BACKGROUND: Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients' clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens. METHODS: This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients. RESULTS: With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS ( P = 0.012) and EFS ( P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs . 6 [4, 7] days, Z = -0.227, P = 0.820). CONCLUSIONS NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Female ; Lung Neoplasms/mortality* ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy/methods* ; Retrospective Studies ; Aged ; Adult ; Kaplan-Meier Estimate ; Treatment Outcome ; Immunotherapy/methods*

Gambogic acid(GA), a caged xanthone derivative isolated from Garcinia Hanburyi, exhibits significant antitumor activity and has advanced to phase Ⅱ clinical trials for lung cancer treatment in China. However, the clinical application of GA is severely hindered by its inherent limitations, including poor water solubility, a lack of targeting specificity, and significant side effects. Novel drug delivery systems not only overcome these pharmacological deficiencies but also integrate multiple therapeutic modalities, transcending the limitations of monotherapeutic approaches. In this study, we designed a multifunctional nanodelivery platform(PDA-PEG-Fe(Ⅲ)-GOx-GA) using polydopamine(PDA) as the core material. After the modification of PDA with polyethylene glycol(PEG), Fe(Ⅲ) ions, glucose oxidase(GOx), and GA were sequentially loaded via coordination interactions, electrostatic adsorption, and hydrophobic interactions, respectively. This system demonstrated excellent physiological stability, hemocompatibility, and photothermal conversion efficiency. Notably, under dual stimuli of pH and near-infrared(NIR) irradiation, PDA-PEG-Fe(Ⅲ)-GOx-GA achieved controlled GA release, with a cumulative release rate of 58.3% at 12 h, 3.6-fold higher than that under non-stimulated conditions. Under NIR irradiation, the synergistic effects of PDA-mediated photothermal therapy, Fe(Ⅲ)-induced chemodynamic therapy, GOx-generated starvation therapy, and GA-mediated chemotherapy resulted in effective inhibition of tumor cell proliferation(91.5% inhibition rate) and induction of apoptosis(83.3% apoptosis rate). This multi-modal approach realized a comprehensive treatment strategy for lung cancer, integrating various therapeutic pathways.
Xanthones/pharmacology* ; Humans ; Polymers/chemistry* ; Glucose Oxidase/pharmacology* ; Indoles/chemistry* ; Drug Delivery Systems ; Drug Carriers/chemistry* ; Nanoparticles/chemistry* ; Cell Line, Tumor

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

ObjectiveTo reveal the correlation of Rehmannia glutinosa-soil feedback process with the formation of its continuous cropping obstacles through the identification of the root exudates of R. glutinosa and analysis of the specific rhizomicrobes recruited by the root exudate. MethodThe root exudates of R. glutinosa seedlings germinated under sterilized condition and those enriched in the rhizosphere of R. glutinosa cultivated in the field were collected and analyzed using the ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. The highly abundant compounds identified in the root exudates were added into blank soil， and the soil microbial community was profiled using Illumina Miseq sequencing. The bacterial and fungal functions were predicted by PICRUSt and FUNGuild， respectively. ResultThe identification results showed that seven phenylethanoid glycosides were found in R. glutinosa root exudates， and acteoside possessed the highest abundance. In the soil enriched with acteoside， the bacterial genera such as Agromyces， Pseudomonas， Lysobacter， Sphingobium， Pseudoxanthomonas and Sphingomonas were enriched. For the fungi， the genera Neocosmospora， Plectosphaerella and Dactylonectria， and the species such as Neocosmospora rubicola， Plectosphaerella cucumerina， Dactylonectria alcacerensis and Fusarium solani showed higher abundance. The functional analysis indicated the above-mentioned bacterial genera may realize rapid proliferation by utilizing， biodegrading and transforming phenylethanoid glycosides， and some potential fungal pathogens were colonized. ConclusionThe R. glutinsoa-soil feedbacks were likely generated by the phenylethanoid glycosides in the root exudates together with the specific rhizomicrobes. The investigations of R. glutinsoa-soil feedbacks under continuous cropping system are critical to the further understanding of the underlying mechanisms related to its continuous cropping obstacles.

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.

Objective:To study influence of exercise rehabilitation based on psycho-cardiology medical model on pa-tients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 164 CHD patients undergoing PCI in our hospital were randomly and equally divided into routine nursing group and exer-cise rehabilitation group(received exercise rehabilitation based on psycho-cardiology medical model based on rou-tine nursing group).Both groups were intervened for six months.General clinical data,score of somatic symptoms scale(SSS),cardiac function indexes:LVEF and LVEDV,6min walking distance(6MWD)and score of 36-item short-form heath survey(SF-36)were compared between two groups.Results:During follow-up,there were three cases lost in routine nursing group,and two cases lost and four cases stopped follow-up in exercise rehabilita-tion group.Compared with routine nursing group,six months after intervention,there were significant reductions in SSS score[(33.97±5.76)scores vs.(25.76±4.79)scores]and LVEDV[(125.33±16.14)ml vs.(119.53± 16.82)ml],and significant rise in LVEF[(56.28±4.46)％vs.(59.28±4.90)％],6MWD[(410.42±20.08)m vs.(439.69±20.66)m],scores of physical functioning[(19.20±4.22)scores vs.(23.76±3.98)scores],bodily pain[(7.42±1.99)scores vs.(8.84±1.94)scores],general health[(16.42±4.73)scores vs.(19.09±4.37)scores],vitality[16.0(7.0)scores vs.19.0(6.8)scores],role-emotional[(4.86±1.10)scores vs.(5.18± 0.86)scores],mental health[20.0(5.0)scores vs.24.0(8.8)scores]of SF-36 in exercise rehabilitation group(P＜0.05 or＜0.01).Conclusion:Exercise rehabilitation based on psycho-cardiology medical model can signifi-cantly improve cardiac function and psychological status,and improve quality of life in patients with coronary heart disease after PCI.

Objective Observing the feasibility of acute endovascular treatment for patients with symptomatic anterior intracranial atherosclerotic severe stenosis.Method From Jun 2019 to Jun 2023,30 symptomatic anterior intracranial atherosclerotic severe stenosis cases were retrospectively collected in the Guangdong Hospital of Traditional Chinese Medicine to evaluate the risk stratification score and explore the safety and effectiveness of acute(≤72.0h)endovascular treatment.Endovascular treatment includes balloon dilation+self-expanding stent placement,balloon-mounted stent placement,and balloon dilation.From the clinical experience,the risk stratification score was based on the ABCD3-I score for transient ischemic attacks(TIA)and additional evaluation of cerebral watershed infarction to identify the risk of stroke progression or recurrence in acute stage of symptomatic intracranial artery stenosis.The score of 0-3 was defined as low-risk,4-7 as medium risk,and 8-13 as high-risk.The successful revascularization of blood flow is determined based on the residual stenosis≤50％and the extended thrombolysis in cerebral infarction(eTICI)＞2c.The information of patient receiving endovascular treatment was recorded,including age,sex,risk factors of cerebrovascular disease(hypertension,diabetes,hyperlipidemia,hyperhomocysteinemia,drinking history,smoking history),onset data(time from onset to endovascular treatment,symptoms,progression),diseased vessels,risk stratification score,National Institutes of Health Stroke Scale(NIHSS)score before and 90 days after surgery,modified Rankin scale(mRS)score 90 days after surgery,intraoperative cerebrovascular events(intracranial hemorrhage,occlusion of responsible vessels),and postoperative cerebrovascular events 90 days after surgery(intracranial hemorrhage,cerebral infarction,TIA and in-stent restenosis)and deaths.Results Among 30 patients with symptomatic anterior intracranial atherosclerotic severe stenosis,3 patients were excluded from the time interval between onset and endovascular treatment＞72.0 hours,1 patient needed long-term anticoagulant drugs due to other diseases,1 patient lost follow-up,3 patients coexisted with other cardiogenic cerebral embolism diseases,4 patients with non-atherosclerotic arterial stenosis,and 7 patients refused emergency endovascular treatment.11 patients were finally included.(1)All 11 patients were successfully treated with endovascular treatment,and 7 were males;age ranged from 52 to 76 years old,with a median age of 64 years old;there were 9 cases with hypertension,3 cases diabetes,7 cases hyperlipidemia,2 cases hyperhomocysteinemia(only 9cases performed the examination),2cases smoking history,1 case drinking history;time from onset to endovascular treatment is 4.0-72.0 h,with a median time of 12.0 h;there were 3 and 8 cases of infarction in the left and right hemispheres,respectively,with 4,3,and 2 cases accompanied with anterior-posterior watershed,medial watershed,and anlerior-medial-posterior watershed infarctions,and 1 case accompanied by posterior-medial,anterior-medial watershed infarctions.(2)Among the 1 1 patients,the risk stratification score was 10-13 points,with a median score of 11 points;preoperative NIHSS score ranged 0-11 points,with a median score of 7 points.(3)Among the 1 1 patients,10 lesions located in the middle cerebral artery and 1 in the C7 segment of the internal carotid artery;the preoperative stenosis rate was 70％to 99％,with a median stenosis rate of 86％;preoperative eTICI grading was 2a in 7 cases and 2b50 in 4 cases(with slow distal blood flow);9 cases received balloon dilation and self-expanding stent placement,1 case received balloon-mounted stent placement,and 1 case received balloon dilation treatment;the postoperative stenosis rate is 10％to 20％,with a median stenosis rate of 15％;there were 3 cases with postoperative eTICI grade 2c and 8 cases with grade 3.(4)Among the 11 patients,one experienced intracranial hemorrhage on the first day after surgery and one had a new cerebral infarction on the third day after surgery.Eight patients were followed up by imaging 90days after surgery,demonstrating 2 cases of in-stent restenosis;90 days post-surgery,NIHSS score was 0-20 points,with a median score of 2 points;after 90 days of surgery,the mRS score was 0-4 points,with a median score of 1 point.There were 8 patients with mRS score ≤ 2 and no death events occurred.Conclusions Preliminary analysis shows that acute endovascular treatment for symptomatic anterior intracranial atherosclerotic severe stenosis has certain effectiveness,but the safety needs to be further validated.The screening of high-risk patients using risk stratification scores still requires further exploration through large sample and multicenter studies.

Objective To explore the prognostic factor and its predictive value of patients with Wilson disease-related acute-on-chronic liver failure(WD-ACLF).Methods The clinical data of 70 patients diagnosed as WD-ACLF admitted to the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 1,2017 to January 1,2022 were retrospectively collected.According to the 12-week prognosis,patients were divided into survival group(n=36)and death group(n=34).The data of the two groups were analyzed by univariate and multivariate logistic analysis to screen the prognostic risk factors and evaluate their predictive value.The model coefficient is omnibus tested,and the model-fitting degree is evaluated by the Hosmer-Lemeshow test.ROC curve was used to analyze the prognostic value for WD-ACLF between the new model and chronic liver failure-sequential organ failure assessment(CLIF-SOFA)score,model for end-stage liver disease(MELD)score and Child-Turcotte-Pugh(CTP)score.Results A total of 70 WD-ACLF patients were enrolled in present study,including 36 cases in survival group[22 males and 14 females with median age of 30.0(17.3,40.0)]and 34 cases in death group[25 males and 9 females with median age of 34.0(28.8,41.0)].Univariate analysis showed that the course of disease,prothrombin time(PT),activated partial thromboplastin time(APTT)were shorter in survival group than that in death group,the white blood cells(WBC),international normalized ratio(INR),aspartate transaminase(AST),total bilirubin(TBIL),blood urea nitrogen(BUN),creatinine(Cre)and ceruloplasmin(CER)levels and the proportion of infection,ascites,and upper gastrointestinal bleeding were lower in survival group than those in death group,however,the proportion of infection,ascites and upper digestive bleeding in the survival group were lower than those in the death group.Meanwhile,the red blood cells(RBC),hemoglobin(Hb),Na+ and total cholesterol(TC)level in the survival group were higher than those in the death group(P<0.05 or P<0.01).The results of multivariate logistic regression analysis showed that disease course(OR=1.176,95%CI 1.043-1.325),INR(OR=7.635,95%CI 1.767-32.980),TBIL(OR=1.012,95%CI 1.003-1.021),and upper gastrointestinal bleeding(OR=11.654,95%CI 1.029-131.980)were independent risk factors affecting the prognosis of WD-ACLF(P<0.05).Based on the results of logistic regression analysis,a joint model for predicting the prognosis of WD-ACLF was established.The AUC of the model for evaluating the prognosis of WD-ACLF was 0.941,which was greater than the CLIF-SOFA score(AUC=0.802),MELD score(AUC=0.897),and CTP score(AUC=0.722).Conclusions The course of disease,TBIL,INR,and upper gastrointestinal bleeding are risk factors that affect the prognosis of WD-ACLF.The prognosis model established based on this can more accurately predict the prognosis of WD-ACLF patients,and its predictive value is superior to CLIF-SOFA score,MELD score,and CTP score.

Objective To explore the commonly used acupoints and stimulation parameters of electroacupuncture in the treatment of diabetic peripheral neuropathy(DPN)through data mining.Methods The clinical research literature of electroacupuncture in the treatment of DPN was retrieved from CNKI,Wanfang,VIP,CBM and PubMed from the establishment of the database to May 2023.The database of acupoint selection and electroacupuncture stimulation parameters for electroacupuncture in the treatment of DPN was established.Descriptive statistics,cluster analysis and association rule analysis were performed on the data.Results The 36 prescriptions in the 36 included literatures were analyzed.The top three acupoints with high frequency of use were:Sanyinjiao(SP6),Zusanli(ST36)and Hegu(LI4);acupoints are mainly bladder meridian of foot bladder meridian,stomach meridian of foot yangming,spleen meridian of foot taiyin;through cluster analysis,8 cluster clusters were obtained.The core prescription of'Hegu,Zusanli,Sanyinjiao'was obtained by association rule analysis,and the most supported acupoint combination was'Zusanli-Sanyinjiao'.The most commonly used stimulation parameters were continuous wave,density wave,5 Hz,intensity tolerance,30 minures/time,1 time/day,and the total treatment time was 4 weeks.Conclusion The core acupoints of electroacupuncture in the treatment of DPN are Hegu,Zusanli and Sanyinjiao.Electroacupuncture parameters recommended 5 Hz,continuous wave,30 minutes/time,1 time/day,treatment for 4 weeks.It can provide some reference for clinical acupoint selection and parameter selection of electroacupuncture in the treatment of DPN.