ObjectiveTo observe the clinical efficacy of Tongfu Kuanzhong decoction （TFKZ） in the treatment of constipation-predominant irritable bowel syndrome （IBS-C） with spleen deficiency and Qi stagnation and its effects on anorectal manometry and colonic electrical activity parameters. MethodsSixty-four patients with IBS-C of the spleen deficiency and Qi stagnation type were included as research subjects and were randomized into the observation group （thirty-two cases） and control group （thirty-two cases）. The control group was orally administered mosapride citrate tablets， and the observation group was orally administered TFKZ. Both groups were treated for 4 weeks. The traditional Chinese medicine （TCM） syndrome scores， patient assessment of constipation symptoms （PAC-SYM） score， general anxiety disorder-7 （GAD-7） score， patient health questionnaire-9（PHQ-9）score， anorectal manometry， and colonic electrical activity parameters were observed before and after treatment in the two groups. ResultsThe total points of TCM syndromes were significantly lower in both groups after treatment （P<0.01） and lower in the observation group （P<0.05）. The fecal symptoms， rectal symptoms， abdominal symptoms， and total symptom scores of the patients in both groups were significantly decreased after treatment （P<0.01）， and the rectal symptoms， abdominal symptoms， and total symptom scores of the observation group were lower （P<0.05，P<0.01）. In both groups， the forced anal residual pressure and the initial rectal sensation threshold decreased after treatment （P<0.05，P<0.01）， and forced anal residual pressure in the control group was lower （P<0.01）. After treatment， the GAD-7 and PHQ-9 scores of patients in both groups decreased significantly （P<0.01）， and the GAD-7 score of the observation group was significantly lower （P<0.01）. After treatment， the average wave amplitude at different time points of each lead increased significantly in both groups， compared with that before treatment （P<0.01）. The average wave amplitude of each lead of the ascending colon， descending colon， sigmoid colon， and rectum in the observation group at 5 min before the meal and 10 min after the meal， as well as that of the ascending colon and rectum at 20 min and 30 min after the meal， was higher than that of the control group （P<0.05）. ConclusionTFKZ is effective in the treatment of IBS-C. Its mechanism may be related to the regulation of colonic function by down-regulating the forced anal residual pressure and the initial rectal sensation threshold and up-regulating the amplitude and frequency of intestinal electrical activity in each intestinal segment of the colon.

OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis （DNOP） in rats. METHODS The rats were randomly divided into blank control group， control group， model group， Jingui shenqi pill low-， medium- and high-dose groups （0.62， 1.24， 2.48 g/kg）， and positive control group （denosumab 3 mg/ kg）， with 12 cases in each group. Except for the blank control group and the control group， models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage， 3% fructose solution for feeding+intraperitoneal injection of streptozotocin solution. At 2 d after successful molding， Jingui shenqi pill low-， medium- and high-dose groups， and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs， once a day， for consecutive 8 weeks. After the last administration， bone mineral density （BMD） and serum bone metabolism-related indexes [osteocalcin （OC）， calcium， phosphorus， alkaline phosphatase （ALP）， tartrate-resistant acid phosphatase （TRAP）] were detected. The pathological changes of right femoral tissues were observed， and the expressions of receptor activator of NF-κB ligand （RANKL）/receptor activator of NF-κB （RANK）/osteoprotegerin （OPG） pathway-related mRNAs and proteins in left femoral tissues were detected. RESULTS Compared with the blank control group and the control group， there was rupture of bone trabecula and severe structural damage in the model group， and tissue space was obvious. BMD and ALP activities， mRNA and protein expressions of OPG were significantly decreased or down-regulated， while the levels of OC， calcium and phosphorus， TRAP activity， mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated （P＜0.05）. Compared with the model group， the number of bone trabeculae was increased in all Jingui shenqi pill groups， and the arrangement of bone trabeculae was more regular and dense. The above indexes generally were improved in a certain dose-dependent manner （P＜0.05）. CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats， which may be related to down-regulating the expressions of RANKL and RANK， and up-regulating the expression of OPG.

Therapeutic cancer vaccines have experienced a resurgence over the past ten years. Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle, primarily by activating the immune system to promote tumor regression and overcome immune resistance. In this review, we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle, including the effector cell function, infiltration, initiation, and exhaustion. We summarize the identification of tumor antigens and their delivery through cancer vaccines. We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy. Additionally, the impact of aging and myelosuppression, two prevalent forms of immunological stress, on the effectiveness of therapeutic cancer vaccines is deliberated. Finally, we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
Humans ; Cancer Vaccines/therapeutic use* ; Neoplasms/therapy* ; Immunotherapy/methods* ; Antigens, Neoplasm/immunology* ; Animals

Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objective To systematically review and synthesize the psychological experience of kinesiophobia in patients with cardiac rehabilitation.Methods PubMed,Web of science,Journals@Ovid,Embase,CINAHL,PsycINFO,Cochrane Library,CNKI,SinoMed,WanFang Database,Vip Database,American Heart Association,European Society of Cardiology and American Association of Cardiovascular and Pulmonary Rehabilitation were searched to collect qualitative research on the psychological experience of cardiac rehabilitation patients with kinesiophobia.The retrieval time was from the establishment of the databases to Jun 2023.The literature was evaluated using the Australian JBI Quality Evaluation Criteria for Qualitative Research in Evidence-based Health Care Centres(2016),and the results were consolidated using an aggregative integration approach.Results A total of 45 results were extracted from 14 studies.Similar results were summarized into 10 groups,and 3 integrated results were synthesized as followed.Kinesiophobia was influenced by many factors;kinesiophobia affects the life experience of patients;strategies to reduce the level of kinesiophobia.Conclusion Nurses should pay more attention to psychological experience of kinesiophobia,and take the corresponding intervention measures to help patients overcome the psychological barriers of kinesiophobia,perfect personalized exercise programs,and improve the level of physical activity.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Objective To investigate the application value of ultrafast pulse wave velocity (ufPWV) technique in the assessment of carotid artery elasticity decline in the patients with simple hypertriglyceridemia (TG).Methods The patients visiting the cardiology outpatient department of Jiangsu Provincial Hospital of Traditional Chinese Medicine/Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to March 2022 were selected,the serum lipid satisfied:TG≥1.7 mmol/L,moreover total cholesterol (TC)<5.2 mmol/L,low density lipoprotein cholesterol (LDL-C)<3.4 mmol/L and high density lipoprotein cholesterol (HDL-C)>1.0 mmol/L,they were included into the simple high TG group (n=63).Sixty-eight healthy subjects undergoing physical examination in this hospital were selected as the normal blood lipid group and their blood lipid indicators TG,TC,LDL-C and HDL-C all were within the normal range.The clinical data of all subjects were collected.The ufPWV technique was used to detect the common carotid artery pulse wave velocity of beginning systole (PWV-BS),pulse wave velocity of ending systolic (PWV-ES) and carotid intima-media thickness (cIMT).Results The body mass index (BMI),systolic blood pressure,diastolic blood pres-sure,TG,fasting blood glucose (FBG),cIMT and PWV-ES value had statistical differences between the sim-ple high TG group and normal blood lipid group (P<0.05);PWV-BS,PWV-ES and cIMT were positively correlated with age,and the PWV-ES correlation was the highest (r=0.607,P<0.001),followed by cIMT (r=0.590,P<0.001),and PWV-BS (r=0.325,P<0.001) was the lowest;the Logistic regression analysis showed that PWV-ES could serve as a predictive factor of carotid artery elasticity decline in the population with simple TG,moreover which was independent of the factors such as age,gender,BMI,systolic blood pres-sure,diastolic blood pressure and FBG (OR=1.449,P<0.005).Conclusion The ufPWV technique could e-valuate the decline phenomenon of carotid artery elasticity in the population with simple high TG,and the ele-vated PWV-ES is an independent risk factor for carotid artery elasticity decline in this population.

Objective To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid(CGA)treatment of acute kidney injury(AKI)in mice.Method Twenty-four C57Bl/6J mice were randomized into sham-operated group,cecal ligation and puncture(CLP)group,CLP+dexamethasone group(CLP+DXM group),and CLP+CGA group(n=6)and subjected to either sham operation(laparotomy only)or CLP.After modeling the mice received intravenous infusion of 10 mg/kg normal saline(in sham and CLP groups),1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump.Eight hours after the infusion,renal morphology and histology,renal cell apoptosis,and the renal function parameters such as urea nitrogen(BUN),creatinine(Scr),and kidney injury molecule 1(KIM-1)were compared among the 4 groups;the 7-day survival rates of the mice were recorded,and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected.Results CGA treatment significantly improved the 7-day survival rate,reduced renal pathologies of the septic mice(P<0.05),and lowered the levels of BUN,Scr,KIM-1,NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway.Conclusion CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.

Objective:To establish the objective of zero inventory management of in vitro diagnostic reagents,to evaluate the quality of supply chain,and to improve the existing problems in the supply of reagents.Methods:The problems existing in the management of in vitro diagnostic reagents were analyzed from the aspects of inventory,supply efficiency and product quality,and the management system of hospital operation,management quality and patient benefit optimization was established,and the zero-inventory management path and quality evaluation model were constructed.85 models of 21 types of in vitro diagnostic reagents purchased by Jiangsu Subei People's Hospital from January 2020 to March 2023 were selected.According to different supply chain quality management methods,on-demand inventory management mode(referred to as mode 1)and zero inventory management mode(referred to as mode 2)were adopted respectively.The demand procurement,inventory management and clinical use effects of the two management modes were compared.Results:The reagent procurement demand compliance rate,supply capacity high-quality quality rate and clinical use matching rate of mode 2 were(93.35±3.62)%,(94.87±2.63)% and(96.08±2.31)%,respectively,which were higher than those of mode 1,the difference was statistically significant(Z=2.489,2.836,2.838,P<0.05).The number of cases of long-term overstocking of products,substandard environment and untimely information in mode 2 were(2.92±2.54)cases,(2.83±1.59)cases and(5.58±3.12)cases,respectively,which were lower than those in mode 1,the difference was statistically significant(Z=2.959,3.037,3.703,P<0.05).The satisfaction of clinical departments,medical technology departments and procurement center with the supply,distribution and information communication of in vitro diagnostic reagents in mode 2 were 97.8% and 93.3%,97.0% and 87.9%,100% and 84.6%,respectively,which were higher than those in mode 1,the difference was statistically significant(x2clinical departments=5.428,6.133,x2medical technology departments=3.958,3.937,x2procurement center=5.159,4.996,P<0.05).Conclusion:The zero inventory management model can improve the standardization of in vitro diagnostic reagent demand procurement,reduce the incidence of backlog failure in inventory management,and improve the quality of clinical supply services.