BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

Objective:To investigate the effects of 3 adhesives on the bond force and durability of polished and glazed zirconia ceram-ics to orthodontic metal brackets respectively.Methods:Universal adhesives,Single Bond Universal(SBU)and Prime&Bond Universal(PBU)were respectively used to bond polished and glazed zirconia to metal braces of maxillary central incisors using TransbondTM MIP(TM)as the control.The shear bond strength(SBS),the fracture morphology and adhesive residual index(ARI)were examed after wa-ter bath or water bath-thermal cycling storage.Results:The adhesive(P＜0.001)and storage conditions(P＜0.001)significantly af-fected the shear bond strength of zirconia to brackets.There was no significant difference between the polished or glazed groups(P=0.09).SBU showed the stronger SBS and lower ABI,there were significant differences in ARI scores among the 3 cements(P＜0.001).Conclusion:SBU may have better bonding performance than PBU and TM in the orthodontic bonding of polished or glazed zir-conia surfaces to the zirconia ceramics.

Objective To evaluate the absence of corpus callosum(ACC)and intracranial accompanying abnormalities in fetus via prenatal MRI.Methods A total of 61 cases of fetal ACC diagnosed by prenatal MRI were analyzed retrospectively.The types and numbers of intracranial accompanying abnormalities were observed,and the probability of accompanying abnormalities was counted.According to whether the corpus callosum was completely absent,all cases were divided into complete ACC and partial ACC.Statistical differences of probability of accompanying abnormalities between the two groups were analyzed.Results A total of 54.1%(33/61)patients were complicated with other intracranial abnormalities,among which the most common was cerebral cortical dysplasia,accounting for 26.2%(16/61).The probability of complete ACC and partial ACC complicated with other intracranial abnormalities was 63.4%(26/41)and 35.0%(7/20),respectively,and there was statistical difference in intracranial abnormalities between complete ACC and partial ACC(χ2=4.37,P=0.037).The probability of complete ACC and partial ACC complicated with cerebral cortical dysplasia was 39.0%(16/41)and 5.0%(1/20),respectively,and there was statistical difference in cerebral cortical dysplasia between complete ACC and partial ACC(χ2=7.74,P=0.005).Conclusion MRI can accurately diagnose the fetal ACC and intracranial accompanying abnormalities.Complex ACC is more common than isolated ACC.Compared with partial ACC,complete ACC is more likely to be complicated with other intracranial abnormalities,and cerebral cortical dysplasia is the most common,which provides reliable diagnostic basis for fetal prognosis in clinical practice.

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg^-1） and ARP （1.2， 0.3 g∙kg^-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg^-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Objective To investigate the expression of long non-coding RNA(lncRNA)CCAT2 and o-varian cancer domain-containing protease 1(OTUD1)in multiple myeloma(MM)tissue and their correlation with clinicopathological characteristics and prognosis of MM.Methods A total of 132 patients with MM(MM group)diagnosed and treated in this hospital from April 2018 to April 2020 were selected.Seventy patients with non-hematological disease who underwent bone marrow puncture without abnormal bone marrow func-tion during the same period served as the control group.The real-time fluorescence quantitative PCR was used to detect the expression levels of lncRNA CCAT2 and OTUD1 mRNA in bone marrow tissue.The Pearson correlation was performed to analyze the correlation between lncRNA CCAT2 and OTUD1 mRNA expression in bone marrow tissues.The expression differences of lncRNA CCAT2 and OTUD1 mRNA were compared a-mong the MM patients with different clinical and pathological characteristics.The Kaplan-Meier curve was used to analyze the difference of prognosis among the MM patients with different lncRNA CCAT2 and OTUD1 mRNA expressions.The Cox regression was performed to analyze the factors affecting the prognosis in MM patients.Results The expression level of lncRNA CCAT2 in the bone marrow tissue of the MM group was significantly higher than that of the control group(2.31±0.67 vs.0.85±0.24),while the expression level of OTUD1 mRNA in the MM group was lower than that of the control group(1.22±0.37 vs.2.54±0.75),and the differences were statistically significant(t=17.624,16.760,all P＜0.001).The lncRNA CCAT2 expression level in the bone marrow tissue of the MM group had significantly negative correlation with the OTUD1 mRNA expression level(r=-0.731,P＜0.001).The lncRNA CCAT2 and OTUD1 mRNA expression levels had statistical differences among the MM patients with different ISS stages and β2-micro-globulin levels(P＜0.001).The 3-year overall survival rates of the high and low expression groups of ln-cRNA CCAT2 were 42.19％(27/64)and 66.18％(45/68),respectively.The 3-year overall survival rates of the high and low expression groups of OTUD1 mRNA were 72.31％(47/65)and 37.31％(25/67)respective-ly.The 3-year cumulative survival rate of MM patients in the lncRNA CCAT2 low expression group was sig-nificantly higher than that in the lncRNA CCAT2 high expression group,and the difference was statistically significant(Log Rank X2=7.151,P=0.007).The 3-year cumulative survival rate of MM patients in the OTUD1 mRNA low expression group was significantly lower than that in the OTUD1 mRNAhigh expression group(Log Rank x2=13.667,P＜0.001).The ISS stage Ⅲ and lncRNA CCAT2 high expression were the risk factors affecting the prognosis of MM patients(P＜0.01),while the OTUD1 mRNA high expression was the protective factor.Conclusion The lncRNA CCAT2 expression level in bone marrow tissue of the MM pa-tients is increased and OTUD1 expression level is decreased,the both are associated with adverse clinical and pathological characteristics of MM and independent factors affecting the prognosis of MM patients.

Objective:To explore the use of near-infrared autofluorescence probe (NIRAF-P) and its application in identifying parathyroid glands during surgery.Methods:A total of 68 patients undergoing thyroid surgery at Peking Union Medical College Hospital and Beijing Longfu Hospital between Dec. 2023 and Jun. 2024 were selected. During the operation, the near-infrared parathyroid gland detector was used to identify the parathyroid gland tissue to be tested, and histopathological examination was performed. The positive predictive value and accuracy of the near-infrared parathyroid gland detector were analyzed.Results:A total of 111 parathyroid glands were identified in 68 patients, and the positive predictive value and accuracy of the NIRAF-P were 95.5% and 94.6%, respectively.Conclusions:The NIRAF-P has high accuracy in identifying parathyroid glands. The standardized application of the NIRAF-P can help improve the efficiency of identifying parathyroid glands during surgery.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the construction and practice of an intelligent prevention and treatment system for venous thromboembolism (VTE) in grassroots hospitals. Methods Based on relevant guidelines and expert consensuses on VTE prevention and treatment, domestic and foreign literature was reviewed. A research and development team composed of clinical experts in VTE prevention and treatment, medical and nursing quality management experts, and information engineers conducted investigations and research in surrounding grassroots hospitals. Through evidence-based research and surveys, the team identified relevant business needs, user needs, and functional requirements of grassroots hospitals, and finally formulated a detailed design plan. The main program of system was written in Java. The interface obtained data from the hospital's data platform through Webservice and view interfaces. To prevent issues of repeated data extraction when multiple applications perform time tasks to assess the same patient during later server usage and expansion, the XXL-JOB distributed task scheduling platform was adopted to handle VTE assessments by medical staff. Results After the clinical application of the intelligent VTE prevention and treatment system, the bleeding risk assessment rate increased from 26.20% at the initial system launch in January 2023 to 83.04% by the end of 2023. In January 2023, the implementation rates of mechanical prevention, pharmacological prevention, and combined prevention for medium-to-high-risk VTE patients were 21.39%, 16.39%, and 5.26%, respectively, which increased to 51.75%, 25.50%, and 25.65% in December 2023. Conclusion The VTE prevention and treatment software system developed by grassroots hospitals can improve development efficiency, enhance the clinical practicality of the system, reduce the workload of medical staff, promote standardization and normalization in VTE prevention and treatment, strengthen closed-loop management of medical quality for VTE as a single disease, and effectively improve the prevention and treatment capabilities and levels of VTE within hospitals.

Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.

Objective: To investigate the clinicopathologic features and prognosis of the patients who had clear cell renal cell carcinoma (CCRCC) with metastasis to the pancreas. Methods: From Jan, 2000 to Dec, 2018, 18 patients with clear cell renal cell carcinoma (CCRCC) and had pathologically diagnosed metastasis to the pancreas were enrolled at Peking Union Medical College Hospital. The clinical and pathological data were retrospectively analyzed. Results: 11 out of 18 patients were male, and the other 7 were female. The average age of onset of CCRCC was 51.4 years. 8 cases (44.4%) occurred in the left kidney, and the other 10 cases (55.6%) with right kidney tumor. Three patients had synchronous pancreatic metastasis, and the other 15 patients had metachronous pancreatic metastasis. The median time from CCRCC onset to pancreas metastasis was 156 months. The main complaints of pancreas metastasis were abdominal pain, jaundice, gastrointestinal bleeding, nausea, weakness, loss of weight and so on. Seven patients (38.9%) had single lesion of pancreas, while 11 patients (66.1%) had multiple lesions of pancreas. Nine patients (50%) had other organs metastasis besides pancreatic metastasis at the same time. Five patients underwent pancreatic metastasis resection, while 15 patients received oral tyrosine kinase inhibitor(TKI). The mean follow-up was 171.7 months(1~361.5 months) and 5 patients died. The median overall survival (mOS) was 122 months, and the 5 year-survival rate was 81.4%. In univariate analysis, synchronous metastasis to the pancreas, relapse after 10 years, Memorial Sloan Kettering Cancer Center prognostic index, International Metastatic Renal Cell Carcinoma Database Consortium index were all significant parameters for patients′survival. Conclusions Metastasis to the pancreas from clear cell renal cell carcinoma were rare. These patients had better survival outcomes, especially those relapsing after ten years. Pancreatic metastasis resection had no significant benefit on patient′s survival.