Objective To investigate whether curcumin(CUR)can reduce chondrocyte inflammation and cartilage degradation in osteo-arthritis(OA)and the underlying mechanisms.Methods A rat model of OA was established.Rats were randomly divided into a Sham,OA,CUR+OA,and deferoxamine(DFO)+OA groups with 10 mice in each group.Chondrocytes from 5-day-old SD rats were divided into the control,interleukin-1β(IL-1β),CUR+IL-1β,and DFO+IL-1β groups.A CCK-8 assay was performed to assess the effects of CUR on cell viability alone or combined with IL-1β.Toluidine blue staining and alcian blue staining were used to observe the morphological changes of IL-1β-induced chondrocytes.The expression of inflammatory response-related proteins(COX-2 and iNOS),extracellular matrix degradation-related proteins(COL2A and MMP13),and p53,SLC7A11,and GPX4 proteins during ferroptosis were detected by Western blotting.The mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial morphology was observed using transmission electron microscopy.Safranine O-fast green/HE staining was performed on cartilage tissues.Immunohistochemical staining was performed to detect COL2A and SLC7A11 expression levels.Results CUR and DFO were found to reduce IL-1β-induced inflammation,cartilage degradation,and ferroptosis,and restore mitochondrial function in chondrocytes.CUR also reversed IL-1β-induced changes in collagen Ⅱ,p53,SLC7A11,GPX4,MMP13,iNOS,and COX-2 levels.In vivo,intra-articular injection of CUR significantly improved cartilage injury in the OA rat model,and the percentages of COL2A-and SLC7A11-positive cells significantly increased in the CUR+OA and DFO+OA groups.Conclusion CUR inhibits ferroptosis and ameliorates cartilage degeneration in OA through p53 signaling pathway.

Objective To explore the effect of dexmedetomidine nasal spray(DNS)on perioperative sleep quality,anxiety stress in patients undergoing hysterectomy.Methods A total of 75 patients who underwent laparoscopic hysterectomy at Taizhou First People's Hospital from May to December 2024 were selected and divided into control group(37 cases)and experimental group(38 cases)according to the random number table method.Patients in experimental group were respectively sprayed with 50μg or 75pg of DNS at 20:30 on the night before surgery and the night after surgery,patients in control group were respectively given an equal volume of normal saline nasal spray at 20:30 on the night before surgery and the night after surgery.Athens insomnia scale(AIS)scores and sleep quality on the first night of admission(T0),the first night before surgery(T1),the first night after surgery(T2),and the second night after surgery(T3),the scores of hospital anxiety and depression scale(HADS),salivary cortisol andα-amylase on the first day of admission,before entering the operating room,and on the first and second days after surgery,and incidence of adverse reactions 60 minutes after administration between two groups of patients were observed and compared.Results Compared with control group,the AIS scores in experimental group at T1,T2 and T3 were significantly lower,the latency to sleep was significantly shortened,the total sleep time and non-rapid eye movement sleep time were significantly prolonged,and rapid eye movement sleep time was significantly shortened(P＜0.05),number of awakenings at T1 and T2 decreased significantly(P＜0.05),and HADS score,salivary cortisol and α-amylase levels before entering the operating room,and on the first and second days after surgery were all significantly decreased(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions within 60 minutes after administration between two groups of patients(P＞0.05).Conclusion Perioperative administration of DNS can significantly improve the sleep quality of patients undergoing laparoscopic hysterectomy,relieve anxiety,reduce stress levels,and has high safety.

Objective To investigate whether curcumin(CUR)can reduce chondrocyte inflammation and cartilage degradation in osteo-arthritis(OA)and the underlying mechanisms.Methods A rat model of OA was established.Rats were randomly divided into a Sham,OA,CUR+OA,and deferoxamine(DFO)+OA groups with 10 mice in each group.Chondrocytes from 5-day-old SD rats were divided into the control,interleukin-1β(IL-1β),CUR+IL-1β,and DFO+IL-1β groups.A CCK-8 assay was performed to assess the effects of CUR on cell viability alone or combined with IL-1β.Toluidine blue staining and alcian blue staining were used to observe the morphological changes of IL-1β-induced chondrocytes.The expression of inflammatory response-related proteins(COX-2 and iNOS),extracellular matrix degradation-related proteins(COL2A and MMP13),and p53,SLC7A11,and GPX4 proteins during ferroptosis were detected by Western blotting.The mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial morphology was observed using transmission electron microscopy.Safranine O-fast green/HE staining was performed on cartilage tissues.Immunohistochemical staining was performed to detect COL2A and SLC7A11 expression levels.Results CUR and DFO were found to reduce IL-1β-induced inflammation,cartilage degradation,and ferroptosis,and restore mitochondrial function in chondrocytes.CUR also reversed IL-1β-induced changes in collagen Ⅱ,p53,SLC7A11,GPX4,MMP13,iNOS,and COX-2 levels.In vivo,intra-articular injection of CUR significantly improved cartilage injury in the OA rat model,and the percentages of COL2A-and SLC7A11-positive cells significantly increased in the CUR+OA and DFO+OA groups.Conclusion CUR inhibits ferroptosis and ameliorates cartilage degeneration in OA through p53 signaling pathway.

Objective To explore the effect of dexmedetomidine nasal spray(DNS)on perioperative sleep quality,anxiety stress in patients undergoing hysterectomy.Methods A total of 75 patients who underwent laparoscopic hysterectomy at Taizhou First People's Hospital from May to December 2024 were selected and divided into control group(37 cases)and experimental group(38 cases)according to the random number table method.Patients in experimental group were respectively sprayed with 50μg or 75pg of DNS at 20:30 on the night before surgery and the night after surgery,patients in control group were respectively given an equal volume of normal saline nasal spray at 20:30 on the night before surgery and the night after surgery.Athens insomnia scale(AIS)scores and sleep quality on the first night of admission(T0),the first night before surgery(T1),the first night after surgery(T2),and the second night after surgery(T3),the scores of hospital anxiety and depression scale(HADS),salivary cortisol andα-amylase on the first day of admission,before entering the operating room,and on the first and second days after surgery,and incidence of adverse reactions 60 minutes after administration between two groups of patients were observed and compared.Results Compared with control group,the AIS scores in experimental group at T1,T2 and T3 were significantly lower,the latency to sleep was significantly shortened,the total sleep time and non-rapid eye movement sleep time were significantly prolonged,and rapid eye movement sleep time was significantly shortened(P＜0.05),number of awakenings at T1 and T2 decreased significantly(P＜0.05),and HADS score,salivary cortisol and α-amylase levels before entering the operating room,and on the first and second days after surgery were all significantly decreased(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions within 60 minutes after administration between two groups of patients(P＞0.05).Conclusion Perioperative administration of DNS can significantly improve the sleep quality of patients undergoing laparoscopic hysterectomy,relieve anxiety,reduce stress levels,and has high safety.

ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai， so as to understand their health status and explore the influencing factors of birth defects. MethodsBased on the birth registration covering the entire city of Shanghai， the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group， and healthy children were matched as the control group. Basic information， health status， maternal pregnancy history， and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis. ResultsA total of 18 875 infants born between January 1， 2011， and December 31， 2021， were included， among which 11 500 （60.93%） were children with severe birth defects and 7 375 （39.07%） were healthy children. The logistic regression model analysis showed that being male （OR=1.20， 95%CI：1.13‒1.29）， non-Shanghai residency （OR=1.16， 95%CI： 1.06‒1.25）， multiple births （OR=8.41， 95%CI：6.25‒11.30）， artificial insemination （OR=2.31， 95%CI：1.34‒3.99）， in vitro fertilization （IVF） （OR=1.85， 95%CI：1.44‒2.38）， maternal exposure to radiation （OR=1.83， 95%CI：1.07‒3.14）， maternal illness during pregnancy （OR=1.61， 95%CI：1.49‒1.74）， experiencing a traumatic event during pregnancy （OR=2.34， 95%CI：1.88‒2.92）， paternal chemical exposure （OR=1.88， 95%CI：1.32‒2.69）， paternal radiation exposure （OR=1.65， 95%CI： 1.18‒2.33）， family history of birth defects （OR=8.18， 95%CI： 3.96‒16.89）， being overweight before pregnancy （OR=1.16， 95%CI： 1.07‒1.27）， being obese before pregnancy （OR=1.15， 95%CI：1.03‒1.30）， and being excessively obese before pregnancy （OR=1.52， 95%CI：1.26‒1.83） were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis （OR=27.87， 95%CI： 20.84‒37.27）， especially ranking first in cardiac malformations. ConclusionAfter controlling for influencing factors， maternal overweight， obesity， and excessive obesity before pregnancy， artificial insemination， and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle， improving physical and mental health during pregnancy， and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.

Objective:To explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) combined with blood glucose at admission for a positive blood culture for sepsis.Methods:A single-center retrospective cohort study was conducted. According to the 2016 American Society of Critical Care/European Society of Critical Care Medicine (SCCM/ESICM) and diagnostic criteria for sepsis and septic shock-3.0 (sepsis-3.0), patients with sepsis were admitted to the Emergency Department of Fujian Medical University Union Hospital for more than 24 h from January 2019 to December 2021 were enrolled. Age, gender, sequential organ failure assessment, source of infection, NLR, and blood culture results were recorded. Based on the blood culture results, patients were divided into a blood culture positive group (Gram-positive group, Gram-negative group) and blood culture negative group, and the differences between the groups were compared. The risk factors for a positive blood culture were analyzed using multivariate logistic regression. A receiver operating characteristic analysis was performed for the NLR combined with the blood glucose measurement.Results:A total of 265 patients with sepsis were included, of which 62 were positive in blood culture (15 Gram-positive patients, 37 Gram-negative patients and 10 fungal patients). The positive rate of blood culture was 23.4%. The number of patients with history of diabetes, neutrophil count, procalcitonin, blood glucose, and NLR in the positive blood culture group were significantly higher than those in the negative blood culture group (all P<0.001). Multivariate logistic regression analysis revealed that random admission blood glucose ( OR=1.116, 95% CI: 1.051~1.186, P<0.001) and NLR ( OR=1.039, 95% CI: 1.015~1.064, P=0.001) were independent risk factors for blood culture positivity in sepsis patients. For patients with blood culture positive, and with Gram-negative bacterial bloodstream infections, the AUC of the NLR combined with the admission blood glucose level was 0.819 (95% CI: 0.761-0.877, P<0.001) and 0.871 (95% CI: 0.813-0.928, P<0.001), respectively. Conclusions:The combination of NLR and random admission blood glucose could provide a good predictive value for blood culture positive and gram-negative bacterial bloodstream infections in sepsis patients.

Objective:To analyze the clinical features, prognosis and risk factors of SARS-CoV-2 associated acute pancreatitis (SAAP), and provide a basis for early prevention and treatment of SAAP.Methods:Patients with coronavirus disease 19 infection (COVID-19) admitted to Zhejiang Provincial People's Hospital from December 1, 2022 to January 31, 2023 were retrospectively analyzed. Clinical characteristics such as age, gender and other data were recorded, and the indexes of blood routine, liver and kidney function, inflammatory factor, coagulation function, blood gas analysis, immunoglobulin and complement were collected after admission. Patients were divided into pancreatic injury group and non-pancreatic injury group according to the level of serum amylase/lipase. The difference of prognosis and related hematological parameters between the two groups was compared. Multifactorial logistic regression equation was constructed to analyze the risk factors of SAAP.Results:A total of 2 101 patients with COVID-19 who met the criteria were included, including 298 patients in the pancreatic injury group and 1 803 patients in the non-pancreatic injury group. 17 cases (5.7%) in the pancreatic injury group met the diagnostic criteria for AP. The age, male percentage and mortality rate of the pancreatic injury group were all significantly higher than those of the non-pancreatic injury group (all P<0.05). In the pancreatic injury group, white blood cell count, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), calcitoninogen, erythrocyte sedimentation rate, inflammatory cytokines, tumour necrosis factor, liver and kidney functions, coagulation (D-dimer and plasma fibrinogen degradation products), and lactate level were significantly higher than those in the non-pancreatic injury group (all P<0.05). Serum complement C3, albumin, albumin globule ratio and arterial oxygenation index were lower in the pancreatic injury group (all P<0.05). Multifactorial logistic regression analysis showed that gender, age, CRP, calcitoninogen, total bilirubin, creatinine, PaO 2, PaO 2/FiO 2 and lactate were independent risk factors for the occurrence of pancreatic injury in patients with COVID-19 (all P<0.05). Conclusions:Inflammation-related markers, D-dimer and fibrinogen degradation products were significantly higher in COVID-19 patients comorbid with pancreatic injury than in the patients without pancreatic injury. The risk of SAAP was significantly higher in male patients of senior age. Sex, age, CRP, calcitoninogen, total bilirubin, creatinine, oxygenation index, and lactic acid were independent risk factors for the onset of pancreatic injury in COVID-19 patients.

Objective:To observe and analyze the clinical and imaging features of eyes with cystoid macular degeneration (CMD) secondary to chronic central serous chorioretinopathy (cCSC).Methods:A retrospective clinical study. From February 2018 to June 2023, 9 patients of 15 eyes with cCSC secondary CMD diagnosed by ophthalmology examination in Yunnan University Affiliated Hospital were included in the study. All patients were male. The age was (53.67±3.83) years. The cases of binocular and monocular were 6 and 3 respectively. The visual acuity of the affected eye ranges from 0.02 to 0.1, which cannot be corrected. Visual acuity decreased and the duration of shadow occlusion was >1 year. Half dose photodynamic therapy (PDT) was performed on 8 eyes. All the patients underwent the best corrected visual acuity, posterior mydriatic fundus color photography, infrared fundus photography (IR), fundus autofluorescence (AF), fluorescein fundus angiography (FFA), optical coherence tomography (OCT), and multi-wavelength dazzling imaging (MC). The patients who received half dose PDT were followed up until 3 months after treatment. Patients who did not receive treatment were followed up to 2 years after the first diagnosis.Results:The light reflection in macular area decreased or disappeared in all eyes, and abnormal macular pigmentation was observed in 12 eyes. IR examination showed diffuse patchy weak fluorescence in the macular area in all affected eyes, and dotted strong fluorescence in the periphery. Fundus AF examination showed disc-like weak AF in the macular area, and scattered small amounts of strong AF in the middle and margins, among which the retinal pigment epithelium (RPE) atrophy trace in the macular area was observed in 7 eyes. By MC examination, the green signal in the macular area of the posterior pole of all affected eyes was uneven and mottled. FFA examination showed that no abnormal fluorescein leakage was observed in 15 eyes and 8 eyes showed strong fluorescence caused by diffuse permeation fluorescence. A small amount of active fluorescein was found in 7 eyes. OCT examination showed that there were several cystic cavities of different sizes in all the affected eyes, RPE atrophied to different degrees, and RPE cell compensatory ridges and tubular structures in the outer retina were seen in 6 eyes; 7 eyes with CMD and active leakage showed signs of subcortical fluid accumulation. Choroidal hypertrophy was seen in all affected eyes, with significant expansion of the great vascular layer and compression of the middle vascular layer and capillary layer. In 8 eyes treated with half-dose PDT, 6 eyes were ineffective at 3 months after treatment. The treatment was effective in 2 eyes. In 7 eyes that did not receive half-dose PDT, CMD structure did not improve significantly after 2 years of follow-up. The visual acuity decreased with the prolongation of the disease.Conclusions:CMD is more common in cCSC with a long course of disease, which has significant effects on vision and poor prognosis. Fundus color photography shows that the reflection in the macular area of the pole is weakened or disappeared, which may be combined with macular abnormal pigmentation. IR and AF examination show uneven fluorescence in macular area. The green signal in macular area is not uniform according to MC inspection. FFA shows strong fluorescence caused by diffuse permeable fluorescence and fluorescein leakage in active lesions. OCT examination shows that multiple small sacs or connections between sacs were broken and fused, and RPE atrophied to varying degrees.

Objective:To explore the molecular mechanism of pathological changes in osteoarthritis (OA) through applying bioinformatics to analyze the miRNA-mRNA regulatory network.Methods:MiRNA expression data from human serum samples were downloaded from the Gene Expression Omnibus database. Differentially-expressed miRNA was identified using the linear modelling package of the Bioconductor software suite. The target differentially-expressed mRNA was predicted using version 2.0 of the miRWalk database. Version 3.7.1 of the Cytoscape software was used to construct the miRNA-mRNA regulatory network for OA. The target genes were analyzed by using gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The protein-protein interaction network was constructed and the core genes in osteoarthritis pathology were screened out.Results:A total of 7 differentially-expressed miRNAs (all down-regulated) and 900 mRNAs were identified, mostly involved in the negative regulation of protein binding, DNA binding, or transcription in the cell cycle. Ten core genes were screened out: MAPK1, TP53, MAPK14, CCND1, EP300, POLR2E, POLR2F, ABL1, RAC1 and SKIV2L2.Conclusions:Multiple miRNAs, target genes and signaling pathways are involved in the development of OA. The miRNA-mRNA regulatory network identified provides new ideas for exploring the molecular mechanism of OA′s pathology and its clinical diagnosis and treatment.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.