This paper summarizes Professor LIU Fengbin's clinical experience in treating autoimmune liver disease （AILD） using the method of nourishing yin and removing stasis based on stage differentiation. He believes that the pathogenesis of AILD generally involves both deficiency in essence and excess in manifestation， with essence deficiency often presenting as liver and kidney yin deficiency， which may progress to spleen deficiency and yang deficiency over time. The excess manifestation commonly includes qi stagnation， blood stasis， damp-heat， and phlegm toxicity. Clinically， he advocates for the treatment principle of nourishing yin and removing stasis. On the foundation of nourishing liver and kidney yin， different pathological factors causing stasis are eliminated according to their nature. Treatment is also tailored to different stages of AILD. In the early and asymptomatic stages， liver qi stagnation and spleen deficiency are prominent， warranting a therapeutic approach of soothing the liver， regulating qi and strengthening the spleen. The modified Chaishao Qizhi Decoction （柴芍气滞汤） is used. During the symptomatic stage， pathogenic factors become more pronounced， often accompanied by a significant deficiency of vital qi， with damp-heat， water retention， and phlegm toxicity as key pathological features. The treatment should focus on strengthening the spleen and dispelling dampness， using modified Sijunzi Decoction （四君子汤） combined with Yinchen Wuling Powder （茵陈五苓散）. In the liver function decompensation stage， vital qi is severely deficient while pathogenic factors persist， with damp-heat， phlegm toxicity， and blood stasis obstructing the liver collaterals. Treatment should focus on nourishing blood， softening the liver， strengthening the spleen， and resolving stasis， using the modified Ruangan Yangxue Decoction （软肝养血汤）. Throughout the treatment process， emphasis is placed on tonifying the liver and kidneys while protecting yin fluids.

Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Objective To analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Pancreatic cancer is a disease with a high fatality rate， with a five-year survival rate of no more than 10% and a significantly increasing annual mortality rate. The common pathogenesis factors of pancreatic cancer are family inheritance， diet， pancreatitis， obesity， etc.， among which， family inheritance of pancreatic cancer is the main reason， and about 7%-10% of patients have family inheritance. Surgery is an effective way to treat pancreatic cancer in patients and improve their survival， but most people are diagnosed with pancreatic cancer at intermediate and advanced stages and lose the opportunity for surgical treatment. Therefore， radiotherapy， interventional therapy， supportive treatment， immunotherapy， and other treatments are used clinically to relieve symptoms and prolong the survival of patients. The commonly used clinical drug is gemcitabine. Although it can inhibit tumor growth and improve the condition， it can bring side effects such as bone marrow suppression， rash， digestive tract side effects， and drug resistance. The damage of these side effects to the human body is systemic. Chinese medicine can be used alone or in combination with other treatment methods to reduce the toxic and side effects of chemotherapy， restore the physical energy of patients， and reduce its related complications. Chinese medicine contains a large number of active ingredients， including alkaloids， flavonoids， saponins， phenolic acids， and organic acids， with anti-inflammatory， anti-viral， anti-tumor， and other curative effects. Many clinical studies of traditional Chinese medicine （TCM） on cancers have verified that TCM plays a positive role in tumor prevention and treatment， especially in improving and controlling clinical symptoms， and also plays a good detoxification effect on radiotherapy and chemotherapy， with good results achieved in improving bone marrow suppression， improving immunity， improving quality of life， and prolonging survival. This paper reviewed the anti-pancreatic cancer mechanism of Chinese medicine monomers based on literature in China and abroad， aiming to provide new potential drug candidates for the treatment of pancreatic cancer.

Objective:To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes.Methods:A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality.Results:During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR=1.97,95 %CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR=1.22, 95 %CI 1.08-1.39, P=0.002). Conclusions:Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

Objective　To investigate the role and molecular mechanism of long intergenic non-coding RNA 1116 (LINC01116) in hippocampal astrocytes of acute ischemic stroke (AIS).Methods　The expressions of LINC01116 and miR-203 in serum of 131 AIS patients before and after thrombolysis were detected by real-time fluorescence quantitative PCR.The regulatory effect of LINC01116 on miR-203 was detected by dual-luciferase reporter gene and RNA-binding protein immunoprecipitation assay.Human hippocampal astrocytes (hHA) were applied to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) model and were treated with LINC01116 interference and LINC01116 combined with miR-203 interference.The changes of cell proliferation,cell apoptosis,production of reactive oxygen species (ROS),activity of lactate dehydrogenase (LDH),and inflammatory factors were detected by CCK-8,TUNEL and Western blotting,ROS assay,LDH assay,and enzyme-linked immunosorbent assay,respectively.Results　The expressions of LINC01116 and miR-203 in serum after thrombolysis were higher and lower than those before thrombolysis,respectively,and the expressions of LINC01116 and miR-203 were negatively correlated (P<0.05).LINC01116 inhibited miR-203 expression by sponge of miR-203 (P<0.05).LINC01116 interference alleviated the OGD/R-induced injury of hHA cells,which manifested as elevated cell proliferation ability,decreased cell apoptosis rate,decreased protein expressions of cleaved caspase-3 and Bax but raised protein expression of Bcl-2,reduced ROS production,decreased LDH activity,and downregulated TNF-α,IL-1β and IL-6 concentrations but upregulated IL-4,IL-10 and IL-13 concentrations (P<0.05).miR-203 interference reversed the protective effect of LINC01116 interference on the OGD/R-induced injury of hHA cells (P<0.05).Conclusions　LINC01116 promotes the OGD/R-induced injury of hHA cells by targeting miR-203,suggesting that the LINC01116/miR-203 pathway might be a potential therapeutic target for AIS.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

OBJECTIVES: The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification. METHODS: The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model. RESULTS: This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm. CONCLUSIONS The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.
Artificial Intelligence ; Diabetes Mellitus ; Diabetic Foot ; Humans