ObjectiveTo explore the effect of targeted intervention measures based on risk score of venous thromboembolism （VTE）， on the prevention of senile type 2 diabetes inpatients， as well as their influence on the occurrence of venous thromboembolism. MethodsA total of 134 elderly patients with type 2 diabetes mellitus who were hospitalized in geriatrics department of Peking university third hospital during June 1， 2018 to September 30， 2018 were selected as the research subjects. All the patients were divided into control group and observation group according to random number table method， with 67 patients in each group. Patients in the control group were treated with conventional intervention methods， and patients in the observation group were treated with targeted intervention measures based on VTE risk score. After one month of intervention， the Padua score， blood glucose level and coagulation indexes of the two groups were compared. The incidence of thrombosis during the intervention period was also recorded. ResultsThe Padua score in observation group （2.09±2.17） points was significantly lower than that （3.19±2.37） points in control group （P<0.05）. The indexes of fasting blood glucose， 2h postprandial blood glucose and HbA1c in observation group were significantly lower than those in control group （P<0.05）. The fibrinogen， D-dimer， activated partial thromboplastin time and prothrombin time in observation group were significantly lower than those in control group （P<0.05）. The incidence of DVT， PVT， lower limb swelling， pain and abnormal skin color in the observation group were 4.00%， 2.00%， 2.00%， 2.00%， and 0， respectively， and in the control group were 12.00%， 10.00%， 10.00%， 12.00%， and 8.00%， respectively. The incidence of adverse events in observation group was significantly lower than that in control group （P<0.05）. ConclusionTargeted intervention based on VTE risk score can significantly reduce the risk of VTE occurrence， improve blood clotting function and blood glucose level in elderly patients with type 2 diabetes mellitus. This nursing measure has important clinical application value.

Objective:To explore the influence of tomoxetine hydrochloride on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods:From January 2018 to July 2021, 62 ADHD children who were treated with tomoxetine hydrochloride for the first time for(8±4) weeks were selected as the ADHD group.And 62 healthy children matched with age and sex were selected as the healthy control group.Pre-test and post-test by the Das-Naglieri: Cognitive Assessment System(DN: CAS) were performed to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group were compared with those in healthy control group.The difference between before and after treatment of ADHD group was also compared.SPSS 26.0 statistical software was adopted for statistical analysis.The scores of ADHD group pre-treatment and post-treatment were compared by paired sample t-test, and the scores of ADHD group pre-treatment and post-treatment were compared with those of healthy control group by independent sample t-test. Results:Compared with healthy control group, there were lower of planning score((18.77±5.92) vs (28.56±5.55)), attention score((22.24±5.93) vs (29.56±6.16)), simultaneous processing ((34.21±7.75) vs (37.61±6.29)), successive processing((30.37±7.12) vs (33.74±5.43)), and the total scores((105.60±21.29) vs (134.84±22.87)) in ADHD group before treatment, and there were significant differences( t=9.49, 6.74, 2.68, 2.96, 7.36, all P<0.05). Compared with healthy control group, there were lower of planning score ((22.13±5.99)s), attention score((25.26±7.11) with significant difference( t=6.20, 3.60, both P<0.05) in ADHD group after treatment.And there was no significant difference in the simultaneous processing test and the successive processing test after treatment compared with the healthy control group(both P>0.05). In ADHD group, the scores of planning, simultaneous processing, attention, successive processing and the total score were significantly higher after treatment than those before treatment and there were significant differences( t=-6.03, -4.13, -4.77, -5.48, -8.59, all P<0.05). (2) Compared with the healthy control group, there were lower of matching number score and other 8 sub-test scales in DN: CAS test in ADHD group before treatment, and the differences were statistically significant (all P<0.05). Meanwhile, there were still lower of matching number score and other 4 sub-test scales in DN: CAS test in ADHD group after treatment, and the differences were statistically significant (all P<0.05). The matching number score and other 10 sub-test scales in DN: CAS test in ADHD group after treatment were all higher than those of before treatment(all P<0.05). Conclusion:The planning, attention, simultaneous processing, successive processing and total cognitive function of ADHD children were significantly improved after treatment with tomoxetine hydrochloride, special for simultaneous processing and successive processing.

Objective:To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) .Methods:Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology. Flow cytometry was used to detect the effects of knockdown of PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in AMKL cells.Results:PAK1 inhibitors inhibited the proliferation of AMKL cells in a dose-dependent manner and reduced the ability of cell colony formation, and the difference was statistically significant when compared with the control group ( P<0.05) . Moreover, they also reduced the percentage of AMKL cells in S phase, and Western blot detection showed that the expression levels of phosphorylated PAK1 and cyclin D1 decreased significantly. Finally, PAK1 inhibitors induced AMKL cell apoptosis by up-regulating Cleaved caspase 3 and showed different abilities to increase the content of polyploid DNA in megakaryocytes. Only high concentrations of IPA-3 and low doses of G5555 increased the number of polyploid megakaryocytes, while knockdown of PAK1 kinase activity promoted AMKL cell differentiation and increased the apoptosis rate. Conclusion:PAK1 inhibitor significantly arrests AMKL cell growth and promotes cell apoptosis. Knocking down the expression of PAK1 promotes the formation of polyploid DNA and induces AMKL cell apoptosis. The above findings indicate that inhibiting the activity of PAK1 may control AMKL effectively.

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Objective To investigate the clinical value of liquid-based cytology and cell paraffin blocks combined with immu-nocytochemical examination in cytopathologic diagnosis of hydrothorax and ascites.Methods One hundred and fourteen cases of hydrothorax and ascites sample were collected.The detection positive rates were compared between the liquid-based cytology and cell paraffin blocks combined with immunocyochemical examination.The suspected positive and positive cases were performed the immunocytochemical examination for further judging benign and malignancy and histological source.Results 114 cases of hydro-thorax and ascites samples,36 cases(31.58%)of positive were diagnosed by liquid-based cytologyamong and 55 cases(48.24%)of positive were diagnosed by cell paraffin blocks combined with immunocytochemical examination,the difference was statistically sig-nificant(P<0.01).There were 55 cases of malignant hydrothorax and ascites,45 cases were hydrothorax and 10 cases were ascites, in hydrothorax,there were 32 cases of lung adenocarcinoma,3 cases of small cell lung cancer,4 cases of breast cancer,1 case of en-dometrial carcinoma,1 case of lymphatic hematopoietic system tumor and 4 cases of unknown origin;in ascites,there were 2 cases of ovarian cancer,1 case of digestive system tumor,1 case of endometrial cancer,1 case of lymphatic hematopoietic system tumor and 5 cases of unknown origin.Conclusion The cell paraffin blocks combined with immunocytochemistry can significantly improve the positive detection rate of hydrothorax and ascites,and helps to judge the source of tissue.

Objective To evaluate the effects of penehyclidine hydrochloride (PHCD) combined with high-frequency jet ventilation (HFJV) of the operated lungs on pulmonary function and inflammatory response during one-lung ventilation (OLV) in patients with chronic obstructive pulmonary disease (COPD).Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes with COPD,aged 40-64 yr,with body mass index of 17-26 kg/m2,scheduled for elective video-assisted thoracoscopic surgery under general anesthesia,were divided into 4 groups (n =15 each) using a random number table method:conventional group (group C),PHCD group (group P),HFJV group (group H) and PHCD combined with HFJV group (group PH).After induction of anesthesia,the patients were intubated with a double-lumen tube and then mechanically ventilated,with inspired oxygen concentration 100％,oxygen flow rate 2 L/min,tidal volume 6-8 ml/kg,respiratory rate 10-14 breaths/min,and respiratory rate was set at 12-16 breaths/min and PETCO2 was maintained at 40-45 mmHg during OLV.PHCD 0.01 mg/kg was intravenously injected before intubation in P and PH groups.The ventilation mode was changed to OLV after beginning of skin incision in each group.Ventilation of the lung on the operated side was performed by means of HFJV (driving pressure 0.5 kg/cm2) during OLV in P and PH groups.The pneumodynamic parameters such as airway peak pressure (Ppeak),airway plateau pressure (Pplat),airway resistance (Raw) and dynamic lung compliance (Cdyn) were monitored immediately before skin incision (T1) and at 60 and 120 min of OLV (T2,3).Arterial blood samples were obtained at T2 for blood gas analysis,and oxygenation index (OI),respiratory index (RI),physiologic dead space fraction (VD/Vr)and alveolar-arterial oxygen gradiant (A-aDO2) were calculated.Venous blood samples were drawn at T3 for determination of the serum concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6)and IL-8 by enzyme-linked immunosorbent assay.The occurrence of pulmonary complications was recorded within 72 h after operation.Results Compared with group C,the serum concentrations of TNF-α,IL-6 and IL-8,Ppeak,Pplat,Raw,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and Cdyn and OI were increased in group P and group PH (P＜0.05),and the serum concentrations of TNF-α,IL-6 and IL-8,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and OI was increased in group H (P＜0.05).Compared with group P or group H,the serum concentrations of TNF-α,IL-6 and IL-8,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and OI was increased in group PH (P＜0.05).Conclusion PHCD combined with HFJV of the operated lung produces better efficacy in improving respiratory function,inhibiting inflammatory responses,reducing lung injury and is more helpful in improving prognosis than either alone in the patients with COPD.

Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
Animals ; Apoptosis ; Cause of Death ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Repression, Psychology ; RNA, Small Interfering

Objective To explore the influence of Methylphenidate Hydrochloride prolonged-release tablets on the cognitive processing of children with attention deficit hyperactivity disorder (ADHD).Methods Thirty ADHD children and 30 healthy controls were enrolled in this study,and the ADHD subjects were treated with Methylphenidate Hydrochloride prolonged-release tablets for (28 ± 3) days.Pre-test and post-test by the Das-Naglieri:Cognitive Assessment System(DN:CAS) were done to evaluate the cognitive function of all individuals.The differences of cognitive processing in pre-treatment and post-treatment of ADHD group with healthy control group were compared.The difference between before and after treatment of ADHD was also compared.Results Compared with healthy control group,there were lower of planning score [(21.86 ± 4.61) scores vs.(29.33 ± 5.06) scores],attention score [(25.00 ± 4.57) scores vs.(29.83 ± 3.79) scores],and the total scores [(111.93 ± 13.95) scores vs.(127.26 ±15.53) scores] in ADHD group,and there were significant differences (t =-5.976,-4.455,-4.023,all P ＜0.05).The matching number,planned codes,planned connections,expressive attention,number detection and receptive attention scores were also lower in ADHD group,and there were significant differences (t =-4.787,-3.703,-4.991,-2.216,-2.488,-3.219,all P ＜ 0.05).Compared with healthy control group,there were lower of planning score with significant difference [(25.53 ± 4.98) scores vs.(29.33 ± 5.06) scores,t =-2.931,P ＜ 0.05] in ADHD group after treatment,matching number and planned codes were lower with significant difference (t =-2.654,-2.044,all P ＜ 0.05) in ADHD group after treatment.In ADHD group,the scores of planning [(25.53 ± 4.98)scores vs.(21.86 ± 4.61) scores],simultaneous processing [(36.10 ± 7.10) scores vs.(34.13 ± 6.04) scores],attention [(27.90 ± 5.69) scores vs.(25.00 ± 4.57) scores] and the total score [(121.50 ± 16.55) scores vs.(111.93 ± 13.95) scores] were significantly higher after treatment than that before treatment and there were significant differences (t =-5.679,-2.949,-3.869,-5.963,all P ＜ 0.05);matching number,planned codes,planned connections,nonverbal matrices,number detection,receptive attention and word series were significantly higher after treatment than that before treatment,and there were significant differences (t =-2.528,-3.209,-3.890,-2.276,-4.489,-2.208,-2.373,all P ＜ 0.05).Conclusion The Methylphenidate Hydrochloride prolonged-release tablets can improve the function of cognitive processing in children with ADHD,especially in attention.

Objective To investigate the efficacy of zoledronic acid in the treatment of senile unstable femoral intertrochanteric fractures with anatomical locking plate. Methods 67 patients were randomly divided into two groups. Five days after the operation, group A received one intravenous injection of 5 mg zoledronic acid, while patients in group B did not receive the injection. The two groups were compared in terms of hospitalization time, complications, limb weight-bearing time, fracture healing time, hip function score after operation, preoperative and postoperative serum calcium and serum ALP, bone mineral density of proximal femur before operation and 1 year after operation. Results There were no statistically significant differences between the two groups in age, type of fracture, hospital stay, partial weight-bearing time, fracture healing time, hip function at 1 month and 1 year after operation, preoperative bone mineral density and blood calcium. But the differences were statistically different in hip function at 3 months after operation , averaged bone mineral density of proximal femur and serum ALP 1 year after operation. Moreover, 5 patients in group A developed muscle pain or fever after intravenous injection of zoledronic acid. Conclusion The locking plate combined with zoledronic acid injection in treatment of elderly patients with unstable femoral intertrochanteric fracture could inhibit bone loss, increase bone mineral density, and accelerate limb function recovery after operation. On the other hand, Zoledronic acid has a high incidence of adverse reaction.