BACKGROUND:Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis,and Hemin can regulate the expression of mitochondria-related proteins. OBJECTIVE:To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS:(1)In vitro cell experiment:Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis.The optimal concentration of Hemin(0,1,10,20,40,80,and 160 μmol/L)for the intervention in mouse chondrocytes was determined by cell counting kit-8 method.Chondrocytes were randomly divided into control group,model group(interleukin-1β)and Hemin group(interleukin-1β+Hemin).Reactive oxygen species,mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected.(2)In vivo experiment:Adult C57BL/6 mice were randomly divided into normal group,model group(osteoarthritis)and Hemin group(osteoarthritis+Hemin),with eight mice in each group.After 4 weeks of Hemin treatment,the behavioral test and histopathological observation of the knee joint were performed in each group.Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION:In vitro experiment:the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L.Compared with the model group,the level of reactive oxygen species was significantly reduced,the mitochondrial membrane potential was significantly improved,and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes.In vivo experiment:After 4 weeks of treatment,compared with the model group,the lower limb function of mice in the Hemin group was significantly improved,the histopathological score was significantly improved,and the apoptosis of knee chondrocytes was significantly reduced.All these findings indicate that Hemin can alleviate oxidative stress,restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β.Hemin can improve extracellular matrix degradation,promote chondrocyte anabolism,reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis.It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment.

Diabetic macular edema(DME), a serious complication of diabetic retinopathy(DR), is a chronic condition caused by multiple factors. Throughout its progression, inflammatory factors and vascular endothelial growth factor(VEGF)play a critical role. Anti-VEGF drugs have shown significant effectiveness in the treatment of DME; however, some patients may experience persistent DME after injection or require frequent injections. Dexamethasone intravitreal implants(DEX implants)serve as a sustained-release implant characterized by a reasonable release profile and high bioavailability. They offer safe, effective, and prolonged anti-inflammatory effects, aiding in the repair of retinal barrier and reduction of exudation. To further enhance patients' visual quality, exploring the efficacy of DEX implants in combination with existing treatment regimens has great clinical significance. This review primarily discusses the research advancements in DEX implants, focusing on their pharmacological properties, indications for use, and their combination with existing drugs and treatment methods. It also evaluates the advantages and disadvantages of combination therapy or switching to DEX implants compared to current standard treatments, aiming to provide guidance for personalized treatment options for patients with DME.

OBJECTIVE: To evaluate early effectiveness of posterior 180-degree decompression via unilateral biportal endoscopy (UBE) in the treatment of lumbar spinal stenosis (LSS) combined with Michigan State University (MSU)-1 lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on clinical data from 33 patients with LSS combined with MSU-1 LDH, who met selection criteria and were treated between March 2022 and January 2024. All patients underwent UBE-assisted 180-degree spinal canal decompression. The cohort comprised 17 males and 16 females, aged 37-82 years (mean, 67.1 years). Preoperative presentations included bilateral lower limbs intermittent claudication and radiating pain, with disease duration ranging from 5 to 13 months (mean, 8.5 months). Affected segments included L _{3, 4} in 4 cases, L _{4, 5} in 28 cases, and L ₅, S ₁ in 1 case. LSS was rated as Schizas grade A in 4 cases, grade B in 5 cases, grade C in 13 cases, and grade D in 11 cases. LDH was categorized as MSU-1A in 24 cases, MSU-1B in 2 cases, and MSU-1AB in 7 cases. Intraoperative parameters (operation time, blood loss) and postoperative hospitalization length were recorded. The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to assess the lower limb pain and functional outcomes after operation. Clinical efficacy was evaluated at last follow-up via modified MacNab criteria. Quantitative radiological assessments included dural sac cross-sectional area (DSCA) measurements and spinal stenosis grading on lumbar MRI. Morphological classification of lumbar canal stenosis was determined according to the Schizas grading, categorized into four grades. RESULTS: The operation time was 60.4-90.8 minutes (mean, 80.3 minutes) and intraoperative blood loss was 13-47 mL (mean, 29.9 mL). The postoperative hospitalization length was 3-5 days (mean, 3.8 days). All patients were followed up 12-16 months (mean, 13.8 months). The VAS score and ODI improved at immediate and 3, 6, and 12 months after operation compared to before operation, and the differences between different time points were significant ( P<0.05). At last follow-up, the clinical efficacy assessed by the modified MacNab criteria were graded as excellent in 23 cases, good in 9 cases, and poor in 1 case, with an excellent and good rate of 96.97%. Postoperative lumbar MRI revealed the significant decompression of the dural sac in 32 cases, with 1 case showing inadequate dural expansion. DSCA measurements confirmed progressive enlargement and stenosis reduction over time. The differences were significant ( P<0.05) before operation, immediately after operation, and at 6 months after operation. At 6 months after operation, Schizas grading of spinal stenosis improved to grade A in 27 cases and grade B in 6 cases. CONCLUSION Posterior 180-degree decompression via UBE is a safe and feasible strategy for treating LSS combined with MSU-1 LDH, achieving effective neural decompression while preserving intervertebral disc integrity.
Humans ; Spinal Stenosis/diagnostic imaging* ; Male ; Female ; Aged ; Lumbar Vertebrae/surgery* ; Middle Aged ; Intervertebral Disc Displacement/complications* ; Decompression, Surgical/methods* ; Retrospective Studies ; Endoscopy/methods* ; Adult ; Aged, 80 and over ; Treatment Outcome

Osteoarthritis(OA)mainly lies in the lesions of articular cartilage and surrounding tissues,pro-ducing osteophytes and bone sclerosis,resulting in damage to the articular cartilage.The main pathological mechanism of OA rests with a large number of inflammatory cytokines and inflammatory mediators produced by joint synovial lesions as well as pathological vascular growth at the junction of the synovium and cartilage,which may be one of the key reasons for promoting synovitis and cartilage damage.The OA mainly occurs in the knees,hips,hands and the spine.It is mainly manifested by chronic joint pain,swelling and stiffness,and limitation of motion seriously affects the functional activities of patients.The treatment of OA mainly relies on oral administration or intraarticular injection of drugs to relieve symp-toms.When OA develops to the middle and late stages,the action and life of patients will be seriously affected.There-fore,surgical replacement of joints is considered to ensure the basic life demands of patients.Studies show that traditional Chinese medicine(TCM)treatment has attracted widespread attention and application due to its unique advantages in pre-vention and treatment of OA.Janus kinase(JAK)/signaling transduction and transcriptional activator(STAT)signaling pathway may be one of the important signaling pathways that regulate the chondrocyte proliferation,differentiation and apoptosis.Moreover,it is closely associated with intra-articular inflammatory response.The JAK/STAT signaling pathway regulates the expression of inflammatory factors and related proteins through TCM so as to reduce the inflammatory re-sponse and decrease the chondrocyte damage.It has an important reference value for OA treatment.In this paper,the roles and mechanisms of the TCM monomers and active ingredients and the Chinese herbal compounds in OA by regulating JAK/STAT signaling pathway and affecting related cytokine and protein expression levels have been reviewed,providing a new method and direction for TCM treatment of OA.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective:To analyze the effects of preoperative renin-angiotensin system inhibitor (RASi) use on postoperative renal function and short-term and long-term prognosis in patients undergoing coronary artery bypass grafting (CABG).Methods:A retrospective cohort analysis was conducted. Based on the registration study data of CABG patients at Fuwai Hospital, Chinese Academy of Medical Sciences, the clinical data of adult patients who underwent CABG from January 2013 to December 2022 were analyzed. Preoperative use of RASi (PreRASi) was defined as receiving RASi treatment within 48 hours before surgery. Postoperative acute kidney injury (AKI) was defined using the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO). Demographic characteristics, past medical history, comorbidities, preoperative medication, preoperative laboratory test results, specific information on surgical procedures, and postoperative treatment related data were extracted. The primary endpoint was the incidence of postoperative AKI. Secondary endpoints included in-hospital all-cause mortality and all-cause mortality within the longest follow-up period. According to whether RASi was used before surgery, the patients were divided into PreRASi group and No-PreRASi group. The baseline data of the two groups were balanced by propensity score matching (PSM). Logistic regression model and Cox proportional hazards model were used to assess the correlation between PreRASi and postoperative AKI and clinical outcomes, and analyze the subgroups of hypertension and heart failure with preserved ejection fraction (HFpEF) in the cohort.Results:A total of 33?884 patients who underwent CABG were included, with a mean follow-up duration of (3.0±2.4) years and the longest follow-up duration up to 8.5 years. There were 9?128 cases (26.94%) in the PreRASi group and 24?756 cases (73.06%) in the No-PreRASi group. The incidence of postoperative AKI in the PreRASi group was 47.61% (4?346 cases), compared to 52.37% (12?964 cases) in the No-PreRASi group. Two groups were matched with 5?094 patients each. Compared to the No-PreRASi group, both before and after PSM, PreRASi was associated with a reduction of risk of postoperative AKI [before PSM: odds ratio ( OR) = 0.834, 95% confidence interval (95% CI) was 0.793-0.877, P < 0.001; after PSM: OR = 0.875, 95% CI was 0.808-0.948, P = 0.001]. Subgroup analysis of hypertensive and HFpEF patients showed that PreRASi was associated with a decreased risk of postoperative AKI before and after PSM. The in-hospital mortality for the PreRASi and No-PreRASi groups were 0.61% (56 cases) and 0.49% (121 cases), respectively. Analysis of the overall cohort and subgroups with hypertension and HFpEF showed no correlation between PreRASi and in-hospital mortality or longest follow-up mortality. Conclusion:The perioperative use of RASi can reduce the risk of postoperative AKI in patients undergoing CABG, has a certain renal protective effect, but is not associated with short-term or long-term death risk after surgery.

Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability.Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin.ApoE-/-mice were fed with high-fat diet and received naringenin by lavage for 16 weeks.Intraplaque nec-rotic core,contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining.Elastin was detected by Van Gieson staining.Matrix metalloproteinase(MMP)activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin(50 μmol/L)increased signal tansducer and activator of transciption 6(STAT6)phosphorylation and promoted tissue inhibitor of metalloproteinase-3(TIMP-3)expression by 3.1-fold(P＜0.001).After naringenin(80 mg/kg)treatment,compared with the control group,the area of plaque necrotic core in aor-tic root decreased by 53％(P＜0.01),the thickness of fibrous caps increased by nearly 50％(P＜0.05),and the degree of elastic fiber degradation decreased.At the same time,naringenin promoted the expression of TIMP-3 in plaques,and corre-spondingly reduced the activity of MMP in plaques.Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability.Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells,improve the composition of extracellular matrix,and promote the stability of atherosclerotic plaque.

The incidence of ischemic stroke in the pregnancy is low and the mortality is high. The clinical and imaging data of a pregnant woman with atrial septal defect complicated with stroke after awakening were reviewed to explore the imaging manifestations, pathogenesis and treatment strategy of pregnancy-related stroke. The aim of this study was to improve the understanding of acute stroke in pregnant women with atrial septal defect, and to provide reference for clinical diagnosis and treatment.

Objective:To investigate the serum and follicular fluid levels of sterol regulatory element-binding protein 1c(SREBP-1c), leucine-rich α-2-glycoprotein 1(LRG1) and the correlation with insulin resistance(IR) in non-ovarian etiology infertility patients and polycystic ovary syndrome(PCOS) patients with or without IR.Methods:Forty-nine PCOS patients and 66 infertility patients with non-ovarian etiology were collected in this retrospective study, homeostasis model assessment for insulin resistance(HOMA-IR) was used to evaluate IR, and were divided into control group( n=36), IR group( n=30), PCOS alone group( n=28) and PCOS-IR group(PCOS with IR group, n=21). The concentrations of serum, follicular fluid LRG1 and SREBP1c levels in each group were compared, and their correlation with relevant hormones and glycolipid metabolism were analyzed. Results:The levels of serum, follicular fluid LRG1 and SREBP1c in IR group, PCOS alone group and PCOS-IR group were significantly higher than those in control group; The PCOS-IR group showed a more significant increase in the levels of serum, follicular fluid LRG1 and SREBP1c( P<0.05). Correlation analysis showed that serum, follicular fluid LRG1 was positively correlated with body mass index, fasting plasma glucose(FPG), fasting insulin(FINS), triglycerides(TG), and HOMA-IR( P<0.05). Serum, follicular fluid SREBP1c was positively correlated with body mass index, FPG, FINS, TG, total cholesterol, LDL-C, LH, total teststerone, DHEAS, FAI, and HOMA-IR( P<0.05). Binary logistic regression analysis showed that serum SREBP1c was a risk factor for PCOS( P<0.05). Conclusion:The serum and follicular fluid levels of LRG1 and SREBP-1c were elevated in PCOS patients, especially in those with IR. The elevated levels of serum and follicular fluid LRG1 and SREBP-1c may be associated with IR and glucose-lipid metabolism abnormalities in PCOS patients. Serum LRG1 and SREBP-1c levels may serve as new indicators for predicting IR, early diagnosis, and intervention in PCOS patients.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.