1.Effect of Guiqi Yiyuan Ointment on Lewis Lung Cancer Mice by Increasing Autophagic Flux and Stabilizing PD-L1 Expression Through Regulation of ERK Signaling Pathway
Nan YANG ; Qiangping MA ; Jianqing LIANG ; Kejun MIAO ; Shang LI ; Jintian LI ; Juan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):107-114
ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase (ERK) signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group, the model mice were randomly divided into the model group, Guiqi Yiyuan ointment low, medium, and high dose groups, and the extracellular ERK1/2 inhibitor group, with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75, 3.5, 7.0 g·kg-1·d-1 for the low, medium, and high dose groups, respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 (100 mg·kg-1·d-1) by gavage. The treatment was administered for 14 consecutive days, after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin (HE) staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 (p-ERK1/2) and the expression of programmed cell death ligand-1 (PD-L1) in tumor tissues. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of p-ERK1/2, PD-L1, the autophagy marker Beclin-1, the autophagic protein p62, and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group, the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment (P<0.05), and markedly reduced in the high dose and inhibitor groups (P<0.01). Tumor cells in all treatment groups became progressively irregular, with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased, and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment (P<0.05), and significantly reduced in the high dose and inhibitor groups (P<0.01). The mRNA expression of ERK1/2, PD-L1, Beclin-1, and p62 was reduced in the medium dose group (P<0.05), while LC3Ⅰ/Ⅱ mRNA expression was elevated (P<0.05). In the high dose and inhibitor groups, mRNA expression of ERK1/2, PD-L1, Beclin-1, and p62 was significantly reduced (P<0.01), while LC3Ⅰ/Ⅱ mRNA expression was significantly increased (P<0.01). Protein expression of p-ERK1/2, PD-L1, Beclin-1, and p62 was reduced in the medium dose group (P<0.05), and LC3Ⅰ/Ⅱ protein expression was elevated (P<0.05). In the high dose and inhibitor groups, protein expression of p-ERK1/2, PD-L1, Beclin-1, and p62 was significantly reduced (P<0.01), while LC3Ⅰ/Ⅱ protein expression was significantly elevated (P<0.01). ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway, downregulate the expression of p-ERK1/2, promote autophagic flux in tumor cells, and regulate the expression of PD-L1, thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.
2.Multi-center clinical study on the efficacy and safety of combined lienal polypeptide injection therapy in children with Mycoplasma pneumoniae pneumonia
Qi CHENG ; Yunxiao SHANG ; Han ZHANG ; Jiujun LI ; Ning CHEN ; Lishen SHAN ; Nan YANG ; Lihua NING ; Xuemei BAI ; Jianhua LIU ; Yuling HAN ; Jichun WANG ; Jing LI ; Yong FENG ; Liyun LIU ; Li CHEN ; Si LIU ; Qinzhen ZHANG ; Jia ZHENG ; Fengchao LI ; Sukun LU ; Yun ZHANG ; Xiaoyi CHAI
International Journal of Pediatrics 2025;52(3):204-210
Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized,controlled,multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1,2023 to January 31,2024 were included.According to the severity of pneumonia,they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP(SMPP/RMPP)group with 160 cases,and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1,using the random number table method.After screening,subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin,while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT,length of hospital stay,duration of fever,cough score,whether mild cases developed into severe or refractory cases,duration of hormone use,use of intravenous immunoglobulin(IVIG),bronchoscopy treatment,and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication,vital signs,blood routine,urine routine,liver function,myocardial enzymes,renal function,and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals,including 118 cases in the experimental group and 113 cases in the control group.Main observation index:the rate of lung CT aggravation in the experimental group was lower than that in the control group(2.6% vs 15.3%, P<0.01),and the difference was statistically significant.Secondary indexes:there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).However,the rate of cases of plastic bronchitis(PB)found under bronchoscopy in the experimental group was lower than that in the control group(0 vs 18.8%, P=0.03),and the difference was statistically significant.Among the mild MPP(72 cases),there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and the improvement rate of lung CT between the two groups(all P>0.05).However,compared with the control group,the rate of cases developing into SMPP/RMPP in the experimental group was less(24.3% vs 48.6%, P=0.03),and the difference in IgG before and after treatment was small[0.53(-0.04,1.18)g/L vs 1.33(0.48,2.25)g/L, P=0.01].Among the SMPP/RMPP cases(159 cases),the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group(0 vs 20%, P=0.04),and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group(1.3% vs 19.5%, P<0.01),and the improvement rate of lung CT in the experimental group was higher than that in the control group(88.8% vs 75.3%, P=0.03),with statistically significant differences.There were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).Two cases in the experimental group developed rashes,which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine,liver function,myocardial enzymes,renal function,electrocardiogram,and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP,reduce the rate of aggravation of the image findings,promote the absorption of lung inflammation,reduce the rate of PB found under bronchoscopy,and has good safety.
3.Dynamic ultrasound combined with 3.0T MRI for diagnosing and typing of synovial plica of knee joint
Nan LI ; Zhili WANG ; Danfeng XU ; Yan JIAO ; Ruisong SHANG
Chinese Journal of Medical Imaging Technology 2024;40(2):275-279
Objective To explore the value of dynamic ultrasound combined with 3.0T MRI for diagnosing and typing synovial plica of knee joint.Methods Dynamic ultrasound and 3.0T MRI data of 100 patients with suspected synovial plica of knee joint were retrospectively analyzed.Taking the results of arthroscopy as standards,the efficacy of dynamic ultrasound and 3.0T MRI alone and their combination for diagnosing synovial plica of knee joint were evaluated and compared.The length and thickness of synovial plica of knee joint measured with dynamic ultrasound,3.0T MRI alone and their combination were compared with those of arthroscopy,and the consistencies of the location and classification of synovial plica of knee joint with arthroscopy were analyzed.Results Synovial plica was detected in 70 cases,including 11 cases of supropatellar synovial plica,15 cases of infrapatellar synovial plica,medial patellar in 30 cases and lateral patellar synovial plica in 14 cases,among them type A,B,C and D were classified in 9,35,23 and 3 cases,respectively.No significant difference of sensitivity was found between dynamic ultrasound and 3.0T MRI alone for diagnosing synovial plica of knee joint(P>0.05),which were both lower than that of their combination(both P<0.05).The length and thickness of knee synovial plica measured with dynamic ultrasound and 3.0T MRI alone were lower than those measured with their combination and arthroscopy(all P<0.05),and there was no significant difference between the results of their combination and arthroscopy(both P>0.05).Dynamic ultrasound,3.0T MRI alone and their combination had high consistency of location(Kappa=0.755,0.826,0.897)and classification of knee synovial plica with those of arthroscopy(Kappa=0.721,0.744,0.860).Conclusion Dynamic ultrasound combined with 3.0T MRI was valuable for diagnosing and typing of synovial plica of knee joint.
4.The characteristics and influencing factors of medicine cost for orthopedic surgery patients in hospitals of Shanxi province
Weipeng LI ; Nan SHANG ; Zhiqi ZHANG ; Yun LI ; Xiaojun ZHENG
China Pharmacy 2024;35(5):612-617
OBJECTIVE To analyze the characteristics and influencing factors of medicine cost for orthopedic surgery patients in Shanxi province, and to provide reference for the rational management of medicine cost in orthopedic surgery patients. METHODS A retrospective analysis was conducted on the case information of 584 204 orthopedic surgery patients in Shanxi province from 2016 to 2021. Medicine cost was analyzed by year, region, hospital level, type of surgery and type of surgical incision. Single factor analysis and generalized linear regression model were used to analyze the influencing factors of total medicine cost, and structural equation model was used for verification. RESULTS The research findings indicated that joint replacement surgery (42.61%) and post-fracture external fixation surgery (12.60%) were the most common types of procedures. There was statistical significance in medicine cost for different surgical types among different regions and hospital levels (P<0.05). In the Jinzhong region, the total medicine cost for post-fracture external fixation surgery was the highest ([ 11 719.97±4 374.73) yuan], while in tertiary grade A hospitals, the total medicine cost for post-fracture external fixation surgery was also the highest ([ 13 584.71±4 531.82) yuan]. Among class Ⅰ incision surgeries, the cost of antibiotics for post-fracture external fixation surgery was the highest ([ 1 176.25±341.42) yuan]. Generalized linear regression model revealed that hospital location, hospital level, gender, payment method, length of hospital stays, and surgical type were the independent influencing factors for total medicine cost (P<0.05). Structural equation model further disclosed that hospital level, payment type, and surgical type had significant effects on total medicine cost (P<0.05). CONCLUSIONS Attention should be paid to the high cost of antibiotics for class Ⅰ incision surgery, and further research on their rational use should be conducted.
5.Fingerprint and Identification of Chemical Constituents of the Extract of Fructus Ligustri Lucidi-Ecliptae Herba
Yutong GAO ; Xiuping SONG ; Nan LI ; Yonglin SHANG ; Fei HAN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(4):399-412
OBJECTIVE To establish high performance liquid chromatography(HPLC)fingerprints of the extract of Fructus Li-gustri Lucidi-Ecliptae Herba and to identify the structure of its chemical constituents.METHODS The chromatographic separation was performed on ZORBAX Extend C18(250 mm×4.6 mm,5 μm)column with the mobile phase consisting of acetonitrile and 0.1%formic acid solution in gradient elution mode at a flow rate of 1.0 mL·min-1.The optimum column temperature was set at 35℃,the detection wavelength was 265 nm,and the injection volume was 10 μL.The HPLC fingerprints of 15 batches of herb pair from different origins were established.Then,similarity evaluation,cluster analysis,and orthogonal partial least squares discriminant analysis were carried out.The chemical structures of the constituents of the herb pair were identified based on the high-resolution mass spectrometry utilizing the UPLC-Q-Exactive Orbitrap MS in positive and negative-ion modes.RESULTS As a result,the similarity of the 15 bat-ches of samples varied from 0.865 to 0.992.A total of 16 common peaks were identified in the fingerprints,and 7 of them were identi-fied by comparision with the reference substances.Furthermore,55 chemical compounds were detected,and 7 of them were accurately identified based on the reference substances,and the chemical structures of the rest 48 components were temporarily speculated.CON-CLUSION The fingerprint method established in this study is simple,reliable,and reproducible,and can be further used for the quality control of Fructus Ligustri Lucidi-Ecliptae Herba herb pair.The developed UPLC-Q-Exactive Orbitrap MS method can be applied to identify the structures of chemical constituents in this herb pair and lay a foundation for further research.
6.Establishment and application for evaluation system of pathogen detection rate indicators before antimicrobial treatment
Lei-Lei GUO ; Hong-Ying QIN ; Sai-Nan XU ; Zhen-Zhen WU ; Yi ZHANG ; Shang-Shu ZHANG ; Hong-Kai LIAN
Chinese Journal of Infection Control 2024;23(6):712-718
Objective To establish an evaluation system of pathogen detection rate of hospitalized patients before antimicrobial treatment based on process and outcome indicators,and study its application effect.Methods Hospi-talized patients with therapeutic antimicrobial treatment in a tertiary first-class hospital from July 2022 to June 2023 were selected as the study objects.Difference in process and outcome indicators were compared between before(Ju-ly-December 2022,control group)and after(January-June 2023,intervention group)the implementation of inter-vention in the evaluation system for pathogen detection rate of hospitalized patients before antimicrobial treatment.Results 41 577 and 27 052 hospitalized patients received therapeutic antimicrobial agents were included in the inter-vention group and control group,respectively.Pathogen detection rate and the accurate pathogen detection rate in the intervention group were both higher than those in the control group(74.2%vs 62.8%and 90.3%vs 82.5%,respectively),both with statistically significant differences(both P<0.001).The goal achievement rate and im-provement rate for pathogen detection rate were 237.5%and 18.2%respectively,the goal achievement rate and im-provement rate for accurate pathogen detection rate were 104.0%and 9.5%respectively.For the process indica-tors,the conformity rate of detection and diagnosis,accurate collection rate,timely transfer rate,acceptance rate of pathogen specimens in the intervention group were all higher than those in the control group,differences were all statistically significant(all P<0.001).For the outcome indicators,detection rates of targeted indicators and blood culture specimens,pathogen detection rate before treatment of restricted and special grade antimicrobial agent,as well as detection rate of sterile body fluid specimens in the intervention group were all higher than those in the con-trol group,with statistical significance(all P<0.05).In addition,the positive rate of blood culture specimens in-creased from 18.5%before intervention to 21.7%after intervention,with statistically significant difference(P<0.05).Conclusion The establishment of indicator evaluation system can improve the detection rate and accurate detection rate of pathogens before antimicrobial treatment,as well as the management quality and connotation of indicators.
7.Application of a machine learning-assisted prescription rationality prediction model in perioperative rational drug use management
Lijuan FAN ; Zhiqi ZHANG ; Xiaojun CHENG ; Xiunan YUE ; Haiyan CHENG ; Nan SHANG
Chinese Journal of Pharmacoepidemiology 2024;33(11):1219-1228
Objective To explore the influencing factors of rational perioperative drug use,and to establish a rationality prediction model based on machine learning to assist pharmacists in prescription review.Methods A retrospective analysis was conducted on the perioperative prescription data of neurosurgery patients from a tertiary hospital and a central hospital in Shanxi Province between March 2021 and March 2023.Univariate analysis and multivariate Logistic regression were initially used to identify factors influencing rational drug use,followed by Lasso regression and multicollinearity analysis to select important variables.The data was split into a training set and test set at a ratio of 7∶3,and decision tree(DT),multi-layer perceptron(MLP),extreme gradient boosting(XGBoost),support vector machine(SVM),and random forest(RF)learning models were constructed.Results A total of 1 500 prescriptions were included,of which 668 were classified as rational and 832 as irrational.In both the training and test sets,the AUC values of the DT,XGBoost,and RF models exceeded 0.9.The DT model showed the highest sensitivity(0.81),while the RF model demonstrated the highest specificity(0.90).In the RF model,the number of comorbidities,preoperative waiting time,total hospitalization cost,prescribing physician's title,and adverse reaction occurrence negatively impacted prescription rationality,whereas the number of drugs,age,and administration route positively influenced rationality.Conclusion The machine learning-based rational drug use prediction model demonstrates strong predictive performance,effectively assisting pharmacists in prescription review and helping to reduce the incidence of irrational drug use.
8.Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis
Guang-Xun LIN ; Li-Ru HE ; Jin-Niang NAN ; Wen-Bin XU ; Keyi XIAO ; Zhiqiang QUE ; Shang-Wun JHANG ; Chien-Min CHEN ; Ming-Tao ZHU ; Gang RUI
Neurospine 2024;21(1):261-272
Objective:
This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages.
Methods:
A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications.
Results:
The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates.
Conclusion
Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.
9.Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction
Qi Yan NAN ; Shang Guo PIAO ; Ji Zhe JIN ; Byung Ha CHUNG ; Chul Woo YANG ; Can LI
Kidney Research and Clinical Practice 2024;43(5):586-599
Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.
10.Analysis of influencing factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries
Ya-Zhen BAI ; Tong-Tong ZHENG ; Meng-Nan FAN ; Yi-Ru SHANG ; Gan-Qin DU ; Qi-Zhi FU
Medical Journal of Chinese People's Liberation Army 2024;49(10):1117-1122
Objective To explore the incidence and risk factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries and its correlation with preoperative risk assessment of cerebrovascular events,so as to guide perioperative risk management.Methods A retrospective study was conducted on 40 patients aged≥18 years who underwent non-cardiac and non-neurosurgical surgeries and experienced perioperative ischemic stroke in the First Affiliated Hospital of Henan University of Science and Technology from January 2015 to January 2022,forming the stroke group.A control group of 160 patients without perioperative ischemic stroke was selected in a 1:4 case-control ratio,matched for gender,age,date of operation,and the surgeon.Clinical data and preoperative risk assessment of cerebrovascular events(including the single or combined application of head CT/MRI,transcranial Doppler ultrasound,carotid ultrasound,and neurological consultation)of the two groups of patients were collected and statistically analyzed.Multiple logistic regression analysis was used to identify risk factors associated with perioperative ischemic stroke.Results The incidence of perioperative ischemic stroke was 0.042%.Multiple logistic analysis results showed that hypertension(OR=7.858,95%CI 2.175-28.388,P=0.002),hyperlipidemia(OR=4.457,95%CI 1.320-15.049,P=0.016),renal insufficiency(OR=8.277,95%CI 1.480-46.282,P=0.016),and intraoperative hypotension(OR=3.862,95%CI 1.211-12.317,P=0.022)were independent risk factors for perioperative ischemic stroke in non-cardiac and non-neurological surgeries;preoperative cerebrovascular risk assessment(OR=0.130,95%CI 0.031-0.542,P=0.005)was a protective factor against it.Conclusions The incidence of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgery is low but has a poor prognosis.Hypertension,hyperlipidemia,renal insufficiency,and postoperative hypotension are risk factors for perioperative ischemic stroke,while preoperative cerebrovascular event risk assessment is beneficial to reducing its incidence.

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