BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region （3’UTR） of slit guidance ligand 1 （Slit1） （Slit1-3’UTR） on the fibrotic phenotypes of cardiac fibroblasts （CFs） and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs （mCFs）. The expression of fibrosis-related genes in mCFs， such as collagen type 1 alpha1（COL1A1）， collagen type 3 alpha3 （COL3A1） and alpha smooth muscle actin （α-SMA） were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ （Ang Ⅱ） was used to treat mCFs， and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt， miR-34a-5p mimic was transfected into mCFs， followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt， and the levels of miR-34a-5p and its target gene SIRT1（si-SIRT1） in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes， proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs， while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes， and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap^-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ²=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ²=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ²=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ²=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.

Objective:To investigate the clinical characteristics, prognosis, and the impact of different secondary prevention strategies on stroke recurrence in patients with carotid web (CaW)-associated acute anterior circulation large vessel occlusion (LVO).Methods:A retrospective analysis was conducted on 401 patients with acute anterior circulation LVO who underwent mechanical thrombectomy at 2 advanced stroke centers, Xingtai Central Hospital and Xingtai People′s Hospital, from January 2018 to June 2024. CaW was identified using digital subtraction angiography (DSA) and other imaging modalities. Based on the presence of CaW, patients were divided into CaW group and non-CaW group. Differences between the 2 groups in baseline characteristics, clinical features, and clinical outcomes were compared, and long-term follow-up was conducted for the CaW group.Results:Among the 401 patients, the CaW group consisted of 16 patients (4.0%), while the non-CaW group included 385 patients (96.0%). Compared to the non-CaW group, patients in the CaW group were younger [53 (46, 58) years vs 65 (56, 76) years, Z=-3.811, P<0.001], had a higher proportion of M1 segment middle cerebral artery occlusion [13/16 vs 54.0% (208/385), χ2=4.602, P=0.032] and a lower proportion of internal carotid artery terminus occlusion [1/16 vs 40.0% (154/385), χ2=6.024, P=0.014]; the 90-day modified Rankin Scale (mRS) score was significantly lower in the CaW group [1.00 (0, 1.75) vs 3.00 (1.00, 4.00), Z=14.210, P<0.001], and the proportion of patients with favorable functional independence (mRS score 0-2) was significantly higher [15/16 vs 45.7% (176/385), χ2=12.350, P<0.001] in the CaW group; the incidence of pneumonia in the CaW group was significantly lower [2/16 vs 42.6% (164/385), χ2=4.562, P=0.033]. Among the 16 CaW patients, 10 received antiplatelet therapy, 4 underwent carotid artery stenting (CAS), and 2 underwent carotid endarterectomy (CEA). During a median follow-up of 29 months, patients who underwent CAS and CEA had no stroke recurrence, while 2 patients who received antiplatelet therapy had stroke recurrence and subsequently underwent CAS and CEA. Conclusions:The proportion of CaW among patients with acute anterior circulation LVO was 4.0%. The patients with CaW were younger and had a higher proportion of M1 segment middle cerebral artery occlusion. Following mechanical thrombectomy, patients in the CaW group had good functional outcomes. Simple drug therapy may be insufficient to prevent stroke recurrence in CaW patients, and CAS and CEA may be effective therapeutic options.

Objective:To analyze the incidence, clinical characteristics, and prognosis of basilar artery occlusion (BAO) patients presenting with paroxysmal sympathetic hyperactivity (PSH) as an initial symptom.Methods:A retrospective analysis was conducted on BAO patients with PSH manifestations who received endovascular treatment at Xingtai Central Hospital between January 2018 and August 2024. Demographic characteristics, clinical data, imaging findings, and follow-up information were collected.Results:A total of 136 BAO patients were included, of whom 22 cases (16.2%) were diagnosed with PSH. The age of the patients was (56.81±9.92) years, with males accounting for 86.4%(19/22). On admission, the Glasgow Coma Scale score was 4(3, 5), and the National Institutes of Health Stroke Scale score was 30(25, 35). The successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b-3) rate was 90.9%(20/22). In-hospital mortality was 50.0%(11/22), symptomatic hemorrhagic transformation occurred in 4.5% (1/22), and any type of intracranial hemorrhage occurred in 9.1%(2/22). Clinical features of PSH included tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging analysis showed a high proportion of cerebellar (100.0%, 22/22) and midbrain (72.7%, 16/22) involvement. The 90-day follow-up showed that 72.7%(16/22) of the patients had poor functional outcomes (modified Rankin Scale score of 4-6), and the 90-day mortality rate was 59.1%(13/22).Conclusions:Among patients with BAO undergoing endovascular therapy, the incidence of PSH as the initial manifestation was 16.2%(22/136). These patients were predominantly middle-aged men and commonly presented with tachycardia, tachypnea, hypertension, fever, diaphoresis, and increased muscle tone. Imaging findings mainly involved the cerebellum and midbrain. Despite a relatively high rate of recanalization, patients with PSH exhibited a higher risk of mortality and poor functional outcomes.

ObjectiveTo evaluate the efficacy and safety of acupoint application for post-stroke depression (PSD) by regulating gastrointestinal function. A secondary objective is to explore the potential mechanism underlying this approach from the perspective of gut microbiota.MethodsThis multicenter, randomized, double-blind (patients and assessors), placebo-controlled trial will enroll 80 patients with PSD, and include a 1-week run-in period, a 4-week treatment phase, and a 12-week follow-up. Eligible participants will randomly be assigned in a 1:1 ratio to either the acupoint application or placebo (non-acupoint) groups. Treatments will be administered thrice weekly for 4 weeks. The primary outcome is change in the Hamilton Rating Scale for Depression (HAMD) score. Secondary outcomes include the Beck Depression Inventory (BDI), 36-Item Short-Form Health Survey (SF-36), Barthel Index of Activities of Daily Living, Social Adaptation Self–Evaluation Scale (SASS), and gut microbiota profiling. All outcomes will be assessed at baseline (prior to treatment), during treatment (weeks 2 and 4), and during follow-up (weeks 8, 12, and 16). The Treatment Emergent Symptom Scale (TESS) will be used for evaluation throughout the 4-week treatment phase.DiscussionThe results of this study will provide important evidence supporting a novel treatment strategy for PSD that targets gastrointestinal regulation, potentially informing future clinical practice.