Mechanism of nuclear protein 1 in the resistance to axitinib in clear cell renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients.@*METHODS@#By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance.@*RESULTS@#Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib.@*CONCLUSION@#ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.

Exploration of centralized closed-loop management mode for gynecological day surgery / 中华医院管理杂志

Day surgery can effectively improve the utilization of medical resources. In October 2015, an obstetrics and gynecology hospital established a gynecological day surgery center to centrally manage gynecological day surgery and continuously optimize the management process. In July 2019, the hospital established an intelligent information platform for gynecological daytime surgery managemen. Based on this platform, the " evaluation-appointment-hospitalization-follow-up-chronic disease management" information management process was implemented, the " pre hospital-in hospital-post hospital" full process medical quality and safety monitoring was carried out to form a centralized closed-loop management mode for gynecological day surgery led by gynecologists. Under this management mode, the number of gynecological day surgeries in the hospital has increased from 2 866 cases in 2019 to 4 065 cases in 2021, providing convenient medical services and personalized chronic disease management services, and ensuring the quality and safety of gynecological day medical care, for reference for promoting the high-quality development of day surgeries in specialized hospitals.

Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL).@*METHODS@#Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits.@*RESULTS@#It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated.@*CONCLUSION@#Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Early efficacy of three dimensional printed anatomical biomimetic cervical artificial disc replacement in the treatment of cervical degenerative diseases / 中华外科杂志

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C3－4 level in 2 cases, C4－5 level in 5 cases, C5－6 level in 9 cases, and C6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.

Effect of porous zirconia ceramics on proliferation and differentiation of osteoblasts / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of porous surface morphology of zirconia on the proliferation and differentiation of osteoblasts.@*METHODS@#According to different manufacturing and pore-forming methods, the zirconia specimens were divided into 4 groups, including milled sintering group (M-Ctrl), milled porous group (M-Porous), 3D printed sintering group (3D-Ctrl) and 3D printed porous group (3D-Porous). The surface micromorphology, surface roughness, contact angle and surface elements of specimens in each group were detected by scanning electron microscope (SEM), 3D laser microscope, contact angle measuring device and energy-dispersion X-ray analysis, respectively. MC3T3-E1 cells were cultured on 4 groups of zirconia discs. The cell morphology of MC3T3-E1 cells on zirconia discs was eva-luated on 1 and 7 days by SEM. The cell proliferation was detected on 1, 3 and 5 days by cell counting kit-8 (CCK-8). After osteogenic induction for 14 days, the relative mRNA expression of alkaline phosphatase (ALP), type Ⅰ collagen (Colla1), Runt-related transcription factor-2 (Runx2) and osteocalcin (OCN) in MC3T3-E1 cells were detected by real-time quantitative polymerase chain reaction.@*RESULTS@#The pore size [(419.72±6.99) μm] and pore depth [(560.38±8.55) μm] of 3D-Porous group were significantly larger than the pore size [(300.55±155.65) μm] and pore depth [(69.97±31.38) μm] of M-Porous group (P < 0.05). The surface of 3D-Porous group appeared with more regular round pores than that of M-Porous group. The contact angles of all the groups were less than 90°. The contact angles of 3D-Ctrl (73.83°±5.34°) and M-Porous group (72.7°±2.72°) were the largest, with no significant difference between them (P>0.05). Cells adhered inside the pores in M-Porous and 3D-Porous groups, and the proliferation activities of them were significantly higher than those of M-Ctrl and 3D-Ctrl groups after 3 and 5 days' culture (P < 0.05). After 14 days' incubation, ALP, Colla1, Runx2 and OCN mRNA expression in 3D-Porous groups were significantly lower than those of M-Ctrl and 3D-Ctrl groups (P < 0.05). Colla1, Runx2 and OCN mRNA expressions in M-Porous group were higher than those of 3D-Porous group (P < 0.05).@*CONCLUSION@#The porous surface morphology of zirconia can promote the proliferation and adhesion but inhibit the differentiation of MC3T3-E1 cells.

Liposomal melatonin dry powder inhalers for the treatment of primary lung cancer / 药学学报

Melatonin (MLT) is an endogenous chemical that has antitumor effects at high doses. However, it shows low oral bioavailability and short in vivo half-life, leading to drug resistance. Here, liposomal melatonin dry powder inhalers (LMD) were prepared, and were used for treatment of primary rat lung cancer by pulmonary delivery. Liposomal melatonin (LM) was prepared by the ethanol injection method to achieve an entrapment efficiency of 98.89%. LMD was obtained by freeze-drying after LM was mixed with mannitol. LMD appeared as spherical particles under a scanning electron microscope. The rehydrated liposomes had a small size of 65.15 nm and the zeta potential of -14.2 mV without change inentrapment efficiency. LMD had an aerodynamic particle size of 6.73 ± 0.012 μm and a fine particle fraction (FPF<8.06 μm) of 22.2%, suitable for pulmonary delivery. When administered with the same dose, LMD showed much higher inhibition on A549 lung cancer cells than MLT and gemcitabine. LMD of a large dose had no effect on the growth of normal lung epithelial cells (BEAS-2B). Rat lung cancer models were established after 45 days by instilling 3-methylcholanthrene (MCA) and N,N-dimethylnitrosamine (DEN) into the rat lungs once (the experiments had been approved by the ethics committee and carried out in accordance with relevant guidelines and regulations). Decreases of tumor nodules and inflammatory cells in the tumor-bearing rat lungs were observed after treatment of MLT, gemcitabine and LMD by pulmonary delivery compared with the models, wherein LMD was most effective. The efficiencies of inhibition of NF-κB p65, increase of Tunel detection (indicating enhancement of apoptosis), and decrease of malondialdehyde corresponded to LMD being most effective. Therefore, given the fact that LMD can deliver the drug into the tumor tissues of lungs, and it presents as a promising pulmonary inhalable regiment for treatment of lung cancer.

Clinicopathological analysis of patients with papillary renal cell carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features,treatment and prognosis of patients with papillary renal cell carcinoma (PRCC) and PRCC-complicated with tumor thrombus.@*METHODS@#Single center retrospective analysis of 75 patients with PRCC treated from January 2012 to October 2017 was performed. There were 55 males and 20 females at an age range of 24-82 years. Sixteen PRCC patients were complicated with tumor thrombus. All the patients were with a surgery and had clear pathological diagnosis and detailed follow-up data. The clinicopathological features, prognosis and influencing factors of the patients with PRCC and PRCC complicated with tumor thrombus were analyzed and summarized.@*RESULTS@#The average age of the 75 patients was(56.05±11.59)years,the average body mass index (BMI) was (26±3) kg/m², and the average tumor maximum diameter was (5.17±3.85) cm. There were significant differences between tumor maximum diameter larger than 7 cm and less than 7 cm (69.6% vs. 94.4%, P<0.001), lymph node metastasis and no lymph node metastasis (<38% vs. 98%, P<0.001), adrenal metastasis and no adrenal metastasis (0% vs. 95.3%, P<0.001), pulmonary metastasis and no pulmonary metastasis (0% vs.90.7%, P<0.001), complicated with and without tumor thrombus (<66.4% vs. 93.5%, P<0.001) on the effect of 3-year survival rate of the PRCC patients. In this study, there were 16 patients with type 2 PRCC complicated with tumor thrombus. There were significant differences in concomitant symptoms (62.5% vs. 22.0%, P=0.005), maximum tumor diameter (68.8% vs.13.3%, P<0.001), adrenal metastasis (18.8% vs. 0.02%, P=0.029), pulmonary metastasis (18.8% vs. 0%, P=0.008), nuclear grade (P<0.001) and pathological type (100% vs. 44.1%, P<0.001) between the PRCC patients with and without tumor thrombus.@*CONCLUSION@#There were significant differences in tumor diameter,lymph node metastasis,adrenal metastasis, pulmonary metastasis,pathological type, nuclear grade and tumor thrombus in the effect of the 3-year survival rate of PRCC patients. PRCC patients with tumor thrombus were more commonly suffered from type 2 PRCC, for whom the tumor diameter was larger,the nuclear grade was higher,and the distance metastasis happened more easily.

An analysis on the association between sleep quality and dietary behaviors among college students / 预防医学

Objective To examine the effect of eating behavior and dietary intake on the sleep quality of college students,and to provide basis for improving students' sleep quality.Methods College students from Hangzhou Normal University were randomly selected and they were investigated from October to November,2014.Pittsburgh Sleep Quality Index (PSQI) was used to measure the quality of sleep,and a self-designed questionnaire was used to measure eating behavior and dietary intake.Results A total of 588 college students were investigated.The average score of PSQI was 4.72 ±2.52,and 76 (12.9％) of the respondents have poor sleep quality.Single-factor analyses showed that sleep quality was not associated with gender,BMI,cigarette smoking and academic pressure,but was associated with peer effect,meal regularity,and frequency of fish and poultry intake (P ＜ 0.05).Multi-factor logistic regression showed that frequency of eating-out (OR =3.04,95％ CI:1.58-5.84;P =0.001,4 or more than 4 times vs.less than once per week) irregular dinner (OR =1.96,95％ CI:1.23-3.40;P =0.017,irregular vs.regular) and less fish intake (OR =2.48,95％ CI:1.27-4.85;P =0.01,less than once vs.2-3 times per week) increased the risk of poor sleep quality.Conclusion Eating behavior and dietary intake are closely related to sleep quality of college students and they should concern about meal regularity and nutrition balance.

Effect of dexmedetomidine on stress response during tracheal intubation in patients with ICU / 药物评价研究

Objective To investigate the effect of dexmedetomidine on tracheal intubation in patients with ICU.Methods A total of 76 severe cases of patients treated in ICU of Kunming General Hospital of Chinese PLA from January 2015 to January 2016 were selected as the subjects,randomly divided into control and observation groups,38 cases in each group.The two groups underwent radial artery puncture before the trachea intubation,and the venous passage was established.The observation group received iv infusion of dexmedetomidine hydrochloride (0.5 g/kg) for 10 min,and the control group received iv injection of normal saline.Then the two groups were given iv infusion of appropriate atracurium and propofol.The anesthesia dosages of two groups were observed;The levels of angiosthenia (MAP),heart rate (HR) and plasma corticosterone were detected before intubation (T1),after intubation (T2),3 min after intubation (T3) and 5 min after intubation (T4) in two groups.Results Propofol and CIS atracurium anesthesia dose of the two groups had no significant difference.The levels of MAP,HR and plasma corticosterone in observation group were significantly lower than those in the control group at T4 and T3 time (P ＜ 0.05).Conclusion Application of dexmedetomidine anesthesia could reduce the stress response in patients with endotracheal intubation in ICU and maintain stable hemodynamics and plasma corticosterone.

Establishment of submandibular gland allotransplantation model in miniature swine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Autologous transplantation of the submandibular gland (SMG) into the temporal fossa with microvascular anastomosis has been successfully applied in severe xerophthalmia patients as a permanent tear substitute. However, severe xerophthalmia can be accompanied by salivary gland dysfunction, making such autotransplantation unsuitable. Therefore, SMG allotransplantation might be a solution. The aim of this study was to assess the technical feasibility of submandibular gland allotransplantation.</p><p><b>METHODS</b>Twelve miniature swine were randomized to serve as donors or recipients. One SMG was transplanted between a donor and a recipient. The donor SMG was revascularized by microvascular anastomosis of its vascular pedicle to the recipient lingual artery and external jugular vein. The secretory duct was implanted into the vestibule of the mouth through a subcutaneous tunnel. No immunosuppressive agent was administered. The results were assessed by visual inspection of the secretion, and histopathological examination of the transplanted SMG.</p><p><b>RESULTS</b>Technically, all surgical procedures were successful. Clear secretion flowed out of the duct as soon as blood supply of the transplanted submandibular gland was reestablished. The secretion of the gland lasted for 5 days. As expected, an acute rejection reaction occurred after surgery because no immunosuppressive agents were used. Secretion from the transplanted SMG ceased within 5 days.</p><p><b>CONCLUSIONS</b>A model of SMG allotransplantation can be established in miniature swine. The technique of submandibular gland allotransplantation is feasible.</p>

Interleukin-18 and its related cytokines in plasma of patients with idiopathic thrombocytopenic purpura / 中国实验血液学杂志

To explore the role of immune regulating cytokines in pathogenesis of the idiopathic thrombocytopenic purpura (ITP) and its clinical significance, the levels of IL-18, TNF-alpha and Sc5b-9 in plasma of 32 ITP patients and 18 normal individuals were detected using ELISA methods. The results showed that IL-18, TNF-alpha and sC5b-9 levels in plasma of ITP patients were higher than that in normal individuals. The level of IL-18 was positively correlated with the levels of TNF-alpha and sC5b-9. In conclusion, The rising levels of the IL-18, TNF-alpha and sC5b-9 were correlated with disorder of Th1/Th2 subsets, and may contribute to the immune dysfunction in ITP patients. The dynamic observation of these cytokines may be useful in directing the clinical treatment for ITP patients.