BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer,analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers.Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications.Based on the distribution characteristics of H3K27ac,the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored.The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues.Compared with normal gastric mucosa,the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer.A total of 8847 enhancers with increased activity in intestinal type gastric cancer were identified,accounting for 8.3%of all enhancers,which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells.A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers,which was able to predict the overall survival of patients.Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer.These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC,E2F3 and other genes.A prognosis model based on enhancer target genes is constructed.

Objective:To investigate the application value of cannulated screws in the treatment of Hauck type Ⅱ ulnar styloid process fracture.Methods:The clinical data of 93 patients with Hauck type Ⅱ ulnar styloid process fracture who received treatment at Fuzhou Second Hospital Affiliated to Xiamen University from December 2020 to February 2023 were retrospectively analyzed for a case-control study. Among these patients, 38 patients did not undergo surgical fixation and 55 patients underwent surgical fixation. Twenty-seven patients underwent surgical fixation with cannulated screws and twenty-eight patients underwent surgical fixation with Kirschner wires. The fracture healing, postoperative rehabilitation, and functional recovery of the wrist were compared among groups.Results:The fracture healing rate and the incidence of distal radioulnar joint instability in the surgical fixation group were 100.00% (55/55) and 5.45% (3/55), respectively. These were significantly higher and lower respectively compared with the non-surgical fixation group [57.89% (22/38), 50.00% (19/38), χ 2 = 27.66, 24.69, both P < 0.001]. The wrist function recovery in the surgical fixation group was significantly superior to that in the non-surgical fixation group ( Z = -5.18， P < 0.001). There were no statistically significant differences in operative time and intraoperative blood loss between the cannulated screw group and the Kirschner wire group [(21.41 ± 5.15) minutes vs. (20.93 ± 5.71) minutes, (2.11 ± 0.97) mL vs. (2.07 ± 0.90) mL, t = 0.32, 0.15, both P > 0.05]. The fracture healing time and rehabilitation intervention time in the cannulated screw group were shorter than those in the Kirschner wire group [(6.48 ± 1.05) weeks vs. (9.14 ± 1.24) weeks, (2.11 ± 0.32) weeks vs. (3.11 ± 0.57) weeks, t = 8.57, 7.98, both P < 0.001]. The postoperative wrist function scores in the cannulated screw group were superior to those in the Kirschner wire group ( Z = -2.21, P < 0.05). Conclusion:For patients with Hauck type Ⅱ ulnar styloid process fracture, surgical fixation can promote the recovery of wrist function after surgery, and cannulated screw fixation is an effective method for the treatment of Hauck type Ⅱ ulnar styloid process fracture.

Objective:To construct a physical restraint reduction scheme based on eCASH concept (that is early Comfort using Analgesia, minimal Sedatives and maximal Human care for adult patients after cardiac surgery, and intervene, and to evaluate its effectiveness.Methods:A non-synchronous case-control study was conducted. A total of 486 patients after cardiac surgery admitted to the cardiac surgery intensive care Unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong First Medical University from July to October 2022 were enrolled as subjects. According to the implementation time node of the physical restraint reduction scheme, 250 patients admitted from July to August were served as the control group, and 236 patients admitted from September to October were served as the observation group. The control group adopted the routine physical restraint nursing process, including selecting the appropriate restraint device according to the patient's condition and consciousness and following the doctor's advice, and checking on time to prevent adverse reactions. The observation group implemented the physical restraint reduction scheme based on eCASH concept, including preoperative visit, postoperative assessment of whether patients needed physical restraint according to the restraint decision wheel and the physical restraint flow, and adopted personalized nursing programs. The restraint rate, restraint duration, incidence of restraint-related complication (edema of the limbs, redness and swelling of the skin in the restricted area, skin rupture, etc.), restraint device application standard rate, delirium rate and incidence of unplanned extubation event were compared between the two groups.Results:There was no significant difference in age, gender, cardiopulmonary bypass, endotracheal catheter retention duration and operation type between the two groups with comparability. The restraint rate in the observation group was significantly lower than that in the control group [16.95% (40/236) vs. 84.40% (211/250), P < 0.01], and the restraint duration was significantly shorter than that in the control group [hours: 0 (0, 1.0) vs. 7.0 (5.5, 10.0), P < 0.01], the incidence of restraint-related complication and delirium were significantly lower than those in the control group [restraint-related complication: 0.85% (2/236) vs. 1.60% (4/250), delirium: 0% (0/236) vs. 2.80% (7/250), both P < 0.05], and the restraint device application standard rate was significantly higher than that in the control group [100.00% (40/40) vs. 90.52% (191/211), P < 0.05]. No unplanned extubation event occurred in both groups. Conclusion:The physical restraint reduction scheme based on eCASH concept in adult patients after cardiac surgery can effectively reduce the restraint rate and the incidence of restraint-related complication, shorten the restraint duration, reduce the incidence of delirium, improve the standardization of restraint device application, without increasing the incidence of unplanned extubation events.

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

Objective To investigate the value of quantitative parameters(Kep and Ktrans)of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),in predicting perineural invasion(PNI)in peripheral prostate cancer(PCa).Methods The clinical and preoperative MRI data of 45 patients with peripheral PCa who underwent radical prostatectomy(RP)were analyzed retrospectively.According to the pathological results,the patients were divided into PNI group(n=27)and non-PNI group(n=18).Various parameters,including age,total prostate specific antigen(tPSA),Ktrans value,Kep value,apparent diffusion coefficient(ADC)value,prostate volume,maximum lesion diameter,and prostate-specific antigen density(PSAD)were compared between the two groups.Multivariate logistic regression analysis was used to identify independent predictors of PNI,and a joint prediction model was established.The DeLong test was used to compare differences in the area under the curve(AUC)between the joint prediction model and each independent predictor.Results The univariate analysis identified statistically significant differences in the tPSA,Ktrans value,ADC value,maximum lesion diameter,and PSAD between the two groups(P＜0.01).The multivariate analysis showed that the Ktrans value and the maximum lesion diameter were independent predictors of PNI,with AUC of 0.854 and 0.874,respectively(P＜0.01).The AUC of the joint prediction model for PNI diagnosis was 0.955(P＜0.001).The DeLong test showed that the AUC of the joint prediction model for PNI diagnosis was better than that of the Ktrans and the maximum lesion diameter(P＜0.05).Conclusion The Ktrans value can be used to predict PNI.Furthermore,the combination of the Ktrans value and the maximum lesion diameter is more effective for predicting PNI than traditional methods.This provides more reference basis for the selection of clinical treatment methods.

Objective To investigate the value of a nomogram model constructed from intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics in predicting the status of lymphovascular space invasion(LVSI)in cervical cancer.Methods A retrospective analysis was conducted on 178 cervical cancer patients confirmed by postoperative pathology,with 70 cases of LVSI(+)and 108 cases of LVSI(-).The patients were divided into a training set[142 cases,including 54 cases of LVSI(+)and 88 cases of LVSI(-)]and a test set[36 cases,including 16 cases of LVSI(+)and 20 cases of LVSI(-)]at a ratio of 8:2.All underwent magnetic resonance imaging before surgery,and regions of interest were manually delineated layer by layer on the T2WI sequence,with the peritumoral region being uniformly expanded outward.Univariate logistic analysis was performed on clinical factors to select independent factors for cervical cancer LVSI(+).Radiomic features were extracted separately from the intratumoral region,the peritumoral region,and the intratumoral-peritumoral region to construct radiomics models,and the differences between the peritumoral and the intratumoral-peritumoral models were compared.A combined model was established based on the radiomics scores of the optimal intratumoral-peritumoral model and clinical independent predictive factors,and a nomogram was plotted.Receiver operating characteristic curves were used to evaluate the diagnostic performance of each model,and decision curve analysis was used to assess the clinical value of the models.Results The combined model demonstrated the best performance among the various models,with AUC of 0.970 in the training set and 0.803 in the test set.Conclusion Intratumoral and peritumoral magnetic resonance imaging radiomics combined with clinical characteristics can effectively predict LVSI in cervical cancer.

Objective To explore the feasibility and diagnostic value of ultra-fast scanning scheme based on deep learning-based reconstruction(DLR)for cervical MR examination.Methods Thirty-six subjects were prospectively enrolled and underwent both conventional scheme(scan time:6 min 14 s)and ultra-fast scheme(2 min)cervical spine MR scanning to acquire encompassing sagittal T1WI,sagittal adipose suppression T2WI and axial T2WI.The ultra-fast MRI were reconstructed using DLR method.The subjective and objective evaluations on imaging qualities of different MRIs were compared,along with the inter-observer agreement for diagnosing intervertebral disc degeneration and herniation.Results Compared with conventional MRI,artifacts in ultra-fast DLR images significantly reduced(P＜0.05).The subjective evaluation results of MRI had good agreement(all Kappa≥0.60).Compared with conventional MRI,the sagittal T1WI,T2WI and axial T2WI obtained with ultra-fast DLR showed significantly improved signal-to-noise ratio(SNR)of the spinal cord,cerebrospinal fluid(CSF)and vertebral body,as well as the spinal cord/CSF contrast(all P＜0.001).The Kappa value of 2 physicians for diagnosing intervertebral disc degeneration based on ultra-fast DLR and conventional scheme images was 0.94 and 1.00,respectively,of intervertebral disc herniation was 0.96 and 0.98,respectively.Conclusion Compared with conventional scanning scheme,using ultra-fast DLR scheme in cervical MR examination could shorten scanning time while achieve similar image quality and diagnostic accuracy.

A virus was successfully isolated from a sick cat exhibiting clinical signs such as oral mu-cosal ulceration,nasal mucosal redness,and increased nasal secretions utilizing F81 cells.Through a comprehensive analysis as such PCR amplication,sequencing,morphology,serology,and animal re-gression tests,the virus was identified as a feline calicivirus and named FCV-BJ,an inactivated vac-cine was developed from this isolated strain its safety and efficacy were assessed.The results re-vealed that the isolated FCV-BJ strain exhibited characteristic serological and morphological fea-tures consistent with caliciviruses.Furthermore,inoculation of cats with the FCV-BJ demonstrated the strain is highly virulent and the cats manifested the clinical signs of feline calicivirus infection.For the vaccination trial,domestic cats were immunized with inactivated fifth-generation virus cell culture at varying dilutions,followed by a booster immunization after 21 days.Fourteen days after the challenge with the virus,cats immunized with 107.0 TCID50/mL or higher remained largely healthy,while all cats in the control group developed clinical signs of FCV.These findings suggest that the inactivated vaccine derived from the FCV-BJ isolate exhibits strong immunogenicity and protective efficacy at a minimum immunization dose of 107.0 TCID50/mL.This strain holds promise as a candidate for vaccine production,providing a valuable reference and foundation for future re-search and development of feline calicivirus vaccines.

Objective:To analyze the clinical and genetic characteristics of a family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) caused by a new locus of HTRA1 mutation. Methods:The medical history and clinical data of a patient with CARASIL were collected, and genetic test was performed on some family members to observe the HTRA1 mutation. Results:The proband presented with cognitive impairment, suspicious lumbar lesions, and alopecia. Cranial imaging revealed extensive blank brain lesions and multiple microbleeding foci. The mother of the proband had psychiatric symptoms and stroke once, and the sixth younger sister had history of dementia and hypertension. Genetic test revealed that the proband and his two sons carried HTRA1 heterogenic mutation c.888C>G (p.I296M), and the two sons had alopecia. Conclusion:The c.888C>G(p.I296M) may be a new pathogenic mutation site of CARASIL.