OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression (n = 113,154) and MDD (n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objectives:To examine the functional outcomes of robot-assisted radical prostatectomy (RARP) with preservation of pelvic floor stabilized structure and early elevated retrograde liberation of the neurovascular bundle (PEEL).Methods:This study was a retrospective cohort study. Between June 1, 2022, and March 20, 2023, 27 cases of RARP with PEEL and 153 cases of RARP with preservation of pelvic floor stabilized structure (PPSS) were included in this study. All patients were males, aged (62.5±5.2) years (range: 50 to 73 years). There were 18 cases of ≤T2b stage and 9 cases of T2c stage. After 1∶1 propensity score matching, the postoperative functional outcomes of 27 cases of RARP with PEEL and 27 cases of RARP with PPSS were compared. All surgeries were performed by a single surgeon and included patients were clinically staged as cT1-2N0M0 without preoperative urinary incontinence or erectile dysfunction. In RARP with PEEL, the prostate was cut near the midline at the front when dissecting the neurovascular bundle, dissection was performed between the visceral layer of the pelvic fascia and the prostatic fascia, preserving the parietal layer and the visceral layer of the pelvic fascia, and the neurovascular bundle was retrogradely released from the apex. The cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in functional outcomes between the two groups. Univariate and multivariate analysis with the Cox proportional hazards model was used to compare postoperative urinary continence and sexual function.Results:The recovery time of continence and potency was significantly longer in the PPSS group than in the PEEL group (all P<0.05). The continence rate of the PEEL group was significantly higher than that of the PPSS group (92.59% vs. 68.10%, P=0.026) at 3 months after surgery. The potency rate of the PEEL group was also significantly higher than that of the PPSS group (40.70% vs. 15.10%, P=0.037) at 3 months after surgery. In the univariate analysis, compared to the PPSS technique, the PEEL technique was associated with a shorter recovery time of continence ( HR=1.94, 95% CI: 1.08 to 3.48, P=0.027) and a shorter recovery time of potency ( HR=2.06, 95% CI: 1.03 to 4.13, P=0.042). In the multivariate analysis, the PEEL technique was an independent prognosis factor for postoperative recovery of continence ( HR=2.05, 95% CI: 1.01 to 4.17, P=0.047) and potency ( HR=3.57, 95% CI: 1.43 to 8.92, P=0.007). All the cases of the PPSS group and the PEEL group were performed successfully with negative surgical margins. Conclusion:Compared with PPSS, PEEL may be more conducive to the recovery of urinary continence and sexual function after RARP.

Objective:To assess a value of dual energy index(DEI)and effective atomic number(Zeff)of dual-energy computed tomography(DECT)combined with slope of energy spectrum curve in identifying the component of urinary tract stones.Methods:The clinical and DECT imaging data of 111 patients with urinary tract stones who admitted to Nantong Haimen People's Hospital from October 2019 to October 2022 were selected,and the diameters of the urinary tract stones of all patients were<5 mm.The components of outside body stones of all patients were analyzed by infrared spectrum.The accuracy,sensitivity and specificity of the DEI,Zeff,slope of energy spectrum curve and the combination of the them were respectively calculated in identifying the components of urinary tract stones.Results:In 111 patients,the patients with calcium oxalate stones were 75(67.57%),and ones with hydroxyapatite were 15 cases(13.51%),and ones with uric acid stones were 21 cases(18.92%),and there were no other type of stone included cysteine.The differences of CT values(F=487.691,P<0.001),DEI values(F=395.553,P<0.001),Zeff values(F=818.689,P<0.001)and the slopes of energy spectrum curves(H=19.615,P<0.001)were statistically significant among the three types of stones.The overall accuracies of DEI,Zeff and slope of energy spectrum curve were 87.39%(97/111),84.68%%(94/111)and 81.98%(91/111)in identifying the components of urinary tract stone.The range of diagnostic accuracies of DEI,Zeff and the slope of energy spectrum curve was between 80%and 100%for calcium oxalate stones,hydroxyapatite and uric acid stones.The overall accuracy of DEI,Zeff combined with slope of energy spectrum curve was 94.59%(105/111)in identifying the components of urinary tract stones.The diagnostic accuracies of DEI,Zeff combined with slope of energy spectrum curve were respectively 94.59%,94.59 and 100%for calcium oxalate stones,hydroxyapatite and uric acid stones.Conclusion:Compared with the single indicator of DECT,the DEI and Zeff combined with the slope of the energy spectrum curve showed better diagnostic accuracy in identifying the components urinary track stones.

Objective To construct the evaluation index of physical restraint nursing quality for neurosurgical patients,which can guide nurses'clinical practice and continuously improve work flow and quality.Methods Under the guidance of three-dimensional quality structure model,the evaluation index of nursing quality of physical restraint in neurosurgery patients was established by reviewing literature,interviewing experts and using Delphi expert correspondence.Results The effective recovery rate of three rounds of expert enquiry was 100％,the expert authority coefficient was＞0.9,the first and second coordination co-efficients were 0.126 and 0.094(P＜0.001),and the final evaluation index included 3 first-level indicators and 31 second-level indicators.Conclusion The established evaluation indexes are scientific,standardized and comprehensive,which can guide the nursing quality of neurosurgery patients with physical restraint.

Objective To observe the clinical efficacy of self-made Rheumatoid No.2 Formula(derived from Huangqi Guizhi Wuwu Decoction with Spatholobi Caulis,Tinosporae sinensis Caulis,Guangdong Piperis Kadsurae Caulis,Chaenomelis Fructus,etc.added)combined with Barrettinib and Methotrexate for the treatment of rheumatoid arthritis(RA)of cold-damp obstruction type.Methods Sixty patients with RA of cold-damp obstruction type were randomly divided into an observation group and a control group,with 30 cases in each group.The control group was treated with Baritinib and Methotrexate orally,and the observation group was treated with self-made Rheumatoid No.2 Formula orally on the basis of treatment for the control group.The course of treatment covered 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome score,pain visual analogue scale(VAS)score,erythrocyte sedimentation rate(ESR),serum C-reactive protein(CRP),rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(anti-CCP)and other related laboratory indicators in the two groups before and after treatment were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 8 weeks of treatment,the total effective rate of the observation group was 93.33％(28/30),and that of the control group was 70.00％(21/30).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the scores of TCM syndromes in the two groups were significantly lower than those before treatment(P＜0.05 or P＜0.01),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the VAS scores of pain in the two groups were significantly lower than those before treatment(P＜0.01),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of related laboratory indicators of ESR and serum CRP,RF and anti-CCP in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).Conclusion The self-made Rheumatoid No.2 Formula combined with Baritinib and Methotrexate exerts certain effect for the treatment of RA of cold-damp obstruction type,which can effectively alleviate the clinical symptoms and signs of patients and improve the relevant laboratory indexes of patients.Its curative effect is superior to that of western medicine of Baritinib and Methotrexate.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Pogostemon cablin is a famous southern medicine.As the important raw material for modern medicine and industry,Pogostemon cablin becomes required with a large marketing demand.However,due to the serious continuous cropping obstacles in the growth process of Pogostemon cablin,the aggravation of diseases of Pogostemon cablin and the degradation of its quality arose.This paper outlined the ecological factors such as climate factors,soil factors and topographic factors suitable for the growth of Pogostemon cablin,analyzed the continuous cropping obstacles and diseases arising in the cultivation,reviewed the current ecological planting mode of Pogostemon cablin such as crop rotation,intercropping,relay-cropping and under-forest planting,and also made a comprehensive evaluation of the economic benefits,ecological benefits and social benefits of the ecological planting mode of Pogostemon cablin,aiming to provide a theoretical basis and a reference for the promotion of the ecological planting mode of Pogostemon cablin.

Acute kidney injury(AKI)remains a global public health problem with high incidence,high mortality rates,expensive medical costs,and limited treatment options.AKI can further progress to chronic kidney disease(CKD)and eventually end-stage renal disease(ESRD).Previous studies have shown that trauma,adverse drug reactions,surgery,and other factors are closely associated with AKI.With further in-depth exploration,the role of gut microbiota in AKI is gradually revealed.After AKI occurs,there are changes in the composition of gut microbiota,leading to disruption of the intestinal barrier,intestinal immune response,and bacterial translocation.Meanwhile,metabolites of gut microbiota can exacerbate the progression of AKI.Therefore,elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.