[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Objective To explore the effectiveness of Guasha therapy with Fufu Tongbian in treating cancer-related insomnia(CRI)and seek a new approach to managing CRI.Methods Sixty patients with CRI who were admitted to the oncology department of our hospital from July 2021 to July 2022 were engaged in the study.The patients were randomly divided equally into two groups by using the PROCPLAN process in SAS software.The patients in the control group were given conventional symptomatic treatment and the patients in the trial group were managed with Guasha therapy with Fufu Tongbian in addition to the conventional symptomatic treatment.The two groups were compared in terms of clinical efficacy as well as scores by the Pittsburgh sleep quality index(PSQI),Hamilton depression scale(HAMD),and Hamilton anxiety scale(HAMA)were compared after 2 courses of treatment.Results All patients had completed the study.The trial group exhibited significantly higher total effective rate and presented significantly lower scores on PSQI,HAMD and HAMA compared to the control group(all P＜0.001).Conclusion Guasha therapy with Fufu Tongbian can improve sleep condition of CRI patients and alleviate their depression and anxiety,thus improving sleep quality of CRI patients.

Objective Comprehensively analyzing the epilepsy-related genes by bioinformatics methods,and to explore their functions based on network and pathway analysis.Methods I Collected epilepsy-related genes through OMIM,DisGeNET,GeneCards databases and literatures deposited in PUBMED.Performed gene ontology(GO)and pathway enrichment analysis using"ClusterProfiler"R package,and the correlation between pathways was identified through pathway crosstalk analysis.Epilepsy-related genes were then mapped to human protein-protein interaction network(PPIN)to obtain epilepsy-specific PPIN,and extracted the hub and potential genes based on network topology.Results A total of 572 epilepsy-related genes were collected,642 significant GO biological process items and 80 Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways,including learning,memory and cognition,were obtained by enrichment analysis.Based on PPIN analysis,10 hub genes of the epilepsy were extracted and most of them are gamma-aminobutyric acid(GABA)receptor genes.By integrating PPIN and WGCNA analysis,17 potential genes were extracted,involving heat shock protein,growth factor receptor binding protein,etc.Conclusion Epilepsy is a complex process,involving the abnormality of multiple functional genes,multiple biological processes and pathways are closely contact through multiple functional genes,and collectively lead to the occurrence of epilepsy.

Objective Through factor analysis of the quantified syndrome information of 558 cases of kidney yang deficiency syndrome,the constructing feature of kidney yang deficiency syndrome was revealed,which provides clinical data support for the objectification,standardization and normalization of kidney Yang deficiency syndrome.Methods Firstly,the frequency analysis of symptoms,tongue and pulse signs of 558 patients with kidney Yang deficiency syndrome was carried out,and then the main syndrome information of the patients with kidney Yang deficiency syndrome was quantified.Finally,the common factors and their representative variables of kidney Yang deficiency syndrome were screened out through factor analysis,and the constructing feature of kidney Yang deficiency syndrome was analyzed combined with TCM syndrome knowledge.Results Eight common factors with eigenvalues greater than 1 were extracted by principal component analysis,and the cumulative contribution rate was 60.483%.After the factor rotation,the representative variables with the absolute value of load coefficient greater than 0.45 in each common factor were selected.The representative variables of F1 are afraid of cold and fond of warmth(0.947)and intolerance to cold(0.932).The representative variables of F2 are waist pain(0.754),waist and knee weakness(0.720)and cold in waist and knees(0.466).The representative variables of F3 are depression(0.749),insomnia(0.711)and diarrhoea(0.470).The representative variables of F4 are thin fur(0.819)and white fur(0.768).The representative variable of F5 are tinnitus and deafness(0.687),frequent nocturnal urination(0.591)and decreased libido(0.587).The representative variables of F6 are pulse sinking(0.766)and pulse weakness(0.736).The representative variables of F7 is thready pulse(0.942).The representative variable of F8 is pale tongue(0.961).External syndrome of disease location involved in these common factors are waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.The disease nature involved in these common factors is deficiency and cold.Conclusion The basic constituent units of kidney Yang deficiency syndrome include disease location syndrome elements and disease nature syndrome elements.The disease location is kidney,and the abnormal changes of kidney location are mainly external symptoms of waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.Its disease nature is deficiency and cold.Yang deficiency leads to external cold.Yang Qi deficiency can not warm the body surface resulting in the appearance of external cold syndrome.

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

ObjectiveTo analyze the characteristics of kidney Yang deficiency syndrome in different stages and time evolution of chronic kidney disease （CKD） to explore the evolution patterns of kidney Yang deficiency syndrome in CKD. MethodThe evidence information of 256 patients with CKD was collected from October 2020 to September 2022 according to relevant standards， and the "Kidney Yang Deficiency Syndrome Evaluation Scale for Chronic Kidney Disease" was developed. With SPSS Statistics 20.0， SPSS Modeler 18.0， Gephi 0.9.2， and R 4.2.1， the syndrome information of CKD patients at various stages and the syndrome changes after one year were statistically analyzed using complex network analysis， association rule analysis， probability transition matrix analysis， and chi-square test， and the kidney Yang deficiency syndrome of patients at various stages was comprehensively evaluated. ResultIn the CKD population， the proportion of females with kidney Yang deficiency syndrome was higher than that of males （P<0.01）， and the proportion of people over 65 years old was higher than in people under 65 years old. The proportion of people with kidney Yang deficiency syndrome increased with the progression of kidney disease， and the proportion of Ⅳ-Ⅴ CKD patients with kidney Yang deficiency syndrome was higher than that of Ⅰ-Ⅱ CKD patients （P<0.01）. From Ⅰ CKD to Ⅴ CKD， the frequency of dull tongue continued to increase， and the frequency of enlarged tongue and tooth-marked tongue continued to increase after Ⅲ CKD. The frequency of thick coating and greasy coating ranked in the top 3 of frequency distribution in Ⅴ CKD. After Ⅲ CKD， the top 3 tongue characteristics were weak pulse， deep pulse， and thready pulse， all of which were characteristics of kidney Yang deficiency syndrome. Complex network analysis of the tongue and pulse showed that the core tongue and pulse characteristics of patients with end-stage CKD were tooth-marked tongue with white coating and deep and thready pulse. The results of symptom frequency analysis and complex network analysis showed that aversion to cold and preference for warmth， weakness of the knees， and cold extremities were the top 3 symptoms in Ⅰ-Ⅲ CKD patients with kidney Yang deficiency syndrome， and in Ⅳ-Ⅴ CKD， the manifestations of the syndrome of Yang deficiency and water diffusion， such as drowsiness and fatigue， edema， and frequent urination at night became characteristic symptoms. The scores of edema， pale complexion， soreness and weakness of the waist and knees， loose stools， and mental depression symptoms， as well as the total score of kidney Yang deficiency syndrome gradually increased with disease progression， with statistical differences between different stages of CKD （P<0.05， P<0.01）. The frequency analysis of disease-related syndrome elements showed that the frequencies of Yang deficiency syndrome， phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome gradually increased with disease progression， and there were statistically significant differences in the distribution between different stages of CKD （P<0.05， P<0.01）. The results of complex network analysis showed that Yang deficiency syndrome was the core syndrome element throughout all stages of CKD and was the main syndrome element type of CKD， while phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome were gradually revealed in the middle and late stages of CKD. In the CKD population with kidney-Yang deficiency syndrome， the distribution of phlegm-dampness syndrome， blood stasis syndrome， and turbidity-toxin syndrome as concurrent syndromes in different CKD stages had statistically significant differences （P<0.05， P<0.01）. The association rule analysis showed that as the disease progressed， associations between the concurrent syndromes， such as phlegm-dampness syndrome， blood stasis syndrome， turbidity-toxin syndrome， and fluid retention syndrome， and kidney-Yang deficiency syndrome were gradually enhanced. The comparison of the changes in CKD with kidney Yang deficiency syndrome within one year showed that the disease location was centered on the kidney and transmitted between the spleen， stomach， heart， and liver. There is a 23.81% probability of kidney-Yang deficiency syndrome transforming into Qi deficiency syndromes （Qi deficiency in the spleen and kidney， Qi deficiency in the liver， and Qi deficiency in the heart）， 23.79% into Yin deficiency syndromes （Yin deficiency in the liver and kidney， Qi and Yin deficiency， and Yin deficiency in the liver and stomach）， and 9.52% into dampness syndromes （phlegm-dampness internal obstruction and wind-dampness obstruction）. In contrast， 20% of spleen and kidney Qi deficiency syndrome transformed into kidney Yang deficiency syndrome， and 33.33% of Qi deficiency and blood stasis syndrome transformed into kidney Yang deficiency syndrome. ConclusionAs Ⅰ CKD progresses to Ⅴ CKD， the severity of kidney Yang deficiency syndrome gradually increases， and the syndrome characteristics of kidney Yang deficiency become pronounced. Furthermore， the pathogenic factors， such as phlegm-dampness， blood stasis， and turbidity-toxin， gradually increase. With the change of time， kidney Yang deficiency syndrome in CKD tends to evolve into syndromes related to Qi deficiency， Yin deficiency， and dampness. The discovery of these rules provides a theoretical basis and reference guidance for the treatment of CKD based on syndrome differentiation.

Objective:To compare the efficacy of domestic and imported hemostatic clips in preventing delayed post-polypectomy bleeding (DPPB) after endoscopic resection of colorectal polyps ≥ 10 mm.Methods:Clinical data of 789 patients who underwent endoscopic resection of colorectal polyps (polyp diameter ≥10 mm) in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2019 were collected. The patients were divided into DPPB group ( n=15) and non-DPPB group ( n=774). Univariate and multivariate logistic regression models were used to analyze the influential factors for DPPB. The patients using one type of hemostatic clip were divided into the domestic hemostatic clip group ( n=499) and the imported hemostatic clip group ( n=208). The efficacy of hemostatic clips in preventing DPPB in the two groups was compared. Results:Among the 789 patients undergoing endoscopic resection of colorectal polyps, 1.9% (15/789) suffered from DPPB. Multivariate logistic regression analysis showed that pedunculated polyp was an independent risk factor for DPPB ( OR=6.621, 95% CI: 2.278-19.241, P=0.001), and closure of mucosal defect was an independent protective factor for DPPB ( OR=0.169,95% CI: 0.050-0.570, P=0.004). Regardless of physician experience, there was no significant difference between the domestic and imported hemostatic clip group in preventing DPPB after endoscopic resection of colorectal polyps ≥10 mm [experienced physicians: 1.8% (7/385) VS 0.6% (1/175), χ2=1.314, P=0.445; common physicians: 2.6% (3/114) VS 3.0% (1/33), χ2=0.010, P>0.999]. The domestic hemostatic clip group paid for less medical expenses than the imported hemostatic clip group (experienced physicians: 1 433.51±889.02 yuan VS 3 033.97±1 686.87 yuan, t<0.001 , P<0.001; common physicians: 1 181.58±815.29 yuan VS 3 303.46±1 690.43 yuan, t<0.001 ,P<0.001). Conclusion:Pedunculated polyp is an independent risk factor for DPPB after endoscopic resection of colorectal polyp larger than 10 mm, and clipping can significantly reduce the risk for DPPB. There is no significant difference in the prevention of DPPB between domestic and imported clips, but domestic clips compared with imported clips yield less medical burden, which are suitable for promotion to primary hospitals and major clinical centers.

Objective:The study aims to analyze the problems faced in the clinical research and management of stem cells, explore the construction of the entire process of stem cells clinical research, and promote the healthy and orderly development of the clinical research of stem cells.Methods:By consulting the literature and retrieval of relevant policies and regulations, this study analyzed the problems faced by the supervision and management department, medical institutions and researchers, this study and discussed the countermeasures for strengthening the management of the entire process of clinical research of stem cells in medical institutions.Results:There were imperfect internal system and poor management process, insufficient quality control of cell products, low quality of project management, and insufficient clinical research consciousness of stem cell clinical research management in medical institutions.Conclusions:Combined with the current management measures, guidance principles and medical institutions, we should improve the internal system of medical institutions, promote the centralized management and informatization construction of projects, strengthen cell quality control in the hospital, cultivate talent echelons and improve academic and ethical review capabilities, actively explore the management model that is suitable for the entire process of stem cell clinical research for medical institutions in China.

Objective:To analyze the risk factors for the most common adverse events, i.e. abdominal pain and distension in sedation-free colonoscopy.Methods:This was a multicenter clinical study, in which clinical data of patients including outpatients and inpatients who underwent selective sedation-free colonoscopy at six gastrointestinal endoscopy centers from July 2017 to December 2019 were collected, including patients' general information, complicating diseases, examination time, examination results, and occurrence of adverse events of abdominal pain and distension. Univariate and multivariate logistic regression was performed to analyze the risk factors for adverse events of abdominal pain and distension during sedation-free colonoscopy.Results:A total of 2 394 patients underwent sedation-free colonoscopy, among whom 690 (28.8%) suffered from abdominal pain, and 1 151 (48.1%) experienced abdominal distension. The results of multivariate logistic analysis showed that overweight ( OR=1.33, 95% CI:1.09-1.62, P=0.005), obesity ( OR=1.55, 95% CI:1.14-2.11, P=0.005) and combination of hypertension ( OR=1.58, 95% CI:1.23-2.02, P<0.001) were independent risk factors for abdominal pain during sedation-free colonoscopy, and overweight ( OR=1.40, 95% CI:1.17-1.68, P<0.001) and combination of hypertension ( OR=1.39,95% CI:1.10-1.76, P=0.006) were independent risk factors for abdominal distension during sedation-free colonoscopy. Conclusion:Obesity, overweight and combination of hypertension are independent risk factors for abdominal pain, and overweight and combination of hypertension are independent risk factors for abdominal distension during sedation-free colonoscopy.

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.