Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To explore the risk factors for obstetric septic shock.Methods The clinical data of 122 obstetric sepsis patients from Jan.2013 to Apr.2025 were retrospectively analyzed.The patients were assigned to shock group(n=26)or non-shock group(n=96)based on whether they progressed to septic shock.Variables including age,body mass index,multiple pregnancy,sequential organ failure assessment(SOFA)score,organ dysfunction status,white blood cell count(WBC),neutrophil count(NEU),neutrophil ratio,platelet count,procalcitonin,C-reactive protein,lactate(Lac),and D-dimer were recorded.Multivariate logistic regression analysis was used to identify the independent risk factors for obstetric septic shock.The predictive efficacy of these factors was evaluated using receiver operating characteristic(ROC)curve analysis.Results The proportions of patients aged≥35 years,and those with respiratory,cardiac,or central nervous system dysfunction,were significantly higher in the shock group than in the non-shock group,and the SOFA score,WBC,NEU,neutrophil ratio and Lac level were significantly higher in the shock group(all P＜0.05).Multivariate logistic regression analysis showed that increased NEU(odds ratio[OR]=1.093,95%confidence interval[CI]1.022-1.169,P=0.010)and age≥35 years(OR=3.433,95%CI 1.112-10.602,P=0.032)were independent risk factors for obstetric septic shock.ROC curve analysis showed that NEU had predictive value for obstetric septic shock(area under curve=0.741,95%CI 0.634-0.848),with an optimal cut-offvalue of 17.17×109/L.Conclusion Increased NEU and age≥35 years are independent risk factors for obstetric septic shock.NEU has predictive value for the development of obstetric septic shock and may serve as an important indicator for clinical assessment and timely treatment.

Objective To analyze the temporal trend of thyroid cancer incidence in China from 1992 to 2021 and evaluate the impact of age,period and cohort on the incidence.Methods Based on the Global Burden of Disease 2021,the trend changes of age-standardized incidence rate(ASIR)of thyroid cancer in China from the period were analyzed,and the obtained data were further analyzed with Joinpoint regression and age-period-cohort analysis.Auto regressive integrated moving average(ARIMA)model was applied to predict the incidence of thyroid cancer in China in the next 20 years.Results The ASIR of thyroid cancer among males was increased from 0.70/100 000 to 2.11/100 000 between 1992 and 2021,with an average annual percent change(AAPC)of 3.93%(95%CI:3.86%～4.00%,P<0.001);For the females,the ASIR was elevated from 1.91/100 000 to 2.87/100 000 in the time,with an AAPC of 1.43%(95%CI:1.36%～1.50%,P<0.001).On the age effect,the overall variation in ASIR among the females was minor,and that in the males reached its peak in the≥85-years-old group,with a rate of 230.51/100 000.Regarding the period effect,the risk of thyroid cancer incidence in the males and females changed with the period and exhibited a temporal increase,and the incidence risk was consistently higher in the males than the females across different periods.Taking the incidence risk during 1992 and 1996 as a reference(RR=1),the males(RR=2.94,95%CI:2.78～3.11)and the females(RR=1.37,95%CI:1.32～1.42)had the highest risk of thyroid cancer in the period from 2017 to 2021.On the cohort effect,the risk of thyroid cancer in both sexes showed an increasing trend with cohort change.When taking the cohort during 1992 and 1996 as a reference(RR=1),the females in the pre-1986 cohort exhibited a higher risk of incidence than the males,but in the post-1996 cohort,the males demonstrated a greater risk of incidence than the females.The males in the 2012-2016 cohort had the highest risk of thyroid cancer when compared to the reference group(RR=2.54,95%CI:1.80～3.57),and the females in the cohort from 1992 to 2016 had higher risk of thyroid cancer than the reference group,though no statistical differences were observed.The ARIMA model prediction analysis found that the ASIR of thyroid cancer in males and females in China would continue to increase from 2022 to 2041,and the ASIR of thyroid cancer in males would reach 2.79/100 000(95%CI:1.96～3.61),and the ASIR of thyroid cancer in females would reach 3.54/100 000(95%CI:3.02～4.06)by 2041.Conclusion Between 1992 and 2021,the ASIR of thyroid cancer in China has exhibited a consistent upward trend,with the females having a higher ASIR than the males.However,the risk of developing thyroid cancer is higher in men who are older and those who were born more recently.In the next 20 years,the incidence of thyroid cancer among both men and women in China is projected to continue to rise,and the situation for prevention and control will be challenging.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective To investigate the effect of mulberry anthocyanin on the morphology and func-tion of vascular endothelial cells(VEC)and its possible mechanism at the level of autophagy.Methods VEC were cultured in vitro and divided into 5.5/0 mmol/L control group,11/0.125,22/0.250,33/0.500,44/1.000,55/2.000 mmol/L high glucose/high fat groups.The cell functional levels and autophage levels in each group were detected.The optimal high glucose/high lipid concentration was selected as the VEC function inju-ry model group.10,25,50 μmol/L mulberry anthocyanins were added into the model group for processing and divided into the low,middle and high concentrations of mulberry anthocyanin groups.The effects of mulberry anthocyanin on the morphology,function and autophagy of VEC in high sugar and high fat stress were ob-served.Then the autophagy regulator(rapamycin)was added to study its action mechanism.HE staining was used to observe the number and morphology of cells,the CCK-8 assay was used to detect the viability of VEC,the flow cytometry was used to detect the level of reactive oxygen species(ROS)in VEC,the Western blot was used to detect the expression level of Beclin-1 and p62 proteins in VEC,and the kit method was used to detect the level of nitric oxide(NO)and endothelin-1(ET-1)in VEC.Results Compared with the control group,the number and morphology of cells in the middle and high concentrations of high glucose/high fat groups were changed,the cell viability,p62,NO levels were significantly decreased(P<0.05),while the ROS,ET-1,and Beclin-1 expression levels were increased significantly(P<0.05).Compared with the model group,the number of cells in the mulberry anthocyanin groups was increased,morphology was improved,the cellular viability,p62 and No levels were significantly increased,and ROS,Beclin-1 and ET-1 levels were significantly decreased(P<0.05).Compared with the high concentration mulberry anthocyanin group,the cells number was decreased af-ter adding rapamycin,the morphology changed to be irregular,the NO level was decreased,and the ET level was increased(P<0.05).Compared with the control group,the p-phosphatidylinositol 3-kinase(PI3K)and p-protein kinase B(Akt)relative expression levels in the model group were significantly decreased(P<0.05);compared with the model group,the p-PI3K and p-Akt relative expression levels in the high concentration mulberry anthocyanin group were significantly increased(P<0.05).Conclusion Mulberry anthocyanin could in-hibit autophagy by activating the PI3K/Akt/mammalian target of rapamycin(mTOR)signaling pathway and improve the morphology and function of VEC under high glucose and lipid stress.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.