BACKGROUND:Platelet-rich fibrin(PRF)has many advantages,such as simple preparation,low production cost,and high safety,and has been widely used in the study of bone defect repair in oral and maxillofacial surgery,but there are problems such as too fast degradation rate and short release time of growth factors. OBJECTIVE:PRF was loaded into gelatin methacryloyl(GelMA)hydrogel and its osteogenic properties were analyzed by in vivo and in vitro experiments. METHODS:(1)New Zealand white rabbit venous blood was extracted to prepare PRF.GelMA hydrogels containing 0,0.05,0.075,and 0.1 g PRF were prepared,respectively,and were recorded as GelMA,GelMA/PRF-0.05,GelMA/PRF-0.075,and GelMA/PRF-0.1,respectively,to characterize the micromorphology and in vitro slow-release properties of the hydrogels.(2)Four kinds of hydrogels were co-cultured with MC3T3-E1 cells,respectively,and the cell proliferation activity was detected with the single cultured cells as the control.After osteogenic induction,alkaline phosphatase activity,mineralization ability,mRNA and protein expression levels of osteogenic genes(osteocalcin,osteopontin,RUNX2),ERK1/2-p38 MAPK pathway protein mRNA and protein expression levels were detected.(3)Fifteen New Zealand white rabbits were taken.Four full-layer bone defects of 8 mm diameter were prepared in the skull of each rabbit,one of which was implanted without any material(blank control group),and the other three were implanted with GelMA hydrogel,PRF,and GelMA/PRF-0.1 hydrogel,respectively.The bone defect was detected by Micro-CT and bone morphology was observed at 4,8,and 12 weeks after operation. RESULTS AND CONCLUSION:(1)Scanning electron microscopy observed that all the hydrogels of the four groups had honeycomb pore structure,and the pore size of the hydrogels decreased slightly with the increase of PRF content,but there was no significant difference between the groups.The three groups of GelMA/PRF hydrogel could release transforming growth factor β1 and insulin-like growth factor 1 at a certain rate,and the cumulative release of transforming growth factor β1 and insulin-like growth factor 1 increased significantly with the extension of time.(2)CCK-8 assay and live/dead staining showed that GelMA/PRF hydrogel could promote the proliferation of MC3T3-E1 cells.The results of alkaline phosphatase staining,alizarin red staining,and osteogenic gene detection showed that GelMA/PRF hydrogel could promote the osteogenic differentiation of MC3T3-E1 cells,and inhibit the expression of ERK1/2-p38 MAPK pathway protein,and showed a PRF content dependence.(3)Micro-CT scan showed that the bone mineral density and bone volume fraction in the bone defect of GelMA/PRF-0.1 hydrogel group were higher than those in the other three groups(P<0.05).Hematoxylin-eosin staining showed that compared with the other three groups,GelMA/PRF-0.1 hydrogel group had faster and more mature new bone formation at the bone defect.(4)These findings indicate that GelMA/PRF hydrogel has good osteogenic activity both in vivo and in vitro,which may be related to inhibiting the expression of ERK1/2-p38 MAPK pathway protein.

ObjectiveTo carry out a health technology assessment （HTA） of acupuncture for secondary dysmenorrhea （SD） caused by adenomyosis and endometriosis， in order to provide a reference for relevant medical decision-making. MethodsFrom the perspective of the health system， the assessment covers seven areas， including the technical characteristics， safety， effectiveness， economics， ethical fairness， organizational adaptability， and impact on patients and society. The results are reported accordingly. ResultsThe operational specifications of acupuncture are standardized， and the conditions for its use are clearly defined. Acupuncture has a lower overall incidence of adverse events. The main adverse events are localized pain， subcutaneous bleeding， and dizziness， with most symptoms being mild， all of which have corresponding standard treatments. No reports on occupational or environmental safety were found， and the safety operation specifications are available for reference. Compared with conventional Western medicine， acupuncture demonstrates higher effectiveness. Acupuncture may improve the quality of life scores of patients， though no significant difference was observed. The cost of acupuncture is higher than that of conventional Western medicine， but its overall economic value is greater. The informed consent information is relatively comprehensive. Most patients are aware of the potential benefits and risks of acupuncture and voluntarily opt for it. The treatment process fully respects patient privacy and human rights. The clinical application of acupuncture follows the current acupuncture medical service model， with no special requirements for the level of medical institutions. Patient accessibility and affordability are suitable. Patient satisfaction is high. Most patients indicated they would choose acupuncture again for SD. The main barriers to choosing acupuncture are psychological factors （such as fear of acupuncture）， cost， and transportation issues. Nearly 70% of patients receiving acupuncture treatment benefit from medical insurance reimbursement， with reimbursement rates generally above 50%， indicating strong social security support. ConclusionThe implementation of HTA for acupuncture in the treatment of SD， using the standards for traditional Chinese medicine （TCM）， is feasible. The implementation steps are clear， the data sources for each evaluation domain are adequate， the analysis methods are practical， and the evaluation results are comprehensive. Experts recommend that the findings be used as a reference for relevant medical decision-making.

Objective To investigate the predictive value of quantitative parameters of contrast-enhanced ultrasound (CEUS) in evaluating kidneys from donation after brain death (DBD) for the occurrence of delayed graft function (DGF) in recipients. Methods The clinical data of 134 DBD donors and 202 corresponding kidneys and recipients were retrospective analyzed. The recipients were divided into DGF group (n=39) and non-DGF group (n=163) according to the renal function after kidney transplantation. Conventional ultrasound, CEUS parameters, and clinical data were compared between the two groups. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for predicting DGF using CEUS parameters, clinical parameters, and their combination, based on the highest Youden index. The predictive ability of different parameters for DGF was evaluated. Results There were statistically significant differences in cortical peak intensity (PIc), medullary peak intensity (PIm), donor albumin (ALB), serum creatinine (Scr) after admission, and the Na⁺ concentration of recipients between the two groups (all P<0.05). The area under the curve (AUC) for predicting DGF using the combination of CEUS parameters PIc and PIm was 0.711, with an optimal cut-off value of 0.193 and a Youden index of 0.382. The AUC for predicting DGF using the combination of CEUS parameters PIc, PIm and clinical parameters was 0.808, with an optimal cut-off value of 0.191 and a Youden index of 0.517. The sensitivity and specificity were 0.769 and 0.613 for the former, and 0.769 and 0.748 for the latter, respectively. The AUC for predicting DGF using CEUS parameters PIc and PIm combined with clinical parameters was significantly higher than that using CEUS parameters PIc and PIm (P<0.05). Conclusions The CEUS quantitative parameters PIc and PIm have good predictive value in assessing kidneys from DBD donors for DGF in recipients, and the diagnostic efficacy is better when combined with clinical parameters.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Objective:To discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.

Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P＜0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.

Objective To investigate the value of thrombomodulin(TM),thrombin-antithrombin complex(TAT),α2 plasmin inhibitor-plasmin complex(PIC)and tissue plasminogen activator-inhibitor complex(t-PAIC)in the diagnosis and prognosis of neonatal disseminated intravascular coagulation(DIC).Methods Eighty-seven DIC neonates(the observation group)were included and divided into the survival group(66 cases)and the death group(21 cases)based on their outcomes at discharge.And 50 healthy newborns born in the same period were selected as the control group.The clinical data of neonates were collected,and risk factors of neonatal DIC were analyzed by Logistic regression.The differences of TM,TAT,PIC and t-PAIC levels in different groups were analyzed.The receiver operating characteristic(ROC)curve was used to analyze values of TM,TAT,PIC and t-PAIC in the diagnosis and prognosis of neonatal DIC.Results The incidence of low Apgar score,birth asphyxia,IVH,sepsis and maternal pregnancy induced hypertension syndrome(PIH)were higher in the observation group than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that low Apgar score,birth asphyxia,sepsis and PIH were independent risk factors for neonatal DIC.TM,TAT,PIC and t-PAIC levels were higher in the observation group than those in the control group(P＜0.05).ROC curve showed that the combined diagnosis value of TM,TAT,PIC and t-PAIC was better than that of single diagnosis of neonatal DIC.TM and TAT levels were higher in the death group than those in the survival group(P＜0.05),and there were no significant differences in PIC and t-PAIC levels between the two groups.Multivariate Logistic regression analysis showed that elevated TAT level was an independent risk factor for neonatal DIC prognosis.ROC curve showed that when TAT was 21.72 μg/L,the area under the curve for predicting neonatal DIC prognosis was 0.772(95%CI:0.666-0.878),and the sensitivity and specificity were 76.2%and 71.2%,respectively.Conclusion The combined application of TM,TAT,PIC and t-PAIC has important clinical value in diagnosis and prognosis evaluation of neonatal DIC.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Objective To investigate the signal abnormality of conus medullaris in patients with overactive bladder(OAB)and un-deractive bladder(UAB)by MRI diffusion tensor imaging(DTI). Methods From May,2021 to April,2023,23 patients with lower urinary tract dysfunction without trauma and supraspi-nal lesions were enrolled(case group).All patients underwent imaging urodynamics and pelvic floor electromy-ography.Based on the bladder contraction during the filling phase of urodynamics,the patients were divided into UAB group and OAB group.Eight healthy subjects were included as the control group.All participants under-went T10 to L5 spinal segment MRI scans and DTI scans.The position of conus medullaris was determined by comparing the DTI sequences with the MRI scans.The fractional anisotropy(FA),apparent diffusion coefficient(ADC),and relative anisotropy(RA)of the conus medullaris intermediate segment were compared. Results Twelve cases were in UAB group,and eleven in OAB goup.Abnormalities were found in the pelvic floor elec-tromyography in the case group.There was significant difference in sacral reflex arc nerve conduction testing be-tween UAB and OAB groups(P = 0.036).Compared with the control group,ADC increased(t = 2.185,P = 0.037)in the case group;FA decreased(t = 3.439,P = 0.005)and ADC increased(t = 4.582,P<0.001)in UAB group. Conclusion DTI is helpful to find the potential lesion of spinal cord in patients with lower urinary tract dysfunction.FA and ADC are valuable indicators for the diagnosis of conus medullaris injury.