AIM: To explore the clinical efficacy of 25G minimally invasive vitrectomy combined with 41G ultra-micro subretinal injection of tissue plasminogen activator(t-PA)in the treatment of subretinal hemorrhage(SMH).METHODS: Retrospective study. A totally 60 patients(60 eyes)who visited the Ophthalmology Department of Yuebei People's Hospital from June 2022 to September 2024 and were diagnosed with submacular hemorrhage were selected. According to different treatment methods, they were divided into a control group of 30 eyes(25G vitrectomy combined with intravitreal injection of t-PA)and an observation group of 30 eyes(25G vitrectomy combined with 41G subretinal injection of t-PA). The complete clearance rate of macular hemorrhage, best corrected visual acuity(BCVA), changes in intraocular pressure, central retinal thickness(CRT), the occurrence of postoperative complications were observed in the two groups of patients.RESULTS:The two groups of general data are comparable. After treatment for 7 d, the rate of complete clearance of macular hemorrhage was higher in the observation group than in the control group(100% vs 80%, P<0.05). There was no significant difference between the two groups in the comparison of BCVA at 1 d and 6 mo postoperatively(all P>0.05), and in the comparison of BCVA between the two groups at 7 d, 1, and 3 mo postoperatively, BCVA of the observation group was better than that of the control group(all P<0.05); and the intraocular pressure of the observation group was lower than that of the control group at 1 d, 7 d, and 1 mo postoperatively(all P<0.05), and there was no significant difference between the two groups in the comparison of intraocular pressure at 3 and 6 mo postoperatively(all P>0.05). There was no significant difference between the two groups in the comparison of CRT at 1 d and 6 mo postoperatively(all P>0.05), and CRT was lower than that of the control group at 7 d, 1 and 3 mo postoperatively(all P<0.05). The total incidence of complications in the observation group was not statistically different from that in the control group(0 vs 10%, P>0.05).CONCLUSION: The 25G minimally invasive vitrectomy combined with 41G ultra-microsubretinal injection of t-PA is more efficient in removing subretinal hemorrhage, promotes early anatomical restoration, and has a comparable long-term visual prognosis to the conventional method, with a favorable safety profile.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

ObjectiveTo investigate the application of endoscopy in obtaining the great saphenous vein （GSV） during coronary artery bypass grafting （CABG） and explore the learning curve， with a particular focus on common challenges encountered during the learning process and their impact on early clinical outcomes. MethodsA retrospective analysis was conducted on clinical data from 83 patients who underwent off-pump CABG with endoscopic GSV harvesting at the First Affiliated Hospital of Zhengzhou University from July 2013 to April 2014. Patients were categorized into four groups based on the chronological order of their hospitalization： Group A （novice group， n=20）， Group B （proficient group， n=20）， Group C （progressive group， n=20）， and Group D （mature group， n=23）. Differences in perioperative and midterm follow-up outcomes among the groups were analyzed to determine the learning curve period. ResultsThe study population had a mean age of （60.22±8.06） years and a mean body weight of （69.77±11.66） kg. Comorbidities included hypertension （24 cases）， diabetes （26 cases）， and subacute cerebral infarction （14 cases）. The novice group exhibited significantly shorter GSV length-to-harvest time ratio relative to the other three groups （P<0.001） and a significantly higher incidence of main vein damage （P=0.006）. However， there was no statistically significant difference in graft patency at the 1-year follow-up. ConclusionThorough and reliable technical training in endoscopic GSV harvesting is essential to minimize vascular injury caused by novice operators. Approximately 20 cases of hands-on experience and a careful self-analysis of procedural challenges are likely required to achieve proficiency in GSV harvesting.

BACKGROUND:The proximal femoral nail antirotation is the preferred treatment for reverse osteoporotic intertrochanteric fractures.Bone cement enhancement can reduce the probability of proximal femoral nail antirotation cut-out and cut-through,but there are no relevant biomechanical studies demonstrating the effect of bone cement content and location on the stress and displacement of the fracture end. OBJECTIVE:To investigate the effects of different contents and locations of bone cement in cement-reinforced proximal femoral nail antirotation on stress,strain,and displacement of reverse osteoporotic femoral intertrochanteric fractures in the elderly by finite element analysis. METHODS:A healthy adult female right femur model was extracted by Mimics software and smoothed in Geometric software.Five types of internal fixation methods of proximal femoral nail antirotation(cementless,cephalic spherical 1 mL,cephalic spherical 2 mL,cephalic spherical 3.4 mL,and cylindrical 5 mL around spiral blade)and femoral intertrochanteric fracture(AO subtype 31-A3.1 type)model were established in Solidworks software.After assembly,the total stress distribution,peak stress and displacement of the five models of implants with the femur were compared in Ansys software. RESULTS AND CONCLUSION:(1)The peak stresses of proximal femoral nail antirotation with head-end spherical 1 mL,head-end spherical 2 mL,head-end spherical 3.4 mL,and cylindrical 5 mL enhanced proximal femoral nail antirotation around the spiral blade respectively were 571.07 MPa(located at the junction of the spiral blade and the main nail),495.45 MPa(located at the junction of the spiral blade and the main nail),467.20 MPa(located at the junction of the main nail and the distal screw connection),642.70 MPa(located at the junction of the main nail and distal screw connection),and 458.58 MPa(located at the junction of the spiral blade and the main nail).(2)The maximum displacements of proximal femoral nail antirotation with head end sphere 1 mL,head end sphere 2 mL,head end sphere 3.4 mL,and with cylindrical 5 mL enhancement around the spiral blade were 9.260 5,7.589 1,7.316 8,6.790 7,and 6.615 7 mm,respectively,all of which were located at the proximal end of the femoral head.(3)These findings revealed that for reverse femoral intertrochanteric fractures treated with proximal femoral nail antirotation,the bone cement enhancement had significant mechanical stability compared with no enhancement,and the enhancement of the spiral blade 5 mL around the perimeter was the best,which is more preferable for aged unstable intertrochanteric fractures.

BACKGROUND:Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty.Many studies suggest that the inflammasome may play an important role during the osteolysis.Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including anti-inflammatory,anti-oxidation,and antitumor,but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE:To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS:(1)In vivo test:Fifteen C57BL/6 mice were randomly divided into sham operation group,osteolysis group and melatonin group by random number table method,with 5 mice in each group.The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromium-molybdenum(CoCrMo)particles into the sagittal suture of the skull.After injection,the melatonin group was intraperitoneally injected with 50 mg/(kg·d)of melatonin for 14 consecutive days.After drug intervention,the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture.(2)In vitro test:Mouse bone marrow-derived macrophages and THP-1 cells(which had been induced to differentiate into macrophages)were taken and divided into seven groups:normal group,lipopolysaccharide group,lipopolysaccharide+CoCrMo group and melatonin 0.5,1,1.5,2 mmol/L groups(lipopolysaccharide and CoCrMo were added to the melatonin intervention groups).After the intervention for 6 hours,the expression of related proteins(NLRP3,Caspase-1,interleukin-1β,and gasdermin D,gasdermin D-N terminal)in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay.Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION:(1)In vivo test:Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced,and the bone tissue structure was severely damaged.Compared with the osteolysis group,the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased,and the destruction of tissue structure was reduced.(2)In vitro test:For mouse bone marrow-derived macrophages,lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate,and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner.CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture,while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner.For THP-1 cells,the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles,and the expression of these proteins was decreased dose-dependent by melatonin intervention.Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture,and melatonin intervention could reduce the release of lactate dehydrogenase and cell death.(3)The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis.

Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

In order to understand the prevalence and antimicrobial resistance of Enterococcus faeca-lis(E.faecalis)and Enterococcus faecium(E.faecium)isolated from human,pig and environ-ment in a Xinjiang pig farm,and to investigate the prevalence and potential harm of antimicrobial resistance genes,858 fecal samples from pig farm workers,anal swabs from pig and environment were collected for isolation,identification,antimicrobial susceptibility test and drug resistance gene detection.The results showed that 429 strains of E.faecalis and 222 strains of E.faecium were i-solated.The distribution of Enterococcus species varied among different sources.The isolation rate of E.faecalis was higher in pig anal swabs(73.1％,309/423)and human fecal samples(68.4％,26/38).E.faecium(42.3％,168/397)was mainly isolated from environmental samples.The drug resistance of E.faecalis and E.faecium isolated from pigs was similar to that of E.faecium isola-ted from environment.The drug resistance rates of E.faecalis and E.faecium isolated from pigs were more serious than those from humans to tetracycline,doxycycline,florfenicol and erythromy-cin,and they were more sensitive to ciprofloxacin and levofloxacin.More than 30.0％of E.faecalis and E.faecium isolated from pigs and environment were intermediate to linezolid.E.faecalis from three sources and E.faecium from environmental sources were mainly resistant to five drugs,while E.faecium from pigs was mainly resistant to six drugs.The detection rates of tet(M)and tet(L)genes in E.faecalis and E.faecium isolates from human,animal and environmental sources were more than 70.0％,which was consistent with the results of drug sensitivity.In addition,the cfr,optrA and poxtA genes that mediate oxazolidinone resistance were detected to varying extent.The cfr gene was only detected in four E.faecalis isolates from swine,one E.faecalis isolate from environment and two E.faecium isolates from environment.The positive rate of optrA gene in E.faecium isolated from pigs and environment was higher than that from humans,and the posi-tive rate was more than 60.0％.The positive rate of poxtA gene in E.faecium isolated from pigs and humans was more than 45.0％.The similar drug resistance situation suggests that there is the phenomenon of mutual contamination of drug-resistant bacteria in human-animal-environment.Therefore,we should consider from the perspective of one health,formulate comprehensive disin-fection and control programs,block the transmission route of drug-resistant strains and drug re-sistance genes between human-animal-environment,standardize the use of antibiotics,and reduce the enrichment of antibiotics in human-animal-environment,so as to reduce the risk of drug-resist-ant bacteria.

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenviron-ment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.