1.Role of insulin-like growth factor-Ⅰ in prognostic evaluation and treatment of liver cirrhosis
Yanping WANG ; Ya ZHENG ; Huifang ZHANG ; Huimin WANG ; Xiaotong MA ; Zhaofeng CHEN
Journal of Clinical Hepatology 2025;41(6):1188-1193
As a key member of the insulin-like growth factor family, insulin-like growth factor-Ⅰ (IGF-Ⅰ) is mainly synthesized in the liver and is widely distributed in the human body, and it is involved in the physiological processes such as cell proliferation, differentiation, metabolism, and apoptosis. Studies have shown that the level of IGF-Ⅰ is negatively correlated with the severity of liver cirrhosis, and IGF-Ⅰ mainly affects the progression of liver cirrhosis by inhibiting liver fibrosis, promoting DNA damage repair, and regulating lipid metabolism. Monitoring of IGF-Ⅰ level is expected to provide an evaluation indicator for improving the prognosis of patients with liver cirrhosis, and stimulating the action pathway of IGF-Ⅰ or regulating its expression level may become a new method for the treatment of liver cirrhosis. This article reviews the research advances in IGF-Ⅰ in liver cirrhosis, in order to provide new ideas for the diagnosis and treatment of liver cirrhosis.
2.Efficacy and safety of camrelizumab combined with apatinib in the treatment of triple-negative breast cancer:a Meta-analysis and systematic review
Zhaofeng NIU ; Yanghai ZHAI ; Rui GENG
Chinese Journal of Pharmacoepidemiology 2024;33(10):1137-1146
Objective To systematically review the efficacy and safety of camrelizumab and apatinib in the treatment of triple-negative breast cancer.Methods PubMed,Web of Science,Embase,Cochrane Library,CNKI,and WanFang Data databases were electronically searched to collect clinical studies of carelizumab combined with apatinib(combination group)or it vs.carelizumab alone(single group)in the treatment of triple-negative breast cancer from inception to June 14,2024.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias in the included studies.Meta-analysis was performed by using RevMan 5.4.1 and STATA 15 softwares.Results A total of 6 studies were included,1 randomized controlled trial,2 cohort studies,and 3 single-arm trials,involving 366 patients.The results of the Meta-analysis indicated that the objective response rate(ORR)(OR=2.77,95%CI 1.60 to 4.81,P<0.001),and disease control rate(DCR)(OR=2.27,95%CI 1.34 to 3.85,P=0.002)in the combination group were significantly higher than those of the single group.The results of the single-arm trial showed that after the treatment of camrelizumab combined with apatinib,the ORR and DCR of the patients were 28%(95%CI 0.04 to 0.52)and 65%(95%CI 0.37 to 0.92),respectively.The overall progression-free survival of the patients after the combined treatment was 5.66 months(95%CI 3.78 to 8.48).The incidences of leukopenia(OR=1.45,95%CI 0.50 to 4.17,P=0.49),rash(OR=1.11,95%CI 0.35 to 3.49,P=0.86),nausea and vomiting(OR=1.28,95%CI 0.36 to 4.61,P=0.70)were not statistically significantly between the combination group and the single group.Conclusion Current evidence shows that carilizumab combined with apatinib has synergistic efficacy in treating triple-negative breast cancer,improves cellular immune function,and has a controllable safety profile.Due to the limitations of the number and quality of studies included,the above conclusion still needs to be verified by more high-quality studies.
3.Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis
Miao LI ; Jiacong XIAO ; Baihao CHEN ; Zhaofeng PAN ; Fanchen WANG ; Weijian CHEN ; Qi HE ; Jianliang LI ; Shaocong LI ; Ting WANG ; Gangyu ZHANG ; Haibin WANG ; Jianfa CHEN
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):977-990
Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.
4.Effect and mechanism of ammonium pyrrolidine dithiocarbamate on neuroinflammation in rats with traumatic brain injury
Jiafa YANG ; Zhaofeng LU ; Yaqiong WANG ; Ruoyu LU ; Hairong LI ; Mengjia LIU
Journal of Xinxiang Medical College 2024;41(7):631-639
Objective To investigate the effect and mechanism of ammonium pyrrolidine dithiocarbamate(PDTC)on neuroinflammatory injury in the penumbra of traumatic brain injury(TBI)in rats.Methods Sixty Sprague Dawley rats were divided into the PDTC group,TBI group,sham operation group and control group according to the random number table method,with 15 rats in each group.Rats in the PDTC group were intraperitoneally injected with PDTC(100 mg·kg-1)at 15 minutes before surgery;while the rats in the TBI group,sham operation group,and control group were intraperitoneally injected with the same volume of double distilled water.After the cranial window of rats in the TBI group and PDTC group was created,a 2.5 g steel rod with an inner diameter of 6.0 mm was dropped freely from a height of 75 cm through a transparent polyvinyl chloride tube with an inner diameter of 7.0 mm to impact the dura mater and induce right parietal lobe contusion and laceration to establish the TBI model;rats in the sham operation group were sealed with bone wax after the cranial window creation,without any impact applied;rats in the control group were raised under normal conditions.The modified neurological severity score(mNSS)was used to evaluate the degree of neurobehavioral damage in rats in each group at 1,4 and 7 days after modeling.At 2 days after modeling,5 rats in each group were decapitated,and brain tissues were taken for hematoxylin & eosin(HE)staining,and morphological changes of the brain tissues were observed under an optical microscope.The expressions of β-amyloid precursor protein(β-APP)and glial fibrillary acidic protein(GFAP)in the brain tissues of rats in each group were detected by immunohistochemical staining.At 24 hours after modeling,5 rats in each group were decapitated,and the right injured penumbra tissues were obtained;the expressions of nuclear transcription factor-κB(NF-κB)P65,phosphorylated NF-κB P65,inhibitor of NF-κB(IκB),phosphorylated IKB,NOD-like receptor protein 3(NLRP3)and caspase-1 protein in the right injured penumbra tissue of rats in each group were detected by Western blot,and the expressions of NF-κB P65,IκB,NLRP3 and caspase-1 mRNA in the right injured penumbra tissue of rats in each group were determined by real-time quantitative polymerase chain reaction.Results At 1,4,and 7 days after modeling,the mNSS scores of rats in the TBI group were signifi-cantly higher than those in the PDTC group,control group and sham operation group.The mNSS scores of rats in the PDTC group were significantly higher than those in the control group and sham operation group(P<0.05);there was no statistically significant difference in mNSS scores between the sham operation group and the control group(P>0.05).The neurons and neurogliocyte of rats in the control group and the sham operation group exhibited normal morphology,without swelling and wide-ning of intercellular space.Diffuse hemorrhagic changes were observed in the brain tissues of rats in the TBI group,with different morphologies of neuronal cell body,unclear cell membrane and cytoplasm,pyknosis of cell nuclei,often triangular shape,disappearance of normal structure and nucleoli,and diffuse white blood cells and red blood cells filling the field of vision.The lesion surrounding area of rats in the PDTC group showed ischemic changes,with mild shrinkage of neuronal volume,a uniform light red color,karyopyknosis,nuclear-cytoplasmic dissociation,disappearance of normal structure and nucleoli,and localization of neuroinflammation.There was no significant expression of β-APP and GFAP in the cerebral cortex of rats in the control group and the sham operation group,while the accumulation of β-APP and GFAP in neuronal serosae and/or axons was observed in the brain tissues of rats in the TBI group and the PDTC group.Compared with the TBI group,a decrease in the number and the expression intensity of β-APP and GFAP-positive stained neuronal cells in the cerebral cortex of rats was observed in the PDTC group.The relative expression of NF-κB P65 protein in the brain tissues of rats in the sham operation group,TBI group and PDTC group was significantly higher than that in the control group,and the relative expression of NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P<0.05).The relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group and the sham operation group was significantly lower than that in the control group,the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group and the sham operation group,and the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly lower than that in both TBI group and sham operation group(P<0.05).There was no significant difference in the relative expression of IκB protein in the brain tissues of rats between the sham operation group and the control group(P>0.05);the relative expression of IκB protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group,and the relative expression of IκB protein in the brain tissues of rats in the PDTC group was significantly lower than that in the control group,sham operation group,and TBI group(P<0.05).The relative expression of phosphorylated IκB protein in the brain tissues of rats in the TBI group was significantly lower than that in the control group and the sham operation group,and the relative expression of phosphorylated IκB protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P<0.05).The relative expression of NLRP3 protein in the brain tissues of rats in the sham opera-tion group was significantly higher than that in the control group,the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group and the PDTC group was significantly lower than that in the sham operation group and the control group,and the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group was significantly lower than that in the PDTC group(P<0.05).The relative expression of caspase-1 protein in the brain tissues of rats in the sham opera-tion group,PDTC group,and TBI group was significantly higher than that in the control group,and the relative expression of caspase-1 protein in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group,TBI group,and sham operation group was significantly higher than that in the control group,the relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expres-sion of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of IκB mRNA in the brain tissues of rats in the PDTC group and TBI group were signifi-cantly higher than that in the control group,and the expression of IκB mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group(P<0.05).The relative expression of IκB mRNA in the brain tis-sues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of IκB mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P<0.05).The relative expression of caspase-1 mRNA in the brain tissues of rats in the sham operation group,TBI group,and PDTC group was significantly lower than that in the control group,the relative expression of caspase-1 mRNA in the brain tissues of rats in the TBI group and PDTC group was significantly higher than that in the sham operation group(P<0.05).Conclusion PDTC can effectively improve neural functional deficit score and reduce neuroinflammatory injury in TBI rats,the mechanism of which may be related to regulating mRNA and protein expression of NF-κB/NLRP3 axis-related inflammatory injury indicators and regulating downstream inflammatory factors.
5.Application Progress of Cardiovascular Magnetic Resonance in the Evaluation of Cancer Treatment-Related Cardiovascular Disease
Zhaofeng FENG ; Shuhao LI ; Haibo REN ; Lianggeng GONG
Chinese Journal of Medical Imaging 2024;32(7):736-740,746
With the development of cancer treatment,patient survival rates have substantially improved.But cancer therapies may come along with potential cardiotoxic effects resulting in cardiovascular disease with increased morbidity and mortality.Ultimately,patients may survive their malignancy but die as a result of cancer treatment.It is crucial that being able to identify cardiovascular damage early and develop strategies that may ameliorate the damage secondary.Cardiovascular magnetic resonance imaging can provide a"one-stop"assessment of cardiac architecture,cardiac function,myocardial tissue characteristics,and cardiac macrovascular hemodynamics,and it is useful in assessing cardiovascular injury,particularly early injury.The objective of this review is to review the application and progress of various cardiovascular magnetic resonance imaging methods in the evaluation of cancer treatment-related cardiovascular disease.
6.An insight into the mechanism of iron overload in knee osteoarthritis under the theory of blood stasis
Jiaxu ZENG ; Qi HE ; Bohao CHEN ; Miao LI ; Shaocong LI ; Junzheng YANG ; Zhaofeng PAN ; Haibin WANG
Chinese Journal of Tissue Engineering Research 2024;28(11):1743-1748
BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.
7.Risk factors of postoperative mortality of femoral neck fractures in elderly patients and construction of a nomogram predictive model
Zhipeng LI ; Dawei HUAN ; Zhaofeng YUAN ; Yue QIU ; Chao ZHANG ; Tianwei XIA ; Jirong SHEN
Chinese Journal of Tissue Engineering Research 2024;28(21):3361-3366
BACKGROUND:With a gradually aging population,improving the ability to screen for the risk of death after arthroplasty and implementing timely personalized intervention programs for the increasing number of elderly patients with femoral neck fractures is key to improving the postoperative status of patients and prolonging survival expectations. OBJECTIVE:To investigate the risk factors for postoperative mortality in elderly patients with femoral neck fractures and to construct a nomogram predictive model to predict their mortality risk. METHODS:The study was conducted on 155 elderly patients(≥65 years old)who underwent arthroplasty for femoral neck fracture from January 2016 to January 2021,and 147 patients who met the inclusion criteria were analyzed to collect clinical data that may affect the patients'postoperative mortality.Single-factor and multi-factor Cox regression analyses were successively used to screen independent risk factors associated with postoperative mortality.The column line graph model was constructed and validated using Rstudio software. RESULTS AND CONCLUSION:(1)Age,frailty(age-adjusted Charlson comorbidities score),preoperative activity status,osteoporosis,and postoperative serum albumin level were five independent risk factors for postoperative mortality in elderly patients with femoral neck fractures(P<0.05).(2)The nomogram predictive model was constructed based on the results of multifactorial analysis,with a consistency index of 0.819(95%CI:0.771-0.868).Receiver operating characteristic curve analysis showed that the area under curve for 1-year and 3-year survival prediction was 0.8543 and 0.7263,respectively,indicating that the nomogram predictive model has good discriminatory and predictive power;calibration curve and decision curve analysis also showed good model discriminative power and clinical utility value.(3)The constructed nomogram predictive model has good diagnostic efficacy and accuracy,and can effectively assess the risk of postoperative death of patients.
8.Mid-and long-term state after total hip arthroplasty versus hemiarthroplasty for femoral neck fractures in the elderly:evaluation using propensity score matching method
Zhipeng LI ; Dawei HUAN ; Zhaofeng YUAN ; Kai DING ; Yue QIU ; Tianwei XIA ; Jirong SHEN
Chinese Journal of Tissue Engineering Research 2024;28(24):3839-3844
BACKGROUND:Arthroplasty is the primary treatment for displaced femoral neck fractures in the elderly,and the choice of total hip arthroplasty versus hemiarthroplasty is currently the subject of considerable debate. OBJECTIVE:To compare the mid-and long-term survival status of total hip arthroplasty versus hemiarthroplasty under a direct anterior approach for displaced femoral neck fractures in the elderly based on the propensity score matching method. METHODS:One hundred and forty-seven elderly patients(≥65 years of age)with displaced femoral neck fractures were admitted from January 2016 to January 2021,of whom 88 had total hip arthroplasty(total hip arthroplasty group)and 59 had artificial femoral head replacement(hemiarthroplasty group).For the patients'preoperative comorbidities,the age-corrected Charlson Comorbidity Scale was used to quantify the scores and calculate patient frailty.The propensity score matching method was used to match the two groups 1:1 and to compare the operation time,bleeding,postoperative hospitalization time,hospitalization cost,nutritional index,postoperative complications,and mortality between the two groups after matching.Postoperative survival time was determined by Kaplan-Meier Survival analysis. RESULTS AND CONCLUSION:(1)After propensity score matching,a total of 42 matched pairs were successful in both groups,and the preoperative data of patients in both groups were balanced and comparable after matching(P>0.05).(2)Compared with the hemiarthroplasty group,operation time(79.71 minutes vs.59.07 minutes,P<0.001),bleeding volume(839.64 mL vs.597.83 mL,P=0.001),and hospitalization cost(56 508.15 yuan vs.41 702.85 yuan,P<0.001)were significantly higher in the total hip arthroplasty group.However,the mortality rate was lower in the total hip arthroplasty group than in the hemiarthroplasty group(36%vs.57%,HR=0.44,95%CI:0.23-0.87,P=0.018),and the mean survival time was longer in the total hip arthroplasty group than in the hemiarthroplasty group(59.4 months vs.43.7 months,P=0.024).(3)There were no statistically significant differences in postoperative hospitalization time,preoperative and postoperative nutritional indicators,and overall postoperative complication rate between the two groups(P>0.05).However,in terms of postoperative pain,the incidence of pain was significantly higher in the hemiarthroplasty group than that in the total hip arthroplasty group(24%vs.7%,P=0.035).(4)Overall,total hip arthroplasty has a better prognosis for survival,while hemiarthroplasty is more appropriate for patients with poor physical fitness.At the same time,postoperative pain may largely affect the quality and survival time of patients after hip arthroplasty.
9.Regulation of Local Immunoglobulin Expression by MZB1 in Chronic Rhinosinusitis with Nasal Polyps
Yan YAN ; Zhaofeng XU ; Yanran HUANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):383-392
[Objective]The heightened expression of local immunoglobulins is a significant pathological characteristic of chronic rhinosinusitis with nasal polyps(CRSwNP),particularly in the Asian population.This study is centered on ex-ploring the association between MZB1 and the localized aggregation of immunoglobulins in Asian individuals with CRSwNP.[Methods]Nasal polyp tissues obtained from 40 CRSwNP patients and inferior turbinates from 6 healthy controls under-went examination for both mRNA and protein levels.The assessments were conducted using polymerase chain reaction,lu-minex,and immunohistochemical staining.Statistical analyses,including one-way Anova(ANOVA),independent sam-ples t-test,and Pearson's correlation analysis,were employed for comprehensive data evaluation.[Results]The mRNA ex-pression levels of MZB1(P<0.01)and HSP90B1(P<0.01)were significantly higher in type 2 CRSwNP patients com-pared with those in healthy controls.Immunohistochemical staining revealed a significant increase in MZB1 protein expres-sion in type 2 CRSwNP.MZB1 demonstrated correlation with the expression of immunoglobulin E in nasal polyp tissues(P<0.01,r=0.52).Additionally,MZB1correlated with the expression ofIL-5(P<0.05,r=0.4)and IL-13(P<0.05,r=0.44)in nasal polyp tissues.Furthermore,MZB1showed correlation with the number of eosinophils in nasal polyp tis-sues(P<0.05,r=0.72).[Conclusion]The expression of MZB1 is notably elevated in Asian CRSwNP,particularly in type 2 CRSwNP,when compared with controls.MZB1expression correlates significantly with high IgE expression and dis-ease severity in nasal polyp tissues.
10.Establishment and Validation of A Prediction Model for the Occurrence of Acute Kidney Disease in Patients with Liver Cirrhosis
Jing OUYANG ; Hong CHANG ; Mengjiao YANG ; Meng ZHANG ; Meng TIAN ; Ya ZHENG ; Yuping WANG ; Zhaofeng CHEN
Medical Journal of Peking Union Medical College Hospital 2024;15(1):89-98

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