The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective This study aims to investigate the impact of cultivation time on dendritic cells(DCs)and their derived exosomes′ expression of immune-related membrane proteins(CD80,MHC-Ⅰ,MHC-Ⅱ)and provides experimental evidence for future research.Methods Mouse bone marrow cells were induced to differentiate into DCs using GM-CSF and IL-4,followed by maturation stimulation withTNF-α.Exosomes were extracted using ultracentrifugation.Western blot and Amnis image flow cytometry were used to identify exosomes derived from mouse DCs.Amnis image flow cytometry was used to detect the expression of immune-related proteins CD80,CD11c,MHC-Ⅰ,and MHC-Ⅱ in mouse DCs and their exosomes.Results After 5 days of in vitro cultivation,more than 50%of dendritic cells expressed CD80,CD11c,MHC-Ⅰ,and MHC-Ⅱ,reaching the highest level on day 13.The positivity rates were as follows:CD80(97.29±0.63)%,CD11c(92.31±1.18)%,MHC-Ⅰ(97.91±0.49)%,and MHC-Ⅱ(97.91±0.49)%.The differences were statistically significant(P<0.001).The expression gradually decreased after day 13,but approximately 80%of DC cells still expressed MHC-Ⅰ and MHC-Ⅱ immune molecules on day 30.The expression levels of CD80,CD11c,and MHC-Ⅱ on the exosome membrane were highest on day 5 and then decreased overall with prolonged cultivation time,except for MHC-Ⅰ molecules.The differences were statistically significant(P<0.01).Conclusions In vitro-cultured mouse dendritic cells express high levels of immune-related membrane proteins and can be stably maintained for a long time under suitable culture conditions.The secreted exosomes also carry abundant immune-related membrane proteins,but no significant correlation was found between the immune-related proteins on the dendritic cell surface and the exosome membrane surface.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective:To explore the effects of dexmedetomidine (DEX) on postoperative pain, oxidative stress and adverse reactions in patients undergoing radical mastectomy.Methods:A total of 90 patients with breast cancer who received radical surgical treatment in our hospital from Jun. 2022 to Jun. 2023 were prospectively included as research objects and randomly divided into 3 groups with 30 patients in each group. DEX group was applied before, during and after surgery, respectively. The levels of pain visual analogue scale (VAS), Richmonation sedation score (RASS), superoxide dismu-tase (SOD) and malondialdehyde (MDA) were recorded.Results:The recovery time and extubation time in preoperative and intraoperative DEX group were significantly lower than those in postoperative DEX group, and the awakening time and extubation time in preoperative DEX group were significantly lower than those in intraoperative DEX group ( F value was 48.62 and 53.98, respectively, P<0.001). At 1 h, 6 h and 12 h after surgery, the VAS and RASS scores of patients in the preoperative and intraoperative DEX group were significantly lower than those in the postoperative DEX group, compared with those in the intraoperative DEX group. The VAS and RASS scores in the DEX group were significantly decreased ( F value: 62.34, 55.24, 69.26, 36.82, 24.20, 39.97, P<0.001). At 24h after surgery, there was no significant difference in VAS and RASS scores among the three groups ( F value was 0.45 and 0.81, respectively, P value was 0.613 and 0.418). Immediately after surgery, 24 h after surgery, 72 h after surgery, the SOD level of DEX group was significantly higher than that of DEX group before and during surgery ( F value was 29.37, 33.24, 10.35, P<0.001). MDA levels were significantly lower than those in postoperative DEX group ( F value was 30.52, 41.27, 8.26, P<0.001). There was no significant difference in the incidence of postoperative adverse reactions among all groups ( P>0.05) . Conclusion:Preoperative and intraoperative application of DEX can reduce postoperative pain and oxidative stress in breast cancer patients, help patients recover quickly after surgery, and preoperative application is superior to intraoperative application.

Objective To investigate the differences in clinical and radiographic features between severe influenza A H1N1 and H3N2 in children.Methods The clinical and radiographic data of children diagnosed with severe influenza A H1N1 and H3N2 were analyzed retrospectively.According to the pathogen subtypes,they were divided into H1N1 group(34 cases)and H3N2 group(23 cases).Differences in clinical data,laboratory results,treatment,hospitalization time,outcome,and radiographic features between the two groups were analyzed.The t-test was used for the comparison of normally distributed measurement data between the groups,and Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between the groups.Chi-square test or Fisher's exact probability method was used for the analysis of counting data,depending on the situation.Results There were differences in the season of onset,clinical and radiographic features between the two groups.H1N1 subtype mostly occurred in win-ter,and mainly manifested as respiratory symptoms(wheezing/shortness of breath)and respiratory complications(severe pneumonia).H3N2 subtype was mainly observed in summer,and more likely to involve the central nervous system(CNS),presenting with neuro-logical symptoms(convulsions),abnormal electroencephalogram,and concurrent influenza associated encephalopathy(IAE).Conclusion There are significant differences in epidemiology,clinical and radiographic features between severe influenza A H1N1 and H3N2.H3N2 has a higher probability of concurrent IAE and should be highly vigilant in clinical practice.

Objective:To investigate the relation between rs2298771 genotype in voltage-gated sodium channels 1A ( SCN1A) polymorphism and antiepileptic drug (AED) response in children with epilepsy. Methods:Sixty-two children with epilepsy admitted to Department of Neurology, Zhangjiakou First Hospital from June 2022 to December 2023 were divided into AED response group and AED resistance group ( n=31) according to their response to AED. In addition, 31 children with pharyngitis or mild gastroenteritis admitted to Department of Pediatrics at the same period were selected as control group. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the rs2298771 genotype in SCN1A polymorphism, and differences in rs2298771 genotype and allele in SCN1A polymorphism were compared among the 3 groups. Relation between rs2298771 genotype in SCN1A polymorphism and AED response was analyzed. Multivariate Logistic regression was used to analyze the influencing factors for AED response in children with epilepsy. Results:(1) Significant differences in type of first seizure and AEDs were noted between AED response group and AED resistance group ( P<0.05); compared with the AED resistance group, the AED response group had significantly lower seizure frequency, significantly longer duration after last seizure, and statistically higher proportions of children with normal EEG or with one kind of AED ( P?0.05). (2) Compared with the control group and AED response group, the AED resistance group had significantly higher rs2298771 GC genotype and G allele, and statistically lower rs2298771 AA genotype and A allele in SCN1A polymorphism ( P?0.05). (3) In the AED response group, rs2298771 AA and AG genotype in SCN1A polymorphism were positively correlated with levetiracetam ( P?0.05); in AED resistance group, rs2298771 AG genotype in SCN1A polymorphism was positively correlated with topiramate and valproic acid ( P<0.05). (4) Multivariate Logistic regression analysis showed that duration after last seizure ( OR=3.249, 95% CI=1.097-9.621, P=0.033), rs2298771 genotype in SCN1A polymorphism ( OR=9.660, 95% CI=4.680-19.970, P=0.011) and seizure frequency ( OR=0.160, 95% CI=0.032-0.804, P=0.026) were independent influencing factors for AED response in children with epilepsy. Conclusion:Epilepsy children with shorter duration after last seizure, rs2298771 GG genotype in SCN1A polymorphism, and high seizure frequency are susceptible to AED resistance; especially, AG genotype is correlated with topiramate and valproic acid.

Photon Counting Detector(PCD)is a device used to detect X-ray photons,which can directly convert the energy of photons into electrical signals to achieve photon counting and measurement.PCD-based energy spectrum computed tomography(PCD-CT)technology can provide additional energy spectral imaging information,and improve imaging quality while reducing radiation dose.Compared with energy integrating detectors(EID),PCD has advantages of high energy conversion efficiency,good imaging quality,exquisite structural design,and wide application range.It has broad application prospects in ultra-low-dose CT,specific disease diagnosis,and industrial inspection.The application of PCD-CT in spectral CT imaging was reviewed to provide a useful reference for its application in clinical medical diagnosis and industrial applications.

Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.