OBJECTIVES: To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells). METHODS: CCK8 assay was used to determine the inhibition rate of oxaliplatin-treated CRC cells. A CRC/OXA cell line was constructed, in which DTX2 expression level was detected. The cells were transfected with a DTX2-shRNA plasmid or co-transfected with DTX2-shRNA and pcDNA-Notch2, and the changes in cell proliferation, migration and invasion ability were evaluated using plate cloning assay, scratch assay and Transwell invasion assay. The expression levels of Notch2, NICD and epithelial-mesenchymal transition (EMT) proteins of the transfected cells were detected with Western blotting. In a nude mouse model bearing SW620/OXA cell xenografts, the effects of DTX2 knockdown and Notch2 overexpression in the implanted cells on tumor growth and protein expressions were tested. RESULTS: The IC₅₀ of oxaliplatin was 6.00 μmol/L in SW620 cells and 8.00 μmol/L in LoVo cells. CRC/OXA cells showed a significantly increased expression of DTX2. DTX2 knockdown in CRC/OXA cells significantly inhibited cell proliferation, migration and invasion, and these effects were reversed by co-transfection of the cells with pcDNA-Notch2. DTX2 knockdown significantly reduced the expression levels of Notch2, NICD and vimentin proteins and increased E-cadherin expression in CRC/OXA cells, and co-transfection with pcDNA-Notch2 potently attenuated the changes in these proteins. In the tumor-bearing mice, DTX2 overexpression obviously promoted the growth of SW620/OXA cell xenograft, enhanced the protein expressions of Notch2, NICD and vimentin, and lowered the expression of E-cadherin. CONCLUSIONS High expression of DTX2 promotes proliferation, migration, invasion and EMT of CRC/OXA cells through the Notch2 signaling pathway, suggesting the potential of DTX2 as a target to improve the efficacy of oxaliplatin.
Epithelial-Mesenchymal Transition ; Humans ; Cell Proliferation ; Oxaliplatin ; Colorectal Neoplasms/metabolism* ; Animals ; Drug Resistance, Neoplasm ; Receptor, Notch2/metabolism* ; Cell Line, Tumor ; Mice, Nude ; Cell Movement ; Organoplatinum Compounds/pharmacology* ; Neoplasm Invasiveness ; Mice

Alzheimer's disease is a serious neurodegenerative disease without effective treatment. In recent years, researchers have tried to treat Alzheimer's disease with low-dose radiation therapy (LDRT) and have made some progress in animal models and clinical trials. Current studies have shown that LDRT can improve cognitive function in Alzheimer's patients by reducing β amyloid plaque deposition and reducing inflammation levels in central nervous system. In this review, we present the current preclinical and clinical studies, propose the possible mechanisms of LDRT in Alzheimer's disease, and discuss challenges in the planning of future trials.

Objective:To investigate the efficacy of functional endoscopic sinus surgery（FESS） in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps （CRSwNP） , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNP（ECRS）and 23 patients with non-eosinophilic CRSwNP（nECRS）. VAS-olfactory dysfunction （VAS-OD） score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[F（1, 43） =357.429, P<0.001; F（1, 43） =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[F（1, 43） =126.302, P<0.001; F（1, 43） =311.301, P<0.001; F（1, 43） =131.401, P<0.001; F（1, 43） =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[F（1, 43） =4.825, P=0.033; F（1, 43） =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[F（1, 43） =6.719, P=0.013; F（1, 43） =4.890, P=0.032; F（1, 43） =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratio（ELR） and SNOT-22 olfactory score and how much it changes（r=0.455, P=0.002; r=-0.414, P=0.005）, a negative correlation between T, TDI score and how much they change respectively（r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035）. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[F（1, 14） =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.
Humans ; Prospective Studies ; Nasal Polyps/surgery* ; Rhinitis/surgery* ; Sinusitis/surgery* ; Olfaction Disorders/etiology* ; Chronic Disease ; Endoscopy/adverse effects*

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT).Methods:752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results:Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 ( P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg ( P<0.001), 0.145, and 0.021 ( P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 ( P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion:The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

Objective:By using balloon occlusive hepatic angiography in cirrhotic portal hypertension to evaluate contrast doses on the detection rate of intrahepatic venous-lateral branch shunt (HVVC), and the effect on hepatic venous pressure gradient (HVPG) and portal vein pressure gradient (PPG).Methods:From Jan 2018 to Jun 2021, 131 patients received transjugular intrahepatic portosystemic shunt (TIPS) at Beijing Shijitan Hospital.Results:A positive correlation between PVP and weged hepatic venous pressure (WHVP) ( r=0.241, P=0.001) was found when only by right hepatic vein approach. Ten ml of iodine contrast medium when compared to 5ml doses found more cases of intrahepatic venous-venous lateral branch shunt. The mean PPG of patients with HVVC was significantly higher than the mean of HVPG( P<0.05).The right hepatic vein was the only reliable vein by which WHVP was measured. Conclusions:Right hepatic vein manometry,adequate ballon occlusion and using 10ml of iodine contrast help get reliable WHVP and found HVVC; HVVC can affect the consistency of HVPG and PPG.

Objective:To investigate the effects of theta burst stimulation(TBS)mode repeated transcranial magnetic stimulation (r-TMS) in the left prefrontal on negative symptoms and cognitive function in the elderly chronic schizophrenic patients.Methods:Totally 48 patients with stable chronic senile schizophrenia (24 cases in r-TMS treatment group and 24 cases in r-TMS pseudo stimulation control group) were selected. The treatment group was given the TBS mode r-TMS performed in the left dorsolateral prefrontal cortex. The control group was given pseudo stimulation at the same site. Before and after treatment, the brief psychiatric rating scale(BPRS), scale for assessment of negative symptoms(SANS), and positive and negative syndrome scale(PANSS)were used to assess mental symptoms, while Mattis-dementia rating scale(MDRS-2)and social adaptation functioning evaluation(SAFE)were used to assess cognitive function and social function. SPSS 20.0 was used for statistical analysis.Comparisons of the differences between inter groups and intra groups were conducted by independent sample t test and paired t-test. Results:(1)There were significant differences in the total score of PANSS scale((60.17±3.73), (56.67±3.12)), the negative symptom subscale score of PANSS((20.88±2.94), (17.96±2.33)) and the score of SANS((30.67±1.66), (30.25±1.45)) before and after treatment in the treatment group (all P<0.05). The D-value before and after treatment in the scores of BPRS ( t=3.513, P=0.001), PANSS ( t=6.048, P<0.01), negative symptom subscale ( t=6.610, P<0.01) and SANS ( t=8.239, P<0.01) were significantly different between the two groups. (2)There were significant differences in the scores of MDRS-2 and its sub scales before and after treatment in the treatment group (all P<0.05). The D-value before and after treatment in the scores of MDRS-2 ( t=6.216, P<0.01), attention ( t=4.596, P<0.01), start/maintain ( t=6.424, P<0.01), concept formation ( t=3.974, P<0.01), construction( t=2.194, P=0.033) and memory ( t=3.162, P=0.003) were significantly different between the two groups.(3)There was no significant difference in the SAFE score between the treatment group and the control group before and after treatment ( t=0.138, 0.142, both P>0.05). Conclusion:TBS can improve the negative symptoms and cognitive function in patients with the elderly chronic schizophrenic, but the effect of social function is not clear.

Objective:To study the efficacy of direct intrahepatic portosystemic shunt (DIPS) in treatment of Budd-Chiari syndrome (BCS).Methods:From January 1, 2015 to June 31, 2017, consecutive patients with BCS who were treated with DIPS at the Department of Interventional Therapy of Beijing Shijitan Hospital, the Liver Disease Research Center of Beijing Friendship Hospital and the General Surgery Department of Beijing Ditan Hospital were retrospectively analyzed. The symptoms, physical signs (including abdominal distension, ascites, pleural effusion, splenomegaly, hepatic encephalopathy) and perioperative laboratory results of these patients were collected and analyzed. Biochemical indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), and portal pressure gradient were compared before and 2 weeks after treatment. The patients were followed up for at least 3 years to assess their clinical symptoms, patency of shunt, oncological status and survival.Results:Of 67 patients with BCS who were included in the study, there were 45 males and 22 females, aged (38.12±23.22) years. The BCS classification of these patients were hepatic vein type ( n=65), including 62 patients with complete hepatic vein obstruction, 3 patients with hepatic vein occlusion due to thrombosis, and 2 patients with mixed hepatic vein and inferior vena cava occlusion. All 67 patients underwent DIPS with 93 stents being implanted. In addition, 43 patients underwent gastric coronary vein embolization, and 2 patients with mixed type of BCS underwent inferior vena cava stenting. The portal pressure gradient decreased from (22.17±9.16) mmHg (1 mmHg=0.133 kPa) to (9.87±4.75) mmHg, the difference was statistically significant ( P<0.05). Abdominal distension was relieved, at one month and ascites completely subsided in 3 months after operation. The liver congestion and swelling were obviously relieved. Comparison of patients 2 weeks after operation and before operation, ALT decreased from (65.28±27.75) U/L to (28.43±13.46)U/L, AST from (68.75±29.23) U/L to (26.92±13.33)U/L, TBil from (175.31±80.48)μmol/L to (45.08±26.54)μmol/L, DBil from (127.55±44.65)μmol/L to (35.12±10.77)μmol/L, and albumin increased from (31.56±7.22) g/L to (44.18±11.36)g/L, the difference was statistically significant (all P<0.05). All patients were followed up for at least 3 years. Shunt stenosis was detected in 5 patients (7.46%) with shunt expansion being performed, variceal bleeding in 2 patients (2.99%), ascites recurrence in 4 patients (5.97%) and hepatic encephalopathy in 2 patients (2.99%). No patients were diagnosed with hepatic cancer, and no patients died. Conclusion:DIPS was efficacious, safe and reliable to that BCS patients. It rapidly reduced portal venous pressure, relieved liver congestion, and restored liver morphology and liver function in these patients.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.