A redox-responsive self-assembling COA-4-arm PEG prodrug nanosystem for dual drug delivery suppresses cancer metastasis and drug resistance by downregulating hsp90 expression

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.@*METHODS@#Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.@*RESULTS@#The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.@*CONCLUSION@#The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.

Influencing factors analysis of the therapeutic efficacy of targeted therapy in patients with epidermal growth factor receptor mutant advanced non-small cell lung cancer / 肿瘤研究与临床

Objective:To investigate the influencing factors of the therapeutic effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC).Methods:The clinical data of 104 EGFR mutant advanced NSCLC patients who received EGFR-TKI treatment in Wuxi No.2 Hospital Affiliated to Nanjing Medical University from January 2015 to October 2019 were collected. The correlation of different types of EGFR mutation with the clinicopathological characteristics, the hematological examination results and the treatment mode of patients was analyzed. Cox proportional hazard model was used to analyze the association of the progression-free survival (PFS) time of patients receiving EGFR-TKI treatment with the different types of EGFR mutation, the clinicopathological characteristics, hematological related indexes and treatment mode. Kaplan-Meier method was used to analyze the independent influencing factors for the PFS of the stratified patients.Results:The overall disease control rate (DCR) of patients receiving EGFR-TKI treatment was 92.3% (96/104). Cox univariate analysis showed that the levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), D-dimer, and previous surgical treatment history of patients receiving EGFR-TKI treatment were associated with PFS of patients (all P < 0.05). Cox multi-factor analysis showed that EGFR mutation type ( HR =2.371, 95% CI 1.298-4.332, P = 0.005), combination therapy ( HR = 0.489, 95% CI 0.245-0.978, P = 0.043) and choice of therapeutic drugs ( HR = 0.261, 95% CI 0.113-0.606, P = 0.002) were independent influencing factors for the PFS of patients receiving EGFR-TKI treatment. The PFS of EGFR 19 exon-mutant patients with advanced NSCLC was longer than that of those with EGFR 21 exon-mutant (median PFS time: 14.0 months vs.9.5 months, P<0.05); the PFS of combination of radiotherapy or chemotherapy was longer than that of EGFR-TKI single therapy (median PFS time: 15.0 months vs. 9.0 months, P<0.05), the PFS of patients receiving erlotinib was better than that of those receiving gefitinib ( P<0.05). According to EGFR mutation types, it was found that EGFR 19 exon-mutant patients receiving EGFR-TKI in first-line treatment could obtain better PFS than those who receiving EGFR-TKI in second-line and above treatment (median PFS time: 14.0 months vs. 9.5 months, P<0.05). When receiving EGFR-TKI, EGFR 19 exon-mutant patients with CA125 <85 U/ml could obtain longer PFS time than those with CA125 ≥85 U/ml (median PFS time: 14.0 months vs. 6.5 months, P<0.05). Conclusions:The therapeutic effect of EGFR-TKI in EGFR-mutant patients with advanced NSCLC is positive. EGFR 19 exon-mutant NSCLC patients with low-level CA125 receiving EGFR-TKI in first-line treatment can obtain better PFS.

Therapeutic Effect of PE+CRRT Combined with Chemotherapy on Children with Severe EBV-HLH and Non-EBV-HLH / 中国实验血液学杂志

OBJECTIVE@#To investigate the difference in the therapeutic effect of plasma exchange and continuous renal replacement therapy (PE+CRRT) combined with chemotherapy in the treatment of children with severe Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and non-EBV-HLH.@*METHODS@#The clinical data of 21 cases of all children with severe HLH treated by PE+CRRT combined with chemotherapy from January 2017 to January 2020 were collected and retrospectively analyzed. According to the presence of EBV infection, the children were divided into EBV@*RESULTS@#Among the 21 children, 14 were divided into the EBV@*CONCLUSION@#PE+CRRT combined with chemotherapy can reduce serum ferritin quickly, then improve organ function, and increase the overall survival rate of severe HLH, and it is a good effect on children with severe EBV-HLH and non-EBV-HLH.

Analysis of the relationship between the peripheral blood neutrophil-to-lymphocyte ratio and the mutation types of EGFR in patients with advanced non-small cell lung cancer / 中国基层医药

Objective:To investigate the relationship between neutrophil-to-lymphocyte ratio(NLR) and the type of epidermal growth factor receptor(EGFR) mutation and clinical characteristics in patients with advanced non-small cell lung cancer(NSCLC).Methods:From January 2017 to July 2019, the hematological detection, gene detection and clinical characteristics of 192 EGFR-mutant patients of advanced NSCLC in the Second Hospital of Wuxi Affiliated to Nanjing Medical University were collected and reviewed.The peripheral blood NLR and clinical characteristics in patients with different types of EGFR mutation.(including exon 19 and 21 mutation) were compared.Results:In this study, there were 192 NSCLC patients with EGFR mutation, including 90 patients with EGFR mutation in exon 19(46.87%), aged (67.7±12.8)years old; 84 patients with EGFR mutation in exon 21(43.75%), aged (66.6±9.3)years old; 18 patients with other types of EGFR mutation(9.38%), aged (72.5±10.5)years old.The average age of patients with other types of EGFR mutation was relatively older compared with those in exon 19 or 21 mutation, but there was no statistically significant difference( F=2.90, P>0.05). The patients with EGFR exon 19 mutation were more likely to occur in the right side(48/90) compared with EGFR exon 21 mutation(54/84), and there was statistically significant difference between the two groups(χ 2=5.45, P<0.05). However, the average NLR was (3.98±4.02) in patients with mutation in exons 19, (3.29±1.63) in patients with mutation in exons 21, and (5.32±3.48) in patients with other types of mutations.Compared with the average NLR in exon 21 mutation, the average NLR in patients with non 19 and 21 common mutations was relatively higher, but there was no statistically significant difference( F=3.51, P>0.05). According to the median NLR of 2.9, all cases were divided into two groups: NLR≤2.9 was low NLR group(99 cases), and NLR>2.9 was high NLR group(93 cases). There were statistically significant differences in sex, smoking history, pathological type, eastern cooperative oncology group (ECOG) score, brain metastasis, pleura metastasis and carcinoembryonic antigen(CEA) level between high and low NLR groups(χ 2=4.52, 9.01, 10.05, 9.07, 5.89, 9.03, 19.53, all P<0.05). However, there were no statistically significant differences in age and bone metastasis between high and low NLR groups(χ 2=1.56, 1.51, all P>0.05). Conclusion:Sex, smoking history, pathological type, ECOG score, brain metastasis, pleura metastasis and CEA levels are correlated with NLR level in advanced NSCLC patients.There is certain reference value of the primary focal site in distinguishing EGFR mutation types.However, there is no correlation between NLR level and EGFR mutation type.

Discovery and Verification of Multi-component Chinese Medicine with Anti-tumor Activity from Shuanghuanglian / 中国实验方剂学杂志

Objective:The methods of network pharmacology were adopted to predict Multi-component Chinese Medicine （MCCM） with anti-tumor activity from Shuanghuanglian （SHL）. Furthermore， the pharmaceutical activity of CT26 colon cancer was verified in vitro and in vivo. Method:Based on the Traditional Chinese Medicine Systems Pharmacology Database （TCMSP）， the Handbook of Active Components Analysis of Traditional Chinese Medicine， the Drugbank database， the Reactome database， and the Human protein reference database （HPRD）， the protein-protein interactions network （PPI） and the drug target network were built and resolved. The data was mined to discover the pharmacological effect. The anti- tumor activity of components from SHL was determined based on the nearest distance rule between the compounds and the nodes of network. And then， the anti-tumor effect of the MCCM was verified in vitro and in vivo. Result:The 3 combined compounds， baicalin， forsythoside A and chlorogenic acid with the anti-tumor activity from SHL were predicted and discovered. The verification results showed that the combination of baicalin-forsythoside A-chlorogenic acid could significantly inhibit the cell proliferation and migration compared with the control group in vitro （P<0.01）. Among CT26 bearing mice， the tumor volume and weight were significantly decreased after the combined administration of baicalin-forsythoside A-chlorogenic acid compared with the model group in vivo （P<0.01）. Conclusion:By the methods of network pharmacology， the anti-tumor activities of component of from SHL were discovered. According to the verification in vitro and in vivo， the combination of baicalin-forsythoside A-chlorogenic acid could play better anti-CT26 tumor activity.

Clinical Efficacy of Dahuang Zhuyu Decoction for Oral Administration and Enema on Severe Acute Pancreatitis with Syndromes of Blood Stasis, Toxin and Its Effect on Serum Inflammatory Factors / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of Dahuang Zhuyu decoction for oral administration and enema on severe acute pancreatitis with syndromes of blood stasis and toxin and its effect on serum inflammatory factors. Method::Sixty eight patients with severe acute pancreatitis with syndromes of blood stasis and toxin who were admitted in Henan Provincial People's Hospital from September 2017 to December 2018 were randomly divided into treatment group (34 cases) and control group (34 cases). The control group was treated with western medicine. The treatment group was treated with Dahuang Zhuyu decoction for oral administattion and enema in addition to the therapy of the control group. Both groups were treated for 7 days. Before and after treatment, abdominal pain, bloating, nausea and vomiting were scored separately, serum amylase (AMS), lipase (LPS), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were detected, and abdominal pain disappearance time, bloating disappearance time and exhaust recovery time were recorded. Result::After treatment, the abdominal pain score, abdominal distension score, nausea and vomiting score, serum AMS, LPS, IL-6 and TNF-α were lower than those before treatment (P<0.05), and those in treatment group was lower than those in control group (P<0.05). After treatment, IL-10 level in both groups was higher than those before treatment (P<0.05), and that in treatment group was higher than that in control group (P<0.05). The disappearance time of abdominal pain, the disappearance time of abdominal distension and the recovery time of exhaust were shorter in treatment group than in control group (P<0.05). The total effective rate of the treatment group was higher than that of the control group (P<0.05). Conclusion::Dahuang Zhuyu decoction for oral administration and enema for severe acute pancreatitis with syndromes of blood stasis and toxin can alleviate clinical symptoms, reduce amylase and lipase levels, inhibit the expression of pro-inflammatory factors, promote the expression of anti-inflammatory factors, restore intestinal function, and improve clinical efficacy.

BAX Deletion Accelerates Progression of BCR-ABL-Induced B-ALL in Mice / 中国实验血液学杂志

OBJECTIVE@#To explore whether BAX plays a role in the development of Philadelphia chromosome-positive leukemia and related mechanisms.@*METHODS@#Target-gene knockout mice were used as bone marrow cell donors. Retrovirus over-expressing BCR-ABL were packaged. BCR-ABL-induced B-ALL mouse model was established through donor's B cells transfected by the retrovirus and the B cells over-expressing BCR-ABL were given to the receptor mice by tail vein injection. Western blot was used to detect the protein express and flow cytometry was used to analyze the B cell subpopulations in BAX and WT mouse bone marrows. Kaplan-Meier analysis was used to estimate the survival of diseased mice.@*RESULTS@#BAX deletion caused faster development of BCR-ABL-induced leukemia in vitro and in vivo. BCR-ABL increased BCL-2 expression and enhanced BCL-2/BAX heterodimer formation.@*CONCLUSION@#The BAX deletion can accelerate the disease progression of BCR-ABL induced B-ALL.

Expression of DDX46 protein in colorectal cancer and its correlation with expressions of C-erbB-2, Ki-67, p53 and nm23 proteins / 肿瘤研究与临床

Objective To investigate the expression of DDX46 protein in colorectal cancer and its correlation with expressions of C-erbB-2, Ki-67, p53 and nm23 proteins. Methods A total of 149 cases of colorectal cancer tissues and 45 adjacent mucosa tissues after operation in the Wuxi No.2 Hospital Affiliated to Nanjing Medical University from January 2010 to December 2012 were collected. The expressions of DDX46 protein and C-erbB-2, Ki-67, p53 and nm23 proteins in tissues of colorectal cancer were detected by using immunohistochemistry. The relations between the expression level of DDX46 protein and the clinicopathological features including the age, gender, tumor differentiation, tumor infiltration, lymph node metastasis, TNM stage were analyzed, and the relations between DDX46 protein expression and expressions of C-erbB-2, Ki-67, p53 and nm23 proteins were also analyzed. Results Of 149 colorectal cancer tissues, 50 (33.6％) showed low expressions of DDX46 protein and 99 (66.4％) showed high expressions. Of 45 adjacent mucosa tissues, 37 (82.2％) showed low expressions of DDX46 protein, and 8 (17.8％) showed high expressions. There were significant differences between the high expression rate of DDX46 protein in cancer tissues and adjacent mucosa tissues (χ2=33.09, P<0.01). There were statistical differences in the expression level of DDX46 protein and tumor differentiation, tumor infiltration, lymph node metastasis, TNM staging (all P<0.05). The ratio of high-expressed DDX46 protein was increased with the low differentiation, high invasion degree, lymph node metastasis and late TNM staging. DDX46 protein expression was correlated with expressions of Ki-67, p53 and nm23 proteins (all P< 0.05), and the expression of DDX46 protein had a positive correlation with expressions of Ki-67 and p53 proteins (r values were 0.161 and 0.347), and a negative correlation with expression of nm23 protein (r= -0.561). Conclusions The high expression of DDX46 protein in colorectal cancer tissues is related with malignant biological behavior of the tumors and the key oncogenes. DDX46 protein could be regarded as the potential marker for the diagnosis and molecular targeting therapy of colorectal cancer.

Induction of Endoplasmic Reticulum Stress by Cadmium and Its Regulation on Nrf2 Signaling Pathway in Kidneys of Rats / 生物医学与环境科学（英文）

OBJECTIVE@#This study was conducted to investigate the regulation of endoplasmic reticulum stress on Nrf2 signaling pathway in the kidneys of rats.@*METHODS@#Rats were divided into twelve groups of six animals each. Some groups were pre-administered with bacitracin or tauroursodeoxycholic acid (TUDCA), and all of them were treated with 5-20 μmol/kg cadmium (Cd) for 48 h. The oxidative stress levels were analyzed using kits. The mRNA and protein expression levels of endoplasmic reticulum stress-related factors and Nrf2 signaling pathway-related factors were determined using RT-PCR and western blot.@*RESULTS@#Cd exposure resulted in oxidative stress in the kidneys of rats and upregulated the expression of endoplasmic reticulum stress (ERS)-related factors and Nrf2 signaling pathway-related factors, especially at doses of 10 and 20 μmol/kg Cd, and the expression changes were particularly obvious. Moreover, after pretreatment with bacitracin, Cd upregulated the expression of ERS-related factors to a certain extent and, at higher doses, increased the mRNA expression of Nrf2. After pretreatment with TUDCA, Cd reduced the level of ERS to a certain extent; however, at these doses, there were no significant changes in the expression of Nrf2.@*CONCLUSION@#Cadmium can result in ERS and oxidative stress in the kidneys of rats, activate Nrf2, and upregulate the transcriptional expression of phase II detoxification enzymes under these experimental conditions. ERS has a positive regulation effect on Nrf2 signaling pathway but has little effect on the negative regulation of Nrf2 signaling pathway in cadmium toxicity.

Practice and thinking on precise quality control management of radiotherapy of cancer hospital based on patient safety / 中华放射肿瘤学杂志

Patient safety is the foundation of the hospital management. In recent years, Department of Radiation Oncology of Jiangsu Cancer Hospital has attached great importance to patient safety by introducing the precise concept to the quality control and management of radiotherapy, which includes pursuing standardized construction of quality control, accurately identifying the patients, combination of process reengineering and informatization, departmental learning and multi-disciplinary integration and paying attention to performance assessment. All these measures significantly elevate the medical quality and patient safety.

Practice and thinking on precise quality control management of radiotherapy of cancer hospital based on patient safety / 中华放射肿瘤学杂志

Patient safety is the foundation of the hospital management.In recent years,Department of Radiation Oncology of Jiangsu Cancer Hospital has attached great importance to patient safety by introducing the precise concept to the quality control and management of radiotherapy,which includes pursuing standardized construction of quality control,accurately identifying the patients,combination of process reengineering and informatization,departmental learning and multi-disciplinary integration and paying attention to performance assessment.All these measures significantly elevate the medical quality and patient safety.

Application of Intermittent Lung Inflation Combined with Rigid Ureteroscopy in Treating Upper Ureteral Stones That Were Not Fully Visible / 中国医学科学院学报

To analyze the effectiveness and safety of intermittent lung inflation combined with rigid ureteroscopy in the treatment of upper ureteral stones that were not fully visible. The clinical and imaging data of 56 patients with upper ureteral stone undergoing rigid ureteroscopic lithotripsy combined with intermittent lung inflation in Zhejiang Quhua Hospital from March 2016 to October 2017 were retrospectively analyzed.Intermittentt lung inflation was used to change and stabilize the position of ureteral calculi during the operation,so as to ensure the visual field of ureteroscopy.Holmium laser lithotripsy was performed to remove the stones.Urinary tract abdominal plain X-ray or CT urography was performed 1 and 3 months after the operation to evaluate the residual stones and the clinical efficacy. Stones were successfully removed after a single attempt in 48 patients.In 5 patients,stones escaped into the kidney during ureteroscopic lithotripsy,and thus flexible ureteroscopy were performed.In 3 patients,a second session of auxiliary procedure was required,among whom 2 patients received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy+ureteroscopic lithotripsy.The stone-free rates 1 and 3 months after surgery were 94.6%(53/56)and 100%(56/56),respectively.No severe complication such as ureter perforation,gross hematuria,septic shock,or pneumothorax occurred during and after surgery. Intermittent lung inflation in tracheal intubation under general anesthesia in patients with proximal ureteral stones that can not be fully visible during rigid ureteroscopic lithotripsy was feasible and reliable.It can effectively change the location of stones and thus enable safe and effective lithotripy.It expands the indications of rigid ureteroscopy for treating upper ureteral stones.

BAX Gene Deletion Reduces the Sensitivity of BCR-ABL-Induced B-ALL Cells of Mice to Imatinib / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of BAX gene deletion on the sensitivity of BCR-ABL-induced B-ALL cells of mice to imatinib and the related mechanism.@*METHODS@#The target gene-knock out (BAX) mice were used as bone marrow cell donors; the wild type bone marrow cells(B6BM) and BAX bone marrow cells(B6BM-BAX) of mice were transfected by using reverse transcription virus, then the BCR-ABL transfected B6BM cells and B6BM-BAX cells were treated with imatinib at different concentration (0,0.5, 1.0 and 2.0 μmol/L) for 48 hours. The number of viable cells was detected by trypan blue, the flow cytometry was used to detect the cell apoptosis, the Western blot was used to detect the changes of BAX, Caspase expression.@*RESULTS@#In BCR-ABL transfected bone marrow cells treated with imatinib, the numbers of viable cells of BAX deletion group was significantly higher than that of wild type groups with statristcal difference(P<0.05), and effect- and dose-dependency(r=-0.9533 for BAX deletion group, and r=-0.9812 for wild type group). The flow cytometry showed that the cell apoptosis in BAX deletion group signifincantly decreased, compared with wild type group(P<0.05). The Western blot showed that the expression of apoptotic protein Caspase 3 in BAX deletion group was significantly higher than that in wild type group(P<0.05).@*CONCLUSION@#BAX deletion can reduce the sensitivity of BCR-ABL-induced B-ALL cells to imatinib.

Functional Connectivity-Based Modelling Simulates Subject-Specific Network Spreading Effects of Focal Brain Stimulation / 神经科学通报·英文版

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson's disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson's Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.

Effects of DDX46 gene on the radiosensitivity of colorectal cancer cells / 中华放射医学与防护杂志

Objective To investigate the effect of DDX46 gene on the radiosensitivity of colorectal cancer cells and underlying mechanism.Methods SW480 cells transfected with DDX46 RNAi or its empty plasmid by lentivirus were set as experimental group and control group,respectively.After 72 h of transfection,the cells were irradiated with 4 Gy X rays.The cell viabilities of these two groups were detected by CCK-8 assay.The number of γ-H2AX foci and the expressions of some key proteins related to DNA damage repair were detected by immunofluorescence technique and Western blot at 24 h after irradiation.Results At 24 h after 4 Gy irradiation,the cell vitality of experimental group was decreased to (15.02±3.92)％(t=-4.696,P ＜ 0.05) of control and(17.43 ±1.83)％(t=4.844,P＜0.01) of nonirradiated cells,but there was no significant difference between 4 Gy irradiated control cells and nonirradiated cells.Meanwhile,compared with the control group,the ATM protein expression level (t =7.530,P ＜0.01) and the number of γ-H2AX foci (t =-3.108,P ＜0.05) were significantly increased in the experimental SW480 cells,while the expression levels of p-ATM and Rad50 were significantly reduced (t =4.260,4.260,P ＜ 0.05),and the protein levels of DNA-PK in these two groups had tiny difference.Conclusions DDX46 RNA silence increases the radiation sensitivity of SW480 cells by inhibiting ATM activation and DNA repair.

Practice and consideration of hospital′s discipline system construction based on discipline tree cultivation strategy / 中华医院管理杂志

A review is made on the hospital′s practices in discipline tree cultivation strategy. These approaches include contests in disciplinary development, encouragement of technology innovation, optimizing talents echelons, strengthening team learning, advocating medical translation, and setting up disciplinary construction management cycle among others. The authors proposed to insist in the principles of justice and equity, parallel development of technology and management for discipline leaders, development within capabilities, and upholding both inheritance and innovation.

Construction and consideration of hospital services continuous improvement based on patients ' experience / 中国基层医药

Patients' experience is the feeling of patients in the process of medical perception. This paper expounded the new concept based on the experience of patients with medical services,then reviewed the specific practices of improve services,which including three - dimensional registration service,process intensification,service public commitment, patients choose doctors in medico - technical departments, hospital president in outpatient. Finally,the article proposed that patients' experience should be based on patients' evaluation,have " love" heart, exceed customers' expectation and build patients' experience culture.

Preliminary exploration on state-owned capital in the reform of state-owned corporate hospitals / 中华医院管理杂志

State-owned capital not only had the social public welfare characteristic, but also the vitality and driving force of capital. In this research, Zhejiang Medical and Health Group was studied based on analyzing questions of state-owned corporate hospitals. We also introduced practice and effectiveness of state-owned capital in the reform of 3 state-owned corporate hospitals in this group. This paper aimed to explore a new way for state-owned capital to participate in public hospital reform. At the same time, it also provided suggestions for the transformation and development of state-owned corporate hospitals.

Combination of musk and olibanum promotes proliferation of prostate stem cells in mice: An experimental study / 中华男科学杂志

Objective@#To study the effects of muskolibanum combination on the proliferation and differentiation of prostate stem cells.@*METHODS@#We cultured prostate epithelial cells and urogenital sinus mesenchymal (UGSM) cells from 7－10 d old C57BL/6 mice and 16－18 d old pregnant C57BL/6 mice, transplanted the mixed suspension of the two types of cells under the kidney envelope of SCIDCB.17 male mice, and harvested the transplants 30 days later. We randomly divided the SCIDCB.17 mice into four groups to be treated intragastrically with musk (n = 8), olibanum (n = 8), musk+olibanum (n = 7), and normal saline (blank control, n = 8)) respectively, all for 14 days. Then we collected the kidney tissue for observation of the morphology of the glandular tubes and differentiation of different subsets of stem cells by HE staining and determination of the expressions and distribution of P63, CD133, CD117 and Sca1 by immunohistochemistry and Western blot.@*RESULTS@#A system was successfully established for the isolation and mixed culture of Sca1 Lin+ CD49f+ (LSC) cells of prostate stem cells and UGSM cells of the mouse embryonic prostate. Immunohistochemistry showed positive expressions of P63, CD133, Sca1, and CD117 in the prostatic acinar epithelia and proved the presence of prostatic acinar epithelial structure in the transplants. Compared with the blank control group, the expressions of CD133, Sca1 and CD117 were significantly increased in the musk, olibanum, and musk+olibanum groups (P< 0.05), higher in the musk+olibanum than in the musk or olibanum group (P< 0.05), and their protein expressions were even more elevated in the musk+olibanum group (P< 0.01), with statistically significant difference from the olibanum group (P< 0.05).@*CONCLUSIONS@#The combination of musk and olibanum can improve the proliferation and differentiation of prostate stem cells.