elderly patients in the outpatient department of the Northern Theater General Hospital who were to undergo endoscopic gastric mucosal dissection from March 2022 to December 2022 were selected as study participants.They were aged 60-75 years,with a body mass index of 18-30 kg/m2,and ASA grade Ⅱ or Ⅲ,regardless of sex.They were randomly divided into propofol(group P),ciprofol(group C),and ciprofol+oxycodone(group CO)groups,with 68 patients in each group.During anesthesia induction,group P was given propofol(1-1.5 mg/kg);group C,ciprofol(0.2-0.5 mg/kg);and group CO,oxyco-done hydrochloride(0.1-0.2 mg/kg)and ciprofol(0.2-0.5 mg/kg).The injection time of the three groups was>30 s.During anesthesia maintenance,ciprofol[1-1.5 mg/(kg·h)]was continuously injected intravenously in groups C and CO,and propofol[2-5 mg/(kg·h)]was continuously injected intravenously in group P.The modified observer's assessment of alertness/sedation score was evaluated at 3 min after anesthesia induction.If the score was≤1,endoscopy was started.The mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO2)at times T0(before drug injection),T1(when eyelash reflex disappeared),T2(when endoscopy began),and T3(when endoscope was withdrawn);visual analogue scale(VAS)scores at 30 min and 1 h after resuscitation;and induction time,recovery time,intravenous pain,respiratory depression,and other adverse reactions were recorded in the three groups.Results There were no significant differences in MAP,HR,and SpO2 at T0 and T3 among the three groups(all P>0.05).At T1 and T2,compared with those in group P,MAP,HR,and SpO2 in groups C and CO were significantly increased(all P<0.05).MAP,HR,and SpO2 in the CO group were slightly lower than those in the C group;however,the differences were not statistically significant(all P>0.05).Compared with that in group P,the incidence of respiratory depression and injection pain in groups C and CO was significantly reduced(P<0.05),but there was no statistically significant difference between groups C and CO(P>0.05).The VAS score at 30 min and 1 h after awakening and inci-dence of body movement in the CO group were lower than those in the P and C groups(all P<0.05);however,there was no statistically significant difference between the P and C groups(all P>0.05).Conclusion Ciprofol combined with oxycodone had definite sedative and analgesic effects in elderly patients undergoing endoscopic gastric mucosal dissection.Compared with the use of propofol or ciprofol alone,with combination therapy,the respiratory cycle is more stable,patients have fewer adverse reactions,and it is worthy of clinical application.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

The in-depth study of the intervention of endometriosis （EMS） with Chinese medicines has revealed many pathways that can be regulated by Chinese medicines in the treatment of EMS. Chinese medicinal compound prescriptions， single Chinese herbal medicines， or their active ingredients treat EMS via the signaling pathways discussed in this paper. They can directly or indirectly regulate the expression of key molecules in the corresponding signaling pathways to inhibit the proliferation of endometriotic cells and the inflammatory changes of endometrial tissue， promote the apoptosis of endometriotic cells， change the pain threshold， and reduce endometriotic cell invasion， so as to achieve the therapeutic effects of inhibiting EMS progression， improving endometrial receptivity， and reducing ovarian injury. The following details are based on relevant studies conducted both at home and abroad. Curcumol can inhibit angiogenesis and promote cell apoptosis by blocking the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Icariin can reduce inflammation and promote cell apoptosis by blocking the nuclear factor-kappa B signaling pathway. Puerarin can suppress cell proliferation and promote cell apoptosis by inhibiting the mitogen-activated protein kinase （MAPK） signaling pathway and blocking the estrogen signaling pathway. Naringenin has the ability to activate the MAPK signaling pathway to promote cell apoptosis. Imperatorin can inhibit cell proliferation and promote cell apoptosis by inhibiting the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Resveratrol can inhibit cell proliferation and alleviate fibrosis and adhesion by blocking the transforming growth factor-beta signaling pathway. Paeonol can inhibit angiogenesis by blocking the hypoxia-inducible factor 1 signaling pathway. The above summary can serve as a reference for the future clinical treatment or experimental research of EMS with Chinese medicines.

Objective:To investigate the value of a nomogram predicting the outcome of intracerebral hemorrhage (ICH) based on clinical characteristics and diffusion-weighted imaging (DWI) of hyperintense lesions.Methods:A case-control study. Consecutive patients, aged 30-88(59±13) years old, with ICH were recruited at the Stroke Center of Zhengzhou People′s Hospital from January 2018 to August 2021. Patients were divided into a group with DWI lesions and a group without DWI lesions depending on whether there were DWI hyperintense lesions distant from the hematoma. Prognosis was evaluated at 90 days via the modified Rankin Scale (mRS). Univariate and multivariable logistic regression models were used to identify independent predictors of a poor ICH outcome (mRS score≥4), and a nomogram model was developed. The performance of the nomogram was validated via the area under the receiver operating characteristic curve (AUC) and a calibration chart.Results:Of the 303 patients included in the study, 24.8% presented with DWI lesions; 17.5% with asymptomatic DWI lesions and 7.3% with symptomatic DWI lesions. Poor outcomes were significantly more frequent in the group with DWI lesions than in the group without DWI lesions ( χ2=21.32, P<0.001). In multivariable regression analysis, age [odds ratio ( OR)=1.032, 95% confidence interval ( CI) 1.002-1.063, P=0.035], hematoma volume ( OR=1.050, 95% CI 1.011-1.090, P=0.012), hematoma location ( OR=3.839, 95% CI 1.248-11.805, P=0.019), DWI lesions ( OR=3.955, 95% CI 1.906-8.206, P<0.001), and baseline NIHSS scores ( OR=1.102, 95% CI 1.038-1.170, P=0.001) were independent predictors of a poor outcome. In subgroup analysis patients with asymptomatic DWI lesions had a 3-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=3.135, 95% CI 1.382-7.112, P=0.006), and patients with symptomatic DWI lesions had a 7-fold greater risk of a poor outcome compared to those without DWI lesions ( OR=7.126, 95% CI 2.279-22.277, P=0.001). A nomogram model was established based on the independent predictors for a poor outcome. The AUC of the nomogram was 0.846 (95% CI 0.795-0.898), and a calibration chart indicated good consistency between values predicted by the nomogram and actual observed values. Conclusions:DWI lesions are an independent risk factor for a poor outcome in patients with ICH-particularly symptomatic DWI lesions. A nomogram model based on clinical characteristics and DWI lesions exhibited good efficacy when predicting the outcome of ICH.

Acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) accounts for about 20% of all patients with AIS. Endovascular treatment (EVT) is the gold standard for the treatment of LVO-AIS. It is necessary to evaluate the cerebral hemodynamics after EVT, and individualized blood pressure and cerebral blood flow management can be carried out accordingly. Transcranial Doppler ultrasound (TCD) is a method that can evaluate the changes of cerebral hemodynamics in real time at the bedside. It has the advantages of being reliable, safe, cheap, and non-invasive. This article reviews the predictive role of TCD in patients with AIS treated with EVT