BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.

Objective To analyze the clinical characteristics and prognosis of patients with thalamic infarction.Methods The clinical data of 47 patients with simple thalamic infarction hospitalized in Beijing Shuili Hospital from January 2016 to January 2022 were retrospectively analyzed.Cranial magnetic resonance imaging and diffusion weighted imaging were used to determine the infarct area of the thalamus,and the clinical characteristics and prognosis of patients with different thalamic infarction regions were observed.Results Among 47 patients with simple thalamic infarction,there were 4 cases of anterior nucleus infarction,22 cases of lateral nucleus infarction,13 cases of medial nucleus infarction and 8 cases of posterior nucleus infarction.The most common clinical manifestations were contralateral hemiplegia,hemidysesthesia and memory impairment.The clinical prognosis of patients with lateral nucleus,anterior nucleus and posterior nucleus infarcts was better,and the prognosis of patients with medial nucleus infarcts was worst.At 90 days of follow-up,the scores of the modified Barthel index were significantly higher than those at admission(P<0.05).Conclusion Patients with thalamic infarction were prone to clinical manifestations such as hemiplegia,hemidysesthesia and memory impairment,but the overall prognosis is good.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

Objective To investigate the effect and underlying mechanism of roxadustat on apoptosis and senescence of renal tubular epithelial cell line HK-2 induced by heat stress.Methods After HK-2 cells were treated with different concentrations of roxadustat(10,20,30,40 and 50 μmol/L)for 24 h,CCK-8 assay was used to determine the optimal intervention concentration of roxadustat.HK-2 cells were divided into 4 groups(n=3):control group,roxadustat group(30 μmol/L,24 h),heat-stress group(43 ℃,2 h),and heat-stress+roxadustat group(30 μmol/L roxadustat treatmnet for 24 h followed by heat-stress 2 h).Cell viability was detected by CCK-8 assay.Expression of hypoxia-inducible factor-1α(HIF-1α),Cleaved Caspase-3,p16 and p21 at protein level was detected by Western blotting.Immunofluorescence assay was employed to observe the distribution of HIF-1α.β-galactosidase staining kit was utilized to detect SA-β-Gal activity.TUNEL staining was used to measure cell apoptosis.Results The highest cell viability was observed in the cells after 30 μmol/L roxadustat treatment.Heat stress resulted in a significant decrease in cell viability(P＜0.05),elevated protein levels of HIF-1α,Cleaved Caspase-3,p16 and p21(P＜0.05),enhanced SA-β-Gal activity(P＜0.05)and increased percentage of TUNEL-positive cells(P＜0.05)when compared with the cells in the control group.In comparison with the heat-stress group,the heat-stress+roxadustat group showed significant decrease in the protein levels of Cleaved Caspase-3,p16 and p21(P＜0.05),reduced activity of SA-β-Gal[(65.44±5.00)％vs(77.15±2.61)％,P＜0.05]and decreased percentage of TUNEL-positive cells[(16.73±2.20)％vs(46.40±13.87)％,P＜0.05],but increase in cell viability[(86.33±4.51)％vs(66.33±8.50)％,P＜0.05]as well as HIF-1α protein expression(P＜0.05).Furthermore,immunofluorescence assay showed that HIF-1α was mainly distributed in the nucleus and perinucleus.Conclusion Roxadustat attenuates heat stress-induced apoptosis and senescence of renal tubular epithelial cells by upregulating HIF-1α.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Objective:To observe the clinical characteristics and treatment prognosis of patients with ocular toxocariasis (OT).Methods:A retrospective clinical trial. From March 2018 to September 2021, 40 eyes of 40 OT patients diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. All patients underwent best corrected visual acuity (BCVA) and scanning laser ophthalmoscope (SLO) examination. Color Doppler ultrasound flow imaging (CDFI), fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were performed in 25, 26 and 26 eyes, respectively. Among the 40 patients, there were 23 males (57.5%, 23/40) and 17 females (42.5%, 17/40). All patients were monocular. Thirty patients (75.0%, 30/40) were younger than 18 years old, with the mean age of (9.60±0.60) years. Ten patients (25.0%, 10/40) were great than or equal to 18 years old, with the mean age of (34.60±4.52) years. Thirty-three patients (82.5%, 33/40) lived in rural areas for a long time. There were 27 patients (67.5%, 27/40) with a history of contact with dogs and cats. In 40 eyes, peripheral granuloma (peripheral type), posterior pole granuloma (posterior pole type), vitreous opacity similar to endophthalmitis (turbid type) and hybrid type were 18(45.0%, 18/40), 11(27.5%, 11/40), 6(15.0%, 6/40) ang 5(12.5%,5/40), respectively. All patients were treated with drugs and/or surgery after definite diagnosis. There were 28 eyes of peripheral type, posterior pole type and hybrid type, 17 eyes were treated with surgery and 11 eyes with drug treatment, respectively. Five eyes with turbid type were only treated with drugs. In 40 patients, 33 patients participated in follow-up. The follow-up time after treatment was (18.78±9.44) months. The improvement of BCVA was observed. The number of eyes with different BCVA before and after treatment was compared by χ2 test or Fisher's test. Results:At the first visit, the BCVA ranged from light perception to 0.6, including 20 eyes with BCVA <0.1, 13 eyes with BCVA 0.1-0.3, and 7 eyes with BCVA >0.3. The posterior vitreous anterior limiting membrane was thickened in 24 eyes (60.0%, 24/40). There were 27 eyes (67.5%, 27/40) with lamellar vitreous opacity and 22 eyes (55.0%, 22/40) with peripheral/posterior pole granulomas. Among 25 eyes examined by CDFI, 14 eyes (56.0%, 14/25) showed characteristic stratified or diffuse opacity in vitreous body. Of the 26 eyes examined by FFA, 15 eyes (57.7%, 15/26) had "fern-like" leakage of retinal capillaries, and the lesion had a patchy non-perfused area. In 26 eyes examined by OCT, epiretinal membrane, cystoid macular edema and vitreoretinal traction were 8 (30.8%, 8/26), 5 (19.2%, 5/26) and 2 (7.7%, 2/26) eyes, respectively. At the last follow-up, compared with before treatment, the BCVA of 5 eyes with turbid type increased, and the difference was statistically significant ( P<0.05). In 28 eyes with peripheral type, posterior pole type and hybrid type, 17 eyes with surgical treatment improved BCVA, and the difference was statistically significant ( χ2=6.258, P<0.05). In 11 eyes only treated with drugs, BCVA remained unchanged, and the difference was not statistically significant ( χ2=0.594, P>0.05). Conclusions:OT patients are mostly children; retinal granulomas, gray-white hyperplastic membrane behind lens or vitreous stratified opacity are specific characteristics. OT is mainly treated by glucocorticoid drugs and vitrectomy.

Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Humans ; Air Pollutants ; Sleep Apnea, Obstructive ; Polysomnography ; Sleep ; Pulmonary Disease, Chronic Obstructive