Chronic glomerulonephritis （CGN） is a common clinical chronic glomerular disease caused by autoimmune reaction， the pathogenesis of which is complex and has not been fully elucidated. There is no specific treatment method in modern medicine. The establishment of an animal model of CGN in accordance with its characteristics in western medicine and traditional Chinese medicine will help to reveal the pathogenesis of CGN， rate drugs， and improve the treatment plan. Based on the clinical diagnostic criteria of CGN， the paper establishes the syndrome differentiation criteria of CGN for Chinese and western medicine. Through summarizing the literature on animal models of CGN and making a further analysis， it is found that the CGN models are mainly modeled using rats with the methods of single-factor induction or two-factor induction， and the main manifestation of the disease characteristics is nephritis-related symptoms. The single-factor-induced or two-factor-induced CGN rat models have a high fitting degree with the clinical characteristics in western medicine， but the fitting degree is insufficient with the clinical characteristics in traditional Chinese medicine. In addition， the CGN models with syndromes of traditional Chinese medicine are dominated by Qi deficiency in the spleen and kidney and Qi deficiency in the lung and kidney， while models for Yang deficiency in the spleen and kidney， Yin deficiency in the liver and kidney， and deficiency of both Qi and Yin are slightly insufficient. Therefore， it is important to prepare a new and improved animal model of CGN， so that a preclinical model can be provided for the exploration of the pathogenesis of CGN in western medicine and traditional Chinese medicine and its therapeutic research.

Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE-/-mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/-mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

Programmed cell death protein ligand-1(PD-L1)is an important immune checkpoint molecule that plays an important role in regulating the body's immune response.Several clinical studies have shown that the expression level of PD-L1 in tumors is closely related to the efficacy of immune checkpoint inhibitors.Due to the spatial and temporal heterogeneity of tumors,immunohistochemical methods commonly used in clinical practice cannot accurately and comprehensively reflect the ex-pression level of PD-L1 in patients.Given that nuclear-medicine molecular imaging technology can noninvasively,real-time,dy-namically and visually monitor the expression level of PD-L1 in vivo at the molecular level,this article mainly focuses on the re-search of peptide-based radiolabeled molecular probes targeting PD-L1,with the aim of providing guidance for the search of no-vel peptide molecular probes for immunoimaging as well as for the screening of immunotherapy-suitable patients and evaluation of therapeutic efficacy,and other clinical applications.

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 organizational and operational models of collaborative construction of Research and Development (R&D) platforms by innovative hospitals and enterprises, aiming to provide support and a guarantee for accelerating scientific and technological innovation and the transformation of achievements.Methods:Taking the co-construction of a joint R&D platform by Beijing Tiantan Hospital with enterprise as a case study, this study discussed the necessity of platform construction, and from the perspective of management practices, focusing on analyzing construction models, operational management, achievement attribution, and profits distribution, as well as other critical issues in platform construction.Results:Hospitals and enterprises agreed on the cooperation and co-construction model by signing an agreement. The management committee system and the centre director responsibility system were important operation and management mechanisms. The intellectual property rights of the outcomes generated by the cooperative R&D based on the joint R&D platform were co-owned by the cooperative parties. Data security, close communication, and high-quality research output were the critical issues for the sustainable cooperation between hospitals and enterprises. At the same time, this article proposed optimized management measures to address existing problems in the cooperation of the hospital-enterprise joint R&D platform.Conclusions:The hospital-enterprise joint R&D platform, as a new model of innovative collaboration between hospitals and businesses, held significant importance for tackling ″bottleneck″ technologies in medical science, the implementation of medical scientific and technological outcomes, and the cultivation of interdisciplinary talents.

OBJECTIVE To establish the fingerprint of the ethanol extract from Callicarpa nudiflora， analyze its anti- respiratory syncytial virus （RSV） activity in vitro， and study the relationship between spectrum and effect. METHODS Using 10%， 30%， 50%， 70% and 90% ethanol as solvent， 20 batches of ethanol extracts from 4 batches of C. nudiflora were prepared. The fingerprints for 20 batches of ethanol extracts from C. nudiflora were mapped by ultra-high-performance liquid chromatography （UPLC）， and the similarity evaluation was conducted by using the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition）. The cytopathic effect method and MTT method were used to investigate the in vitro inhibitory activity of the ethanol extracts from C. nudiflora on RSV. Pearson correlation analysis， grey correlation degree and orthogonal partial least squares （OPLS） analysis were used to study the spectrum-effect relationship. RESULTS There were 25 common peaks in 20 batches of ethanol extracts from C. nudiflora， and the similarities ranged from 0.912 to 0.998， and the RSDs of common peak areas were 33.54%-162.28%. The average values of IC50 for RSV of 20 batches of ethanol extracts from C. nudiflora were 9.55-272.23 μg/mL. The results of Pearson correlation analysis， grey correlation analysis and OPLS analysis showed that the Pearson correlation coefficients （P＜0.05） of the common peaks 8， 10， 12， 16， 18-19， 22-24 with pharmacodynamic indicators and regression coefficients were all negative， the correlation coefficients were all greater than 0.6， and the values of variable importance in projection were all greater than 1. CONCLUSIONS Twenty batches of ethanol extracts from C. nudiflora have similar components but significant differences in content， and exhibit different degrees of anti-RSV activity in vitro. The corresponding components of common peaks 8， 10， 12， 16， 18-19， 22-24 may be the characteristic components of anti-RSV of C. nudiflora.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Objective:To study the factors influencing transient hypothyroxinemia (TH) in one premature twin.Methods:This retrospective study enrolled 283 sets of preterm twins who were born at the gestational age of 26-36 weeks and admitted to the Neonatology Department of the Second Affiliated Hospital of Wenzhou Medical University from June 2009 to September 2021. The levels of thyroxine (T 4), triiodothyronine (T 3) and thyroid stimulating hormone (TSH) were detected at 11-20 d after birth. Finally, 47 sets of twins were further analyzed, in which one twin met the diagnostic criteria of TH (TH group, n=47) and the other twin with exclusion of the diagnosis (control group, n=47). Pearson correlation was used to analyze the correlation of T 4 with gestational age and birth weight. Paired t test, Wilcoxon signed-rank test or McNemar test, and conditional logistic regression were used to analyze the factors influencing TH in premature twins. Results:The gestational age and birth weight of the 47 sets of preterm twins (94 cases) were (31.4±2.3) weeks (26-36 weeks) and (1 611.9±389.3) g (800-2 510 g), respectively. There were 35 sets of dizygotic twins, 11 sets of monozygotic twins, and one set of twins with unknown zygosity. The serum T 4 level in premature infants was positively correlated with the gestational age and birth weight (the correlation coefficients were 0.209 and 0.376, respectively, both P<0.05). Univariate analysis showed that compared with the control group, the factors influencing TH in premature infants ( P<0.1) included female [29.8% (14/47) vs 14.9% (7/47), χ2=3.27 ], bronchopulmonary dysplasia [31.9% (15/47) vs 19.1% (9/47), χ2=3.13], birth weight [(1 547.9±348.0) vs (1 676.0±420.5) g, t=－3.61], white blood cell count [(10.0±3.3)×10 9/L vs (10.9±3.3)×10 9/L, t=－2.19] and vitamin D level [(42.8±12.1) vs (45.9±16.6) nmol/L, t=－1.76]. The data on vitamin D were incomplete and after excluding the factor, the logistic regression showed that female was a risk factor ( OR=18.388 95% CI: 1.317-256.743); while higher birth weight was a protective factor ( OR=0.996, 95% CI: 0.993-0.999). In order to exclude the influence of monozygotic twins on gender, 11 sets of monozygotic twins and one set with unknown zygosity were excluded from multivariate analysis. The results suggested that female was a risk factor ( OR=18.527, 95% CI: 1.209-283.820), while higher birth weight was a protective factor ( OR=0.996, 95% CI: 0.992-1.000). Conclusion:Female and birth weight are the factors influencing TH at 11-20 d after birth in one preterm twin.