Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Objective To investigate the inhibitory effects of Wumeiwan on oxidative stress injury of ulcerative colitis mice induced by dextran sulfate sodium(DSS)by regulating Kelch-like ECH related protein 1(Keap-1)-nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathwayand.Methods Forty C57BL/6 mice were randomly divided into five groups:normal group,model group,positive control group,experimental-L,-H groups.UC mice model were induced by free access to 2％DSS water.Mice in normal and model group were orally administered with 0.9％NaCl,mice in positive control group were orally treated with Mesalazine solution(0.005 g·10 g-1·d-1),while mice in experimental groups were orally administered with Wumeiwan decoction at the dose of 0.13 and 0.26 g·10 g-1·d-1,respectively.All the drugs were administered for consecutive 7 days,1 times a day.The levels of disease activity index(DAI)and the colon length were scored.The levels of superoxide dismutase(SOD),catalase(CAT),cyclooxygenase-2(COX-2)and inducible nitric oxide synthase(iNOS)in colon tissue of mice were determined by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method.The level of Keap-1,Nrf2,HO-1 proteins in colon tissue were determined by Western blot method.Results The levels of DAI of seventh day in normal group,positive control group,experimental-L,-H groups were 0、(2.62±0.33),(1.87±0.35),(1.87±0.35)and(1.58±0.35);the colon lengths were(8.16±0.47)、(5.98±0.24),(7.58±0.38),(7.33±0.24)and(7.48±0.51)cm;the SOD mRNA were 1.01±0.16、0.40±0.01,1.43±0.45,0.65±0.01 and 0.83±0.02;the CAT mRNA were 1.01±0.20、0.45±0.01,0.84±0.02,0.68±0.07 and 0.87±0.05;the COX-2 mRNA were 1.03±0.33、16.65±0.60,4.78±0.25,14.07±0.60 and 7.39±0.15;the iNOS mRNA were 1.04±0.40、20.71±0.66,8.09±0.93,15.44±0.68 and 11.66±0.06;the levels of Keap-1 were 1.22±0.16、1.10±0.05,1.18±0.05,1.94±0.08 and 1.17±0.08;the levels of Nrf2 were 1.12±0.16、0.76±0.15,0.65±0.13,0.70±0.16 and 0.82±0.18;the levels of HO-1 were 1.34±0.15、1.00±0.12,0.89±0.10,1.50±0.18 and 1.40±0.13,respectively.Significant difference was found between normal group and model group(P＜0.01,P＜0.05);significant difference was also found between the experimental-L,-H groups and model group(P＜0.01,P＜0.05).Conclusion Wumeiwan can inhibit oxidative stress in mice with UC,the mechanisms may be related to adjusted the expression of Keap-1-Nrf2/HO-1 signaling pathway protein in colon.

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

OBJECTIVE: To explore clinical efficacy of platelet rich plasma (PRP) injection combined with extracorporeal shock wave therapy (ESWT) in treating osteochondral lesion of talus (OLT) with typeⅡa. METHODS: From January 2022 to June 2022, 45 patients with typeⅡa OLT were treated with PRP arthroscopic injection combined with ESWT, including 29 males and 16 females; aged from 18 to 63 years old with an average of(37.7±10.3) years old;the courses of disease ranged from 6 to 20 with an average of (13.3±4.8) months. American Foot and Ankle Association ankle and foot (AOFAS) score, visual analogue scale (VAS), cartilage injury volume and bone marrow edema volume were evaluated for ankle joint function and osteochondral recovery of talus before treatment, 3 and 6 months after treatment. RESULTS: All patients were followed for at least 6 months. No related complications occurred in all patients. AOFAS score were increased from(68.3±3.6) before treatment to (83.7±3.2) and (90.8±2.2) at 3 and 6 months after treatment, respectively (P<0.05). VAS decreased from (5.2±1.2) before treatment to (3.2±0.8) and (1.9±1.2) at 3 and 6 months after treatment (P<0.05). The injury volume of cartilage and subchondral bone decreased from (71.0±42.5) mm³ before treatment to (50.6±31.5) mm³ and (36.5±27.3) mm³ at 3 and 6 months after treatment (P<0.05). The bone marrow edema volume decreased from (1 182.7±675.1) mm³ before treatment to (656.1±455.1) mm³ and (382.1±485.6) mm³ at 3 and 6 months after treatment (P<0.05). CONCLUSION PRP intraarticular injection combined with ESWT for the treatment of typeⅡa OLT could alleviate clinical symptoms, effectively improve joint function, and promote cartilage repair and bone marrow edema absorption.
Humans ; Male ; Adult ; Female ; Talus/injuries* ; Platelet-Rich Plasma ; Middle Aged ; Extracorporeal Shockwave Therapy/methods* ; Adolescent ; Young Adult ; Injections, Intra-Articular

OBJECTIVE: To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism. METHODS: Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot. RESULTS: The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61. CONCLUSION Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
Animals ; Humans ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Imatinib Mesylate/pharmacology* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Signal Transduction

AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P<0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P<0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.