Hepatic fibrosis（HF） is a common pathological link of a variety of chronic hepatic diseases， and its complex pathological mechanism and prolonged clinical course pose a major challenge to modern medicine. Modern conventional therapies for HF cannot reverse the pathological vascular remodeling of the liver， and targeted vascular treatment for HF is a current research hotspot. There is a contradiction between the inhibition of pathological repair and the promotion of physiological regeneration with a single targeted therapy. The dynamic equilibrium concept of "achieving equilibrium of Yin and Yang" of traditional Chinese medicine can provide a new treatment strategy， and multi-target traditional Chinese medicine compounds can achieve two-way regulation of pathological mechanisms. According to the research on the modernization of traditional Chinese medicine， the "collaterals and vascular system" are highly compatible in structure and function， and they can guide the treatment of HF at different stages by identifying their common pathological links in HF. The intrahepatic collaterals are an important component of the hepatic collaterals， and the theory of "hepatic collateral disease" based on this physiology has important guiding significance for the clinical diagnosis and treatment of HF. Hepatic sinusoidal obstruction caused by endothelial dysfunction in the early stage of HF is a pathological manifestation of stagnant nutrient Yin in collateral passages. It can be treated by diffusing Qi to resolve stagnation and promoting circulation to unblock collaterals. Repeated stimulation of angiogenesis by hypoxia and inflammation in the medium stage is the pathological manifestation of lingering stagnation of damp and heat in collateral passages. It can be treated by clearing and draining damp and heat， eliminating turbidity， and unblocking collaterals. Pathological vascular remodeling induced by hemodynamic abnormalities in the later stage is a pathological manifestation of the consumption of collateral passages by pathogenic toxins. At this stage with excessive pathogenic factors and deficient healthy Qi， combined therapy of dredging and nourishing is adopted to eliminate toxins， resolve blood stasis， nourish Yin， and supplement Qi simultaneously. Moreover， the holistic concept of harmony between human and nature in traditional Chinese medicine emphasizes the time， place， and treatment based on individual conditions， so the practical application of the theory should consider the specific regional characteristics. This paper aims to discuss the characteristics of pathogenesis， treatment principles， prescriptions， and medicines in different stages of HF based on the correlation between "collaterals and vascular system" as well as the theory of "hepatic collateral disease". It was proposed that Qi deficiency and collateral obstruction were the core pathogenesis of HF， and that hepatic collateral damage was the core pathological basis for the deterioration and prognosis of HF. The scientific connotation and pathogenesis evolution of collateral damage and mass generation in HF were discussed. Sichuan was taken as an example to investigate the treatment of HF according to local conditions， providing new ideas for the treatment of HF.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.

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OBJECTIVE: To identify the risk factors for acute respiratory distress syndrome (ARDS) in geriatric patients following gastrointestinal perforation surgery, and constructed a model to validate its predictive value. METHODS: A retrospective analysis was conducted. The clinical data of geriatric patients (aged ≥ 60 years) after gastrointestinal perforation surgery admitted to the intensive care unit (ICU) of Hebei General Hospital from October 2017 to October 2024 were enrolled. Two groups were divided according to whether ARDS occurred postoperatively, and the differences in each index between the groups were compared. Lasso regression and multifactorial Logistic regression analyses were used to identify independent risk factors for the development of ARDS, and a prediction model was constructed based on these, which was presented using a nomogram. The receiver operator characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) were plotted to evaluate the discrimination, accuracy, and clinical practicability of the model. RESULTS: A total of 155 geriatric patients following gastrointestinal perforation surgery were ultimately included in the analysis, among whom 43 developed ARDS, with an incidence rate of 27.7%. There were significantly differences in age, body mass index (BMI), acute kidney injury comorbidity, heart rate, onset time, the duration of surgery, the site of perforation, seroperitoneum, amount of bleeding, shock comorbidity, central venous pressure (CVP), C-reactive protein, and albumin between ARDS and non-ARDS groups. Lasso regression identified nine significant predictors: age, BMI, acute kidney injury comorbidity, onset time, seroperitoneum, shock comorbidity, CVP, hemoglobin, and albumin. Multivariate Logistic regression analysis identified BMI [odds ratio (OR) = 1.310, P < 0.001], hemoglobin (OR = 1.019, P = 0.045), seroperitoneum (OR = 1.001, P = 0.017), and albumin (OR = 0.871, P < 0.001) as independent risk factors for the occurrence of ARDS. A prediction model was constructed based on the above four independent risk factors, and the ROC curve showed that the area under the curve (AUC) of the model for predicting the occurrence of ARDS was 0.885 [95% confidence interval (95%CI) was 0.824-0.946], and internal validation was performed using bootstrap resampling (Bootstrap 500 times), which showed that the AUC value of the model was 0.886 (95%CI was 0.883-0.889). Calibration curves revealed excellent concordance between observed outcomes and model predictions. DCA indicated a high net benefit value for the model, which has good clinical utility. CONCLUSIONS BMI, hemoglobin, seroperitoneum, and albumin were identified as independent risk factors for ARDS in geriatric patients following gastrointestinal perforation surgery. The prediction model constructed using these four indicators facilitates early identification of high-risk individuals by clinicians.
Humans ; Respiratory Distress Syndrome/etiology* ; Retrospective Studies ; Aged ; Risk Factors ; Logistic Models ; Postoperative Complications ; Intestinal Perforation/surgery* ; Male ; ROC Curve ; Female ; Middle Aged ; Intensive Care Units ; Nomograms

The hepatic vascular microenvironment(HVM)plays a pivotal role in maintaining liver function homeostasis,including metabolism,detoxification,and coagulation.The maintenance of HVM homeostasis is governed by an intricate interplay of mechanical forces,chemical signals,and neuroelectrophysiological conduction.Recent studies have shown that an imbalance in HVM promotes the progression of chronic liver disease(CLD),which is characterized by sinusoidal capillarization,vascular deformation and remodeling,and the arterialization of blood supply.This review sum-marizes the dynamic regulatory mechanisms that underpin HVM in physiological conditions,and the primary pathological manifestations observed at various stages of CLD progression,aiming to provide a robust framework for the development of therapeutic strategies targeting HVM homeostatic imbanlance in CLD.

Hypersplenism is an important complication of cirrhotic portal hypertension, and splenectomy is an important means to treat hypersplenism in cirrhosis. It is realized that hypersplenism played a pathological role in the course of cirrhosis. This article analyzes and compares the changes in the condition of patients with cirrhosis between splenectomy with and without hyperfunction, and comprehensively discusses the pathological role and mechanism of hypersplenism in the course of cirrhosis, in order to strengthen the clinical prevention and treatment of hypersplenism in cirrhosis and to better improve the condition and prognosis of patients with cirrhosis.

Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.

Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.

BACKGROUND:The correlation between blood stasis syndrome and non-blood stasis syndrome of lumbar intervertebral disc protrusion remains unclear.
OBJECTIVE:To construct serum protein pattern model for diagnosing blood stasis syndrome of lumbar intervertebral disc protrusion.
METHODS:A total of 180 cases were included in this study and divided into treatment group (120 patients with lumbar intervertebral disc protrusion) and control group (60 healthy cases from physical examination). Furthermore treatment group was equal y assigned into blood stasis syndrome subgroup and non-blood stasis syndrome subgroup, with 60 cases in each subgroup. The involved cases were wel matched in nations, genders and ages. Serum samples of peripheral blood from the 180 cases were col ected. Surface-enhanced laser desorption/inionation time of flight mass spectrometry and ProteinChip technology were employed to detect and plot protein mass spectrum. The protein peak values were identified using Biomarker Wizard software. Then serum diagnosis model of blood stasis syndrome of lumbar intervertebral disc protrusion was established. The obtained models were verified through double blind method. The differential proteins were searched by ExPASy data.
RESULTS AND CONCLUSION:We detected that peak values of eleven proteins had statistical significance (P<0.05) from the involved 180 cases. Among them, two proteins were highly expressed while the other nine proteins were lowly expressed. Serum protein pattern model for diagnosing blood stasis syndrome of lumbar intervertebral disc protrusion was established through Biomarker Patterns software, and the sensibility was 86.667%, the specificity was 94.167%, the positive predictive value was 88.136%. There are a variety of abnormal y expressed proteins in the serum of the patients with blood stasis syndrome of lumbar intervertebral disc protrusion. The serum protein pattern model involved eleven different proteins can be used to diagnose blood stasis syndrome of lumbar intervertebral disc protrusion.