1.Mechanical stress regulates apoptosis in vascular smooth muscle cells
Fei XU ; Jinqiang YAN ; Shoudong CHAI
Chinese Journal of Tissue Engineering Research 2025;29(5):1064-1072
BACKGROUND:With the development of biomechanics,its research into cardiovascular diseases has become more and more extensive.By studying the mechanical properties of blood vessels,the pathogenesis of cardiovascular diseases such as atherosclerosis and restenosis can be effectively revealed and new ideas and methods can be developed for the treatment of cardiovascular diseases. OBJECTIVE:To review the research status of apoptosis of vascular smooth muscle cells induced by mechanical stress and search for potential target molecules and signaling pathways for clinical treatment,thereby improving the clinical treatment effect on cardiovascular diseases such as atherosclerosis and restenosis. METHODS:We searched the literature in CNKI,PubMed and ScienceDirect databases from January 1992 to May 2023.The search terms were"vascular smooth muscle cell,mechanical stress,shear stress,stretch stress,apoptosis"in Chinese and English.Finally,63 articles were included for review and analysis. RESULTS AND CONCLUSION:Physiological and pathological apoptosis of vascular smooth muscle cells is an adaptive remodeling in response to the changes in vascular mechanics.Vascular smooth muscle cells in different parts have different mechanical stimuli and their pathogenesis is also different.Low shear stress,physiological shear stress and high shear stress directly interact with surface molecules,receptors and proteins of vascular smooth muscle cells to regulate apoptosis-related signaling molecules and inhibit cell proliferation,thus regulating the apoptosis of vascular smooth muscle cells.In this part,the research on promoting proliferation is not summarized.Low stretch stress,physiological stretch stress and high stretch stress can all cause apoptosis of vascular smooth muscle cells,but it is still controversial.There are many mechanoreceptors(such as integrins and receptor tyrosine kinases)on the surface of vascular smooth muscle cells,which can transform mechanical signals into intracellular chemical signals(such as the Hippo pathway),activate the apoptosis signals of vascular smooth muscle cells and regulate the apoptosis of vascular smooth muscle cells.In short,different mechanical stimuli start a variety of signal pathways and regulate the apoptosis of vascular smooth muscle cells through various signal molecules.For example,shear stress affects Fas/FasL and Akt pathways mainly by stimulating prostaglandin secretion and transforming growth factors.Strech stress mainly regulates the YAP pathway and Notch pathway through Yes-related proteins.At different times or intensities,these molecules may play opposite two-way roles.For example,when mouse vascular smooth muscle cells are stretched at 10%physiological tension for 1 hour,cell proliferation increases.However,the proliferation of human vascular smooth muscle cells can decrease after 12 hours of stretching.Clinically,the key molecules of mechanical transduction can be disturbed by searching for key molecules that interfere with mechanical transduction at their critical time points of action.
2.Decompression mechanism of symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous
Chunlin ZHANG ; Zhaohua HOU ; Xu YAN ; Yan JIANG ; Su FU ; Yongming NING ; Dongzhe LI ; Chao DONG ; Xiaokang LIU ; Yongkui WANG ; Zhengming CAO ; Tengyue YANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1810-1819
BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.
3.Pathogenesis and Syndrome Differentiation Treatment of Heart Failure Based on "Spleen-mitochondria" and Theory of "Dampness, Turbidity, Phlegm, and Fluid-related Diseases"
Rui ZHANG ; Fuyun JIA ; Jingshun YAN ; Xuan LIU ; Yadong WANG ; Yinan MA ; Yan LIU ; Qiang XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):265-274
Guided by Academician Zhang Boli's theory of "dampness, turbidity, phlegm, and fluid-related diseases",this paper elaborated on the pathogenesis and syndrome differentiation treatment of heart failure from the perspective of the "spleen-mitochondria". It analyzed the essential similarities between "spleen-mitochondria" and "dampness, turbidity, phlegm, and fluid-related diseases", as well as their close association with the onset of heart failure. Furthermore,it explored the connection between spleen function and mitochondrial function in traditional Chinese medicine (TCM),positing that the spleen's role in transportation and transformation is analogous to mitochondrial material metabolism and energy conversion,with spleen deficiency closely related to mitochondrial dysfunction. It thus concluded that mitochondrial material metabolism and energy conversion represent the microscopic essence of the spleen's role in transportation and transformation,and mitochondrial dysfunction is a contributing factor to pathological products like dampness and turbid phlegm,which are closely associated with the occurrence of heart failure. The four elements of dampness,turbidity,phlegm,and fluid are a series of related symptoms resulting from abnormal fluid transportation and transformation,serving as both factors in the onset of heart failure and the core pathological basis for its deterioration. Therefore,during the treatment of heart failure,it is essential to regulate mitochondrial function. Early intervention should focus on eliminating dampness and turbidity to improve mitochondrial function and restore normal energy metabolism. In the middle and late stages,emphasis should be placed on resolving phlegm,promoting blood circulation,warming Yang,and reducing water retention to alleviate mitochondrial damage and improve cardiac function. Supporting Qi and strengthening the spleen should be a continuous approach,and treatment should be adjusted to enhance mitochondrial function and stabilize the condition,thereby improving prognosis. This paper discussed the role of the spleen and mitochondria in the pathogenesis of heart failure,examined the evolution of heart failure mechanisms from the perspective of dampness, turbidity, phlegm, and fluid-related diseases,and proposed a phased treatment strategy. It enriched the theory of dampness, turbidity, phlegm, and fluid-related diseases and offered new strategies for heart failure treatment. However,in practical application,TCM strategies for treating heart failure need to be integrated with modern medical approaches to provide a more solid scientific foundation for treatment.
4.Analysis of characteristics of adverse drug reactions in a hospital from 2021 to 2023
Yan WANG ; Ming FANG ; Hongwei SONG ; Chao ZHONG ; Feng XU ; Ting ZHOU
Journal of Pharmaceutical Practice and Service 2025;43(4):200-204
Objective To analyze the characteristics of adverse drug reactions (ADR) reported in Sixth People’s Hospital South Campus, Shanghai Jiaotong University from 2021 to 2023, to provide reference for promoting rational clinical drug use. Methods ADR data reported in our hospital were collected retrospectively, including patients’ basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data. Results A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients (63.5%). The top five drugs involved with adverse reactions were antibiotics (48.8%), Chinese medicine injections(19.2%), vitamins(7.5%), Chinese traditional medicine(7.2%), equine tetanus immunoglobulin(6.3%). Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage (55.4%). The clinical manifestations were rash, itching, and maculopapular rash. Conclusion From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital were mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be concerned.
5.Effects of intravenous and intraperitoneal routes on Babesia microti infections and splenic immune cells in BALB/c mice
Hanyin YANG ; Yuchun CAI ; Shuning YAN ; Yi XIN ; Ziran MO ; Bin XU ; Bin ZHENG
Chinese Journal of Schistosomiasis Control 2025;37(1):61-68
Objective To investigate the changes in the prevalence of Babesia microti infections, spleen morphology and proportions of splenic immune cells in BALB/c mice following intravenous and intraperitoneal injections, so as to provide insights into unraveling the immune regulatory mechanisms of Babesia infections. Methods Laboratory - maintained B. microti strains were prepared into whole blood samples with 10% prevalence of B. microti infection. A total of 75 BALB/c mice were randomly divided into three groups, including the normal control group, intravenous injection group, and intraperitoneal injection group, of 25 mice in each group. Mice in the intravenous and intraperitoneal injection groups were administered 100 μL of whole blood samples with 10% prevalence of B. microti infection, with the day of injection recorded as d0, and animals in the normal control group were given no treatments. Blood was sampled from mice in each group via the tail tip on d7, d14, d21, d28 and d35, and prepared into thin-film blood smears, and B. microti infection was observed in red blood cells. Five mice were randomly sampled from each group and sacrificed on d7, d14, d21, d28 and d35, and spleen was collected for measurement of spleen size and weight. In addition, splenic cells were isolated, and the proportions of CD3e+ T cells, CD45R+ B cells, CD49b+ nature killer (NK) cells, and F4/80+ macrophages were detected in CD45+ lymphocytes using flow cytometry. Results The prevalence of B. microti infection in the intravenous (22.80%) and intraperitoneal injection groups (44.82%) peaked on d7 (χ2 = 8.141, P < 0.01) and then rapidly decreased, and no parasites were observed on d35. The longest mouse spleen length [(32.91 ± 2.20) mm] and width [(9.82 ± 0.43) mm], and the greatest weight [(0.78 ± 0.10) g] were found on d14 in the intravenous injection group, and the longest spleen length [(32.42 ± 3.21) mm] and width [(10.25 ± 0.73) mm], and the greatest weight [(0.73 ± 0.09) g] were seen in the intra-peritoneal injection group on d21, d7 and d14, respectively. There were significant differences among the intravenous injection group, intraperitoneal injection group and the normal control group in terms of spleen length (F = 10.310, P < 0.05), width (F = 9.824, P < 0.05), and weight (F = 10.672, P < 0.05) on d21, and the mouse spleen length, width and weight were all significantly greater in the intraperitoneal injection group than in the intravenous injection group (allP values < 0.05). The proportions of splenic CD3e+ T cells [(60.60 ± 6.20)% and (39.68 ± 7.62)%], CD45R+ B cells [(43.32 ± 2.08)% and (49.53 ± 4.90)%], CD49b+ NK cells [(6.88 ± 1.34)% and (7.71 ± 1.59)%], and F4/80+ macrophages [(2.21 ± 0.29)% and (3.80 ± 0.35)%] peaked on d14, d21, d21 and d14 in the intravenous and intraperitoneal injection groups, respectively. There were significant differences in the proportions of CD3e+ T cells (F = 16.730, P < 0.05) and F4/80+ macrophages (F = 15.941, P < 0.05) among the intravenous injection group, intraperitoneal injection group and normal control group on d14, and a higher proportion of CD3e+ T cells and a lower proportion of F4/80+ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (both P values < 0.01). There were significant differences among the intravenous injection group, intraperitoneal injection group and normal control group on d21 in terms of proportions of splenic CD3e+ T cells (F = 9.252, P < 0.05), CD45R+ B cells (F = 14.349, P < 0.05), CD49b+ NK cells (F = 13.436,P < 0.05), and F4/80+ macrophages (F = 8.180, P < 0.05), and a higher proportion of CD3e+ T cells and lower proportions of CD45R+ B cells and F4/80+ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (all P values < 0.01). In addition, there was a significant difference in the proportion of CD3e+ T cells among the intravenous injection group, intraperitoneal injection group and normal control group on d28 (F = 9.772,P < 0.05), and a lower proportion of CD3e+ T cells was found in the intravenous injection group than in the intraperitoneal injection group (P < 0.01). Conclusions Both intraperitoneal and intravenous routes are effective to induce B. microti infections in BALB/c mice, and the prevalence of B. microti infections is higher in BALB/c mice through the intraperitoneal route than through the intravenous route. Intraperitoneal and intravenous injections with B. microti cause diverse spleen morphologies and proportions of splenic immune cells in mice, indicating routes of B. microti infections cause different impacts on immune response mechanisms in mice.
6.Trend and influencing factors of low birth weight among newborns in Chongming District of Shanghai from 2008 to 2022
Aiyu SHI ; Tianyi GU ; Yan XU ; Yuhua HUANG ; Xiaolei SUN
Shanghai Journal of Preventive Medicine 2025;37(2):168-173
ObjectiveTo analyze the trend and influencing factors of low birth weight (LBW) among newborns in Chongming District of Shanghai from 2008 to 2022, so as to provide references for the development of intervention measures reducing the rate of LBW. MethodsBirth surveillance data of Chongming District of Shanghai from 2008 to 2022 were collected and organized, and the annual percentage change (APC) of LBW was calculated by using Joinpoint 5.0.2 software for trend change analysis. Logistic regression analysis was used to analyze the influencing factors of LBW. ResultsThe overall incidence of LBW was 3.71% in Chongming District, Shanghai from 2008 to 2022. Joinpoint trend analysis showed that the incidence of LBW in Chongming District had an upward trend (APC=5.49%, 95%CI: 3.31%‒7.72%, P<0.001).Multivariate logistic regression analysis showed that preterm birth, multiple births, female infants, birth defects, first pregnancy, primiparity, and a young father age (<20 years) were risk factors for LBW in Chongming District. Among the term infants, female infants, birth defects, and first pregnancy were risk factors for LBW (P<0.05). Female infants, birth defects, first pregnancy, primiparity, advanced maternal age (≥35 years), and a young father age (<20 years) were risk factors in singleton neonates. ConclusionThe incidence of LBW among newborns is on the rise in Chongming District of Shanghai. Therefore, high risk groups need to be identified, and prenatal check-ups and pregnancy care should be strengthened to reduce the risk of neonatal LBW.
7.Clinical observation of enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion for postoperative hepatocellular carcinoma resection
Ming ZHANG ; Huaying YAN ; Dongping XU ; Jingjing WANG ; Licheng ZHANG ; Yumei QI
China Pharmacy 2025;36(8):961-965
OBJECTIVE To study the effects of enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion on postoperative recovery, immune function, liver function and inflammation level in patients with hepatocellular carcinoma resection, as well as the safety of the medication. METHODS A total of 106 patients with hepatocellular carcinoma admitted to our Hospital from June 2020 to December 2023 were selected and divided into control group and study group according to the random number table method, with 53 cases in each group. After undergoing hepatocellular carcinoma resection, control group was given Intacted protein enteral nutrition solution+Enhanced enteral immune microecological nutrition, and the study group was given ω-3 fish oil fat emulsion injection based on the control group. The clinical indicators (postoperative exhaust time, defecation time, postoperative ambulation, and hospital stay), liver function indicators [alanine transaminase (ALT), lactate dehydrogenase (LDH), aspartate transaminase (AST)], immune function indexes (CD3+ , CD4+ , CD8+ , CD4+/CD8+), inflammatory factor indexes [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8], and indicators of intestinal mucosal barrier [D-lactic acid, intestinal fatty acid binding protein (I-FABP)] were compared between 2 groups, and the occurrence of ADR was recorded. RESULTS Compared with the control group, the postoperative exhaust time, postoperative defecation time, and hospital stay of the study group were shortened significantly, and postoperative ambulation increased significantly (P<0.05). After treatment, ALT, LDH, AST, CD8+, inflammatory factors, D-lactic acid and I-FABP of 2 groups were significantly lower than before treatment, and the study group was significantly lower than the control group (P<0.05); CD4+, CD3+, and CD4+/CD8+ of two groups were significantly higher than before treatment, and the study group was significantly higher than the control group (P<0.05). There was no significant difference in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS Enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion injection can shorten the recovery time of patients after hepatocellular carcinoma resection, improve immune function, reduce inflammatory response, and improve liver function with good safety.
8.Research progress on the improvement of myocardial fibrosis by traditional Chinese medicine through regulation of NLRP3 inflammasome
Rui ZHANG ; Jingshun YAN ; Fuyun JIA ; Kexin JIA ; Chenyang LIU ; Yan LIU ; Ye LI ; Qiang XU
China Pharmacy 2025;36(8):1008-1012
Myocardial fibrosis (MF), characterized by decreased cardiac function and myocardial compliance, is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine (TCM) can regulate the NLRP3 inflammasome to alleviate MF. Based on this, this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM, such as alkaloids (lycorine,vincristine,bufalin), saponins (astragaloside Ⅳ, diosgenin,ginsenoside Rg3), terpenoids (celastrol,oridonin), and phenols (polydatin,curcumin,phloridzin) as well as TCM formulas (Zhachong shisanwei pills,Zhilong huoxue tongyu capsules, Luqi formula) can inhibit the activation of the NLRP3 inflammasome, thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18, reducing inflammatory damage to myocardial tissue, alleviating excessive deposition of the extracellular matrix, and thus exerting the effect of improving MF.
9.Establishment of a nomogram prediction model for poor prognosis of acute pancreatitis based on inflammatory factors, lung ultrasound, and CT scores
Xia REN ; Ye YE ; Luojie LIU ; Xiaodan XU ; Yan ZHANG
Journal of Clinical Hepatology 2025;41(4):713-721
ObjectiveTo investigate the independent risk factors for poor prognosis in patients with acute pancreatitis (AP) by analyzing inflammatory factors, lung ultrasound (LUS) scores, and CT scores, to establish a nomogram prediction model, and to provide a basis for early clinical intervention. MethodsA total of 409 patients with AP who were admitted to Changshu Hospital Affiliated to Soochow University from January 2021 to October 2023 were enrolled as subjects, and they were divided into modeling group with 288 patients and validation group with 121 patients using the simple random sampling method at a ratio of 7∶3. According to the prognosis, each group was further divided into poor prognosis group and good prognosis group. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were measured for both groups within 72 hours after admission, and LUS scores, modified CT severity index (MCTSI), and extrapancreatic inflammation on computed tomography (EPIC) scores were assessed within 48 — 72 hours after admission. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A LASSO regression analysis was used to screen for the variables that were included in the multivariate logistic regression model to identify the independent risk factors for the poor prognosis of AP, and then a nomogram prediction model was established. The receiver operating characteristic (ROC) curve and the calibration curve were used to assess the discriminatory ability and goodness of fit of the nomogram model, and a decision curve analysis was used to assess the clinical applicability of the model. ResultsAmong the 288 patients with AP in the modeling group, there were 33 (11.46%) in the poor prognosis group and 255 (88.54%) in the good prognosis group; among the 121 patients with AP in the validation group, there were 13 (10.74%) in the poor prognosis group and 108 (89.26%) in the good prognosis group. Compared with the good prognosis group, the poor prognosis group had significantly higher levels of CRP (Z=3.607, P<0.05), IL-6 (Z=4.189, P<0.05), and TNF-α (t=2.584, P<0.05), and significantly higher scores of LUS (t=8.075, P<0.05), MCTSI (t=5.929, P<0.05), and EPIC (t=8.626, P<0.05). The multivariate logistic regression analysis showed that CRP (odds ratio [OR]=3.592, 95% confidence interval [CI]: 1.272 — 10.138, P<0.05), IL-6 (OR=4.225, 95%CI: 1.468 — 12.156, P<0.05), TNF-α (OR=3.540, 95%CI: 1.205 — 10.401, P<0.05), LUS (OR=7.094, 95%CI: 2.398 — 20.986, P<0.05), MCTSI (OR=7.612, 95%CI: 2.832 — 20.462, P<0.05), and EPIC (OR=11.915, 95%CI: 4.007 — 35.432, P<0.05) were independent risk factor for poor prognosis in patients with AP. A nomogram prediction model was established based on the above 6 indicators, which had an area under the ROC curve of 0.924 (95%CI: 0.883 — 0.964), and the Youden index for the optimal cut-off value was 0.670, with a sensitivity of 0.909 and a specificity of 0.761. The calibration curve showed good consistency between the predicted and observed results in both the modeling group and the validation group. The decision curve analysis showed that the predictive model had certain clinical effectiveness. ConclusionThe nomogram model for predicting the risk of poor prognosis in AP patients based on CRP, IL-6, TNF-α, LUS score, MCTSI score, and EPIC score has relatively good predictive performance and can provide important strategic guidance for developing early intensified treatment regimens for AP patients in clinical practice.
10.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

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