Objective:To investigate the expression and clinical significance of SKA3 protein in cholangiocarcinoma, and the effect of interfering SKA3 expression in vitro on the proliferation, invasion, and migration of cholangiocarcinoma SSP-25 cells, as well as its possible mechanism.Methods:The clinicopathological data, cancer tissues, and paracancerous tissues from 172 patients with distal cholangiocarcinoma in Beijing Friendship Hospital, Capital Medical University between January 2015 and December 2020 were retrospectively collected. Immunohistochemical method was used to detect the expression level of SKA3 protein in cancer tissues and paracancerous tissues. Transfection of SKA3 small interfering RNA (siRNA) into cholangiocarcinoma SSP-25 cells was used as si-SKA3 group, and the untreated SSP-25 cells were used as the control group. Cell immunofluorescence staining and Western blot were used to detect the transfection effect; CCK-8 method and cell colony formation experiment were used to observe changes in cell proliferation; cell scratch assay was used to monitor cell invasion; Western blot was used to detect the expression of PI3K-AKT signaling pathway related proteins.Results:Among 172 patients with cholangiocarcinoma, there were 116 males and 56 females; the age of 54 cases was under 60 years, and age of 118 cases was equal to or more than 60 years. The positive rate of SKA3 protein in cholangiocarcinoma tissues was higher than that in paracancerous tissues [78.49% (135/172) vs. 13.95% (24/172)], and the difference was statistically significant ( χ2 = 42.78, P < 0.01). The positive rate of SKA3 protein in cancer tissues of cholangiocarcinoma patients with nerve invasion [84.35% (124/147) vs. 44.00% (11/25)] and lymph node metastasis [88.78% (87/98) vs. 64.86% (48/74)] was higher than that of patients without nerve invasion and without lymph node metastasis, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the positive rate of SKA3 protein in cancer tissues of patients stratified by age, gender, tumor diameter, TNM stage, and tumor differentiation (all P > 0.05). The CCK-8 method showed that after 72 h of cultivation, the proliferation ability of SSP-25 cells in the si-SKA3 group (expressed as absorbance value at 450 nm) was lower than that in the control group (0.56±0.05 vs. 0.83±0.06), and the difference was statistically significant ( t = 3.06, P = 0.06). After 2 weeks of cultivation, the colony formation experiment showed that the number of colony formation of SSP-25 cells in the si-SKA3 group was lower than that in the control group. After 24 h of cultivation, the scratch healing rates of SSP-25 cells in the si-SKA3 group and the control group were (31±6) % and (72±5)%, respectively, and the difference was statistically significant ( t = 5.63, P = 0.013).Western blot analysis showed that the relative expression levels of p-PI3K and p-AKT proteins in the PI3K-AKT signaling pathway were lower than those in the control group, and the difference was statistically significant (all P < 0.05). Conclusions:SKA3 protein is highly expressed in cholangiocarcinoma tissues, and may related to nerve invasion and lymph node metastasis. Interfering SKA3 expression can inhibit the proliferation and invasion of cholangiocarcinoma SSP-25 cells, and its mechanism may be related to the inhibition of the PI3K-AKT signaling pathway.

Objective To investigate the effect of pelvic floor muscle training based on timing theory in patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 112 patients undergoing robot-assisted laparoscopic radical resection of prostate cancer in the First Affiliated Hospital of Fujian Medical University were selected as the study subjects from August 2021 to August 2022.57 patients in control group were given routine intervention measures,and 55 patients in experimental group were given pelvic floor muscle intervention based on timing theory on the basis of routine intervention measures.The intervention lasted for 1 year.The intervention effects of urinary control ability,urinary incontinence recovery rate and pelvic floor function rehabilitation were compared between two groups in each period after surgery.Results 24h after catheter removal,3 months and 6 months after the intervention,the experimental group had more advantages in urinary control score,urinary incontinence recovery rate and pelvic floor function recovery score(P＜0.05),but there was no statistical significance in the above aspects between the two groups at 12 months after the operation(P＞0.05).Conclusion The pelvic floor muscle training method based on the timing theory is scientific and feasible to a certain extent,and the intervention starts before surgery and lasts until 1 year after surgery,which significantly improves the postoperative urinary incontinence symptoms of patients with robot-assisted laparoscopic radical prostatectomy within the baseline level,improves the recovery rate of urinary incontinence,and helps the early rehabilitation of patients with postoperative urinary control ability.

Objective:To analyze the types and functions of CD34 + cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods:This study was an experimental study. The CD34 + cell lineage tracing mouse was produced, and the visualization of CD34 + cells under the fluorescent condition was realized. Six male CD34 + cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34 + cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34 + cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34 + cell types, and to screen and annotate the marker genes for each CD34 + cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34 + fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results:On PID 4, CD34 + cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34 + endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34 + Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34 + CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34 + Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34 + SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34 + KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34 + CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions:CD34 + cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34 + cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Recently, malaria incidence has sharply resurgence in the border area of northern Myanmar, with the parasite incidence rate in 2023 being 21.47 times (95% CI: 18.84-24.48) that of 2019 in Kachin State's Razan and nearby areas. This resurgence caused the number of imported malaria cases to increase from 188 in 2019 to 398 in 2023 in Yunnan Province. In addition to the impact of military conflict, the border malaria joint prevention and control cooperation mechanism and malaria control measures established between China and Myanmar have failed to be implemented effectively due to the impact of the international COVID-19 epidemic. Hence, it is recommended that relevant departments evaluate the quality and effectiveness of the current cross-border transmission measures for malaria in the China-Myanmar border area from a technical perspective, and provide a large demand for primaquine, which can block the spread of malaria and cure vivax malaria, in response to the current prevalent characteristics of vivax malaria predominating in northern Myanmar. Moreover, to effectively reduce the mortality of imported malaria patients and prevent re-importation and transmission, it is necessary to enhance clinical physicians' knowledge, awareness, and vigilance regarding malaria diagnosis and treatment in the Yunnan border region, as well as China's ability and quality of appropriate response to imported malaria.

Objective Analyzing risk factors for prolonged ICU stay after cardiac surgery of Infective Endocarditis(IE)provides a basis for preventing extended ICU durations in postoperative IE cases.Methods From January 1,2019,to March 31,2021,a total of 223 patients with infective endocarditis who underwent cardiac surgery in the cardiac surgery department of Guangdong Provincial People's Hospital were included.Patients were divided into non-prolonged group(<3 days)and prolonged group(≥3 days)based on postoperative ICU stay duration.There were 156 cases in the non-prolonged group and 67 cases in the prolonged group.Single-factor analysis of risk factors for prolonged ICU stay was conducted using t-tests or rank-sum tests.Variables with P<0.05 in the single-factor analysis were further subjected to binary logistic regression for multivariate analysis.The accuracy of the model was evaluated using the ROC curve.Results Among the 223 patients,67 experienced prolonged ICU stay,with an incidence rate of 30%.Single-factor analysis results included gender,age,history of coronary heart disease,history of stroke,preoperative heart failure,aortic valve regurgitation area,left ventricular end-diastolic diameter,left ventricular ejection fraction(LVEF)<60%,extracorporeal circulation time,aortic cross-clamp time,use of Intra-Aortic Balloon Pump(IABP),endotracheal tube reintubation,pulmonary infection,use of Continuous Renal Replacement Therapy(CRRT),and prolonged mechanical ventilation time(>24 hours),among others.Multivariate analysis results revealed that preoperative LVEF<60%(OR=3.004,P=0.041),postopera-tive use of IABP(OR=31.686,P=0.008),and mechanical ventilation time>24 hours(OR=8.135,P<0.001)were independent risk factors for prolonged ICU stay after cardiac surgery.The model's AUC value for predicting risk factors for prolonged ICU stay was 0.858(95%CI:0.806～0.901,P<0.001).Conclusion Preoperative left ventricular ejection fraction(LVEF)<60%,the use of IABP,and mechanical ventilation time>24 hours were identified as independent risk factors for prolonged ICU stay after infective endocarditis(IE)surgery.In clinical practice,it is important to comprehensively address and manage various risk factors with the aim of reducing ICU stay duration and improving the overall success rate of the surgery.

Objective:To investigate the predictive efficacy of apparent diffusion coefficient(ADC),exponential ADC(eADC)of preoperative magnetic resonance diffusion-weighted imaging(MR-DWI)combined with serum alpha fetoprotein(AFP)for microvascular invasion(MVI)in patients with hepatocellular carcinoma(HCC).Methods:A prospective study was conducted on 133 HCC patients who underwent liver cancer resection at Zhangjiagang Hospital of Traditional Chinese Medicine from January 2017 to February 2023.Based on whether occurred MVI in postoperative pathological diagnosis,they were divided into positive MVI group(62 cases)and negative MVI group(71 cases).The preoperative ADC values,ADC ratio(T/L),ratio of eADC value to eADC value(eT/L),serum AFP and other clinical pathological data were compared between the two groups.Multivariate logistic regression was used to analyze the risk factors of MVI in HCC patients.The receiver operating characteristic(ROC)curve and area under curve(AUC)were applied to assess the predictive efficacies of each indicator and the combined detection of all indicator for MVI.Results:The ADC value and T/L value of ADC in the positive MVI group were lower than those in the negative MVI group,while the eT/L value of eADC was higher than that in the negative MVI group,and the differences were statistically significant(t=3.972,5.297,3.521,P<0.05),respectively.There was no statistically significant difference in eADC values between the positive MVI group and the negative MVI group(P>0.05).The serum AFP level in the positive MVI group was higher than that in the negative MVI group,and the difference was statistically significant(U=3.615,P<0.05).The tumor diameter,alanine aminotransferase(ALT)and total bilirubin(TBil)level in the positive MVI group were higher than those in the negative MVI group,and the differences were statistically significant(t=7.686,2.083,2.923,P<0.05),respectively.The proportions of patients with multiple lesions,clinical stage Ⅲ,low differentiation and incomplete capsule in the positive MVI group were higher than those in the negative MVI group,and the differences were statistically significant(x2=6.656,4.600,9.030,5.328,P<0.05),respectively.Multivariate logistic regression analysis showed that tumor diameter>5 cm,incomplete capsule,elevated AFP,decreased T/L value of ADC,the increased eT/L value in eADC were the risk factors for MVI in HCC patients(OR=1.382,1.423,1.043,0.815,1.146,P<0.05),respectively.ROC curve analysis showed that the AUC(95％CI)values of T/L value of ADC,eT/L value of eADC and AFP were respectively 0.721(0.442-0.988),0.748(0.525-0.948)and 0.720(0.460-0.985)in predicting MVI in HCC patients.The AUC(95％CI)value of the combined prediction of them was 0.860(0.731-0.974),which was higher than the predictive efficacy of single indicator.Conclusion:The decrease in T/L value of ADC in preoperative DWI,the increases of eT/L value of eADC and serum AFP are risk factors for MVI in HCC patients.The combination of preoperative T/L value of ADC,eT/L value of eADC and serum AFP has higher predictive efficacy for MVI in HCC patients.

Vision is closely tied to quality of life. Traditional drug delivery routes for clinical therapy of key ocular diseases, such as glaucoma, are topical and systemic administrations, which are less invasive but often face some physiological barriers such as tear film turnover, corneal penetration, and blood-ocular barrier. These barriers may limit penetration and distribution of ophthalmic drugs, resulting in limitation of information about pharmacokinetic characteristics of drugs in human eye. To address this, some ocular based compartment models, including classical ocular compartmental model and physiologically based pharmacokinetic(PBPK)model, have been established to illustrate dispositions of drugs in eyes. For classical ocular compartmental model, cornea or vitreous humor serves as central compartment and other ocular tissues are identified as peripheral compartments. The PBPK model, incorporating dynamic factors such as changes in ocular blood flow, effects of transporters, blood-ocular barrier, may characterize complex ocular physiology structure and dispositions of drugs in eyes. These models can contribute to development of new ophthalmic drugs and therapy strategies for ocular diseases. Here, the characteristics of drugs in eye following administrations via various routes, general ocular compartmental model and PBPK model as well as their applications in the development of new ophthalmic drugs and drug regimen for ocular diseases are reviened.

Objective To explore the dosimetric differences between abdominal deep inspiration breath hold(ADIBH)mode and free breath(FB)mode in intensity modulated radiation therapy(IMRT)for left breast cancer.Methods From July 2022 to May 2023,a total of 22 patients who needed adjuvant radiation therapy after left breast cancer surgery in the hospital were selected as the research objects.The simulated computed tomography(CT)positioning images of ADIBH and FB modes were collected,the planned target volume(PTV)and endangered organs were outlined,the IMRT plan was designed,and the dosimetric param-eters of the two modes were compared.Results There was no significant difference in the mean dose(Dmean),homogeneity index(HI)and conformity index(CI)of PTV between the ADIBH and the FB modes(P＞0.05).Compared with the FB mode,the heart Dmean,V5,V10,V20,V30 and V40 in the ADIBH mode decreased by 2.95 Gy,12.21％,8.26％,6.56％,5.41％and 3.48％,respectively,and the left anterior descending(LAD)coronary artery Dmean,maximum dose(Dmax),minimum dose(Dmin)and V40 decreased by 15.99 Gy,16.10 Gy,0.82 Gy and 13.73％,respectively,with statistical significance(P＜0.05).Compared with the FB mode,the dose and volume of heart irradiation in the ADIBH mode at the same level were significantly reduced.Pearson correlation analysis showed that there was a positive correlation between heart Dmean and LAD Dmean in the ADIBH mode(r=0.72),and between heart Dmean and LAD Dmean in the FB mode(r=0.69).Compared with the FB mode,the left lung Dmean of the ADIBH mode decreased by 0.99 Gy,and the difference was statistically significant(P＜0.05).However,there was no significant difference in left lung V5,right lung Dmean and right breast Dmean between the two breathing modes(P＞0.05).Conclusion ADIBH mode can effectively reduce the dose to the heart and LAD,and play a good protective role.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.