Contrast-zero ultrasound-guided transcatheter aortic valve replacement: A case report / 中国胸心血管外科临床杂志

@#Conventional transcatheter aortic valve replacement is normally recommended with transthoracic echocardiography, and contrast agent mediated fluoroscopy under anesthesia to guide a better implantation of the transcatheter valve. However, iodine-containing contrast agent possibly damages the patient’s kidney, and even induces the acute kidney injury. We reported a 75-year-old patient diagnosed with severe aortic valve stenosis, moderate regurgitation, and chronic renal failure. We performed the aortic valve replacement under the guidance of fluoroscopy and transesophageal ultrasound without contrast agent. Seven days after surgery, the patient recovered well and discharged with alleviated aortic stenosis and fixed transcatheter aortic valve.

Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation / 中华儿科杂志

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues / 中华病理学杂志

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

Network controllability analysis of awake and asleep conditions in the brain / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The difference between sleep and wakefulness is critical for human health. Sleep takes up one third of our lives and remains one of the most mysterious conditions; it plays an important role in memory consolidation and health restoration. Distinct neural behaviors take place under awake and asleep conditions, according to neuroimaging studies. While disordered transitions between wakefulness and sleep accompany brain disease, further investigation of their specific characteristics is required. In this study, the difference is objectively quantified by means of network controllability. We propose a new pipeline using a public intracranial stereo-electroencephalography (stereo-EEG) dataset to unravel differences in the two conditions in terms of system neuroscience. Because intracranial stereo-EEG records neural oscillations covering large-scale cerebral areas, it offers the highest temporal resolution for recording neural behaviors. After EEG preprocessing, the EEG signals are band-passed into sub-slow (0.1‍-‍1 Hz), delta (1‍-‍4 Hz), theta (4‍-‍8 Hz), alpha (8‍-‍13 Hz), beta (13‍-‍30 Hz), and gamma (30‍-‍45 Hz) band oscillations. Then, dynamic functional connectivity is extracted from time-windowed EEG neural oscillations through phase-locking value (PLV) and non-overlapping sliding time windows. Next, average and modal network controllability are implemented on these time-varying brain networks. Based on this preliminary study, it appears that significant differences exist in the dorsolateral frontal-parietal network (FPN), salience network (SN), and default-mode network (DMN). The combination of network controllability and dynamic functional networks offers new insight for characterizing distinctions between awake and asleep stages in the brain. In other words, network controllability captures the underlying brain dynamics under both awake and asleep conditions.

Secondary subaortic stenosis following ventricular septal defect closure: A retrospective study in a single center / 中国胸心血管外科临床杂志

@#Objective     To summarize the characteristics of children diagnosed with secondary subaortic stenosis after the surgical closure for ventricular septal defect and explore its potential mechanism. Methods     We retrospectively collected patients aged from 0 to 18 years, who underwent ventricular septal defect closure and developed secondary subaortic stenosis, and subsequently received surgical repair from 2008 to 2019 in Fuwai Hospital. Their surgical details, morphological features of the subaortic stenosis, and the follow-up information were analyzed. Results     Six patients, including 2 females and 4 males, underwent the primary ventricular septal defect closure at the median age of 9 months (ranging from 1 month to 3 years). After the first surgery, patients were diagnosed with secondary subaortic stenosis after 2.9 years (ranging from 1 to 137 months). Among them, 2 patients underwent the second surgery immediately after diagnosis, and the other 4 patients waited 1.2 years (ranging from 6 to 45 months) for the second surgery. The most common type of the secondary subaortic stenosis after ventricular septal defect closure was discrete membrane, which located underneath the aortic valve and circles as a ring. In some patients, subaortic membrane grew along with the ventricular septal defect closure patch. During the median follow-up of 8.1 years (ranging from 7.3 to 8.9 years) after the sencond surgery, all patients recovered well without any recurrence of left ventricular outflow tract obstruction. Conclusion     Regular and persistent follow-up after ventricular septal defect closure combining with or without other cardiac malformation is the best way to diagnose left ventricular outflow tract obstruction in an early stage and stop the progression of aortic valve regurgitation.

Association of intraperitoneal pressure and clinical symptoms in peritoneal dialysis patients / 中华肾脏病杂志

Objective:To explore the association between the intraperitoneal pressure (IPP) and clinical symptoms in peritoneal dialysis (PD) patients.Methods:It was a cross-sectional study. PD patients of Peking University First Hospital from January 1, to October 31, 2021, were enrolled according to the inclusion and exclusion criterion. The gold standard—Durand method was used to measure the IPP of PD patients for 2 L intraperitoneal volume, and clinical and laboratory data were collected. According to whether the IPP ≥ 18 cmH 2O or not, the participants were divided into elevated IPP group and normal IPP group. A self-designed semi-quantitative questionnaire was used to investigate the frequency and degree of five clinical symptoms, including abdominal distension, bloating, acid reflux, hiccup and chest tightness or suffrage, as well as the degree of symptom relief after emptying peritoneal dialysate. Pearson or Spearman correlation analysis was used to analyze the correlation between each variable and intraperitoneal pressure. Results:A total of 194 PD patients were enrolled, with age of (51.6±12.9) years old. Of them, there were 123 males (63.4%), 71 females (36.6%) and 60 patients (30.9%) with diabetes. The median dialysis vintage was 24.0 (10.0, 54.0) months. The IPP was (16.2±4.3) cmH 2O, and 70 (36.1%) patients had elevated IPP. Correlation analysis results showed that IPP was positively correlated with body weight ( r=0.23, P<0.001), body mass index ( r=0.41, P<0.001), body surface area ( r=0.15, P=0.030), triglyceride ( r=0.22, P=0.001), high-sensitivity C-reactive protein ( r=0.20, P<0.001), and negatively correlated with diabetes ( r=-0.14, P=0.034) and serum calcium ( r=-0.15, P=0.034). There was no significant correlation between IPP and the total frequency score of five clinical symptoms ( r=0.122, P=0.092). The frequency of stomach distension in elevated IPP group was significantly higher than that in normal IPP group ( P=0.002), and there were no significant differences in the degree and relief degree of stomach distension between the two groups (all P>0.05). There were no statistically significant differences in the extent, frequency and degree of relief of other four clinical symptoms between the two groups (all P>0.05). Conclusion:The increased IPP has little correlation with clinical symptoms, suggesting that it may be unreliable to adjust the infusion volume only by the subjective feeling of patients. It is necessary to monitor IPP as an objective variable.

Dosimetric effects of prone immobilization devices combined with a belly-board in intensity-modulated radiotherapy for gynecologic cancers / 中华放射医学与防护杂志

Objective:To investigate the dosimetric effects of prone immobilization devices combined with a belly board (PIDBBs) in the intensity-modulated radiotherapy (IMRT) for gynecologic cancers.Methods:A total of 20 patients with cervical or endometrial cancer treated with radiotherapy in the Third Affiliated Hospital of Sun Yat-sen University from August 2020 to June 2021 were retrospectively analyzed. Two sets of body contours were outlined for each patient. One set of body contours did not contain the immobilization devices, and the other contour set included the immobilization devices. For each patient, doses were calculated for the two sets of contours using the same 7-field IMRT plan and were recorded as Plan without and Plan with. The dosimetric difference caused by the immobilization devices was assessed by comparing the parameter values in the dose-volume histograms (DVHs) and by plan subtraction. The Gafchromic EBT3 film and anthropomorphic phantom were used to verify the calculated doses. Results:The target coverage and average dose of Plan with were lower than those of Plan without. Specifically, the V50 Gy, V49 Gy, and Dmean of planning target volume (PTV) decreased by 19.75%, 7.99%, and 2.54% ( t = 8.96, 10.49, 22.09, P < 0.01), respectively. The V40 Gy, V30 Gy, V20 Gy, V15 Gy, and Dmean of skins increased by 51.79%, 51.05%, 45.72%, 33.63% and 10.80% ( t = -2.54, -5.63, -15.57, -24.06, -13.88, P < 0.01), respectively. Doses to other organs at risk (OARs) showed no significant differences. As indicated by the EBT3 measurements, the doses to skins of the abdomen and pelvis on the anthropomorphic phantom increased by approximately 37.24% ( t = 10.86, P<0.01). Conclusions:Although PIDBBs can effectively reduce the low dose to the small intestine, the radiation attenuation caused by them can reduce the PTV coverage of radiotherapy plans and increase the doses to abdominal and pelvic skins sharply, especially for patients requiring irradiation of the groin and perineum.

Caudate nucleus and thalamus in untreated patients with obsessive-compulsive disorder: a magnetic resonance spectroscopy study / 中华行为医学与脑科学杂志

Objective:To investigate the neurobiochemical metabolites of caudate nucleus and thalamus in patients with obsessive-compulsive disorder and their relationship with obsessive-compulsive symptoms.Methods:From April 2019 to January 2022 in Beijing Anding Hospital, totally 25 untreated patients with obsessive-compulsive disorder were recruited, and 20 healthy controls matched with gender, age and educational background were recruited for the study.The maps of neurobiochemical metabolites of patients and normal controls were collected by hydrogen proton magnetic resonance spectroscopy.With bilateral caudate nucleus and thalamus as brain regions of interest.The relative concentrations of N-acetylaspartic acid (NAA), glutamic acid (Glu) and γ-aminobutyric acid (GABA) were fitted by LCModel software.At the same time, the clinical symptoms of patients were evaluated with Yale-Brown obsessive-compulsive scale (Y-BOCS) and Hamilton anxiety scale (HAMA). SPSS 20.0 software was used for statistical analysis.Independent double sample t-test was used to compare the differences of different nerve biochemical metabolite concentrations between patients with obsessive-compulsive disorders and healthy controls.Pearson correlation analysis was used to explore the correlation between biochemical metabolite concentrations and clinical symptoms. Results:The Glu concentration in the left thalamus of patients with obsessive-compulsive disorder (3.97±0.41) was higher than that of the control group (3.66±0.55)( t=-2.11, P<0.05), while the NAA concentration was (4.87±0.47)lower than that of the control group (5.15±0.44)( t=2.05, P<0.05). The GABA concentrations in the right caudate nucleus (0.50±0.18) and thalamus (0.80±0.19) were lower than those in the control group ((0.63±0.23), (0.96±0.24))( t=2.08, 2.36, both P<0.05). Pearson correlation analysis showed that the Glu concentration in the left caudate nucleus of patients with obsessive-compulsive disorder was positively correlated with the total score of Y-BOCS( r=0.46, P<0.05). Spearman correlation analysis showed that Glu concentration in the right caudate nucleus was positively correlated with the total score of HAMA in patients with obsessive-compulsive disorder ( r=0.46, P<0.05). Conclusion:NAA, Glu and GABA metabolism in caudate nucleus and thalamus are abnormal in patients with obsessive-compulsive disorder, and Glu concentration is positively correlated with the severity of obsessive-compulsive and anxiety symptoms.

Construction of narrative nursing intervention program for patients with advanced lung cancer undergoing chemotherapy based on the theory of meaning in life / 中国实用护理杂志

Objective:To construct a narrative nursing intervention program for patients with advanced lung cancer undergoing chemotherapy based on the meaning in life theory, so as to alleviate the negative psychology of patients and improve the meaning in life of patients.Methods:Using a mixed research design, based on the literature study and qualitative interview, the first draft of narrative nursing intervention program for patients with advanced lung cancer undergoing chemotherapy was constructed based on the theory of meaning in life. From June to September 2021, the Delphi method was used to conduct 2 rounds experts consultations among 15 experts from 8 hospitals, and the items were revised according to the expert′s advice.Results:The experts positive coefficients of the 2 rounds consultations were 83.33% and 100.00%, the expert authority coefficient was 0.88, and the Kendall coefficients of importance were 0.183 and 0.215, and the operational Kendall coefficients were 0.234 and 0.363. Finally, a narrative nursing intervention program for lung cancer patients based on the theory of meaning in life was formed. It included four modules: narrative theme, narrative content, narrative interview outline and homework assignment/auxiliary measures. It was performed 7 times in each chemotherapy cycle.Conclusions:The construction process of narrative nursing intervention program for patients with advanced lung cancer undergoing chemotherapy based on the theory of meaning in life is rigorous, scientific and practical and can be used to guide clinical psychological nursing intervention for patients with advanced diseases and enrich the way to seek the meaning in life of patients

Prognostic differences between type Ⅰ and type Ⅱ renal papillary cell carcinoma / 现代泌尿外科杂志

【Objective】 To analyze the clinical characteristics and prognostic differences between type Ⅰ and type Ⅱ papillary renal cell carcinoma (PRCC), and identify the prognosis-related independent predictors. 【Methods】 A total of 143 PRCC patients treated during Jan.2012 and Dec.2019 were involved, including 91 type Ⅰ patients and 52 type Ⅱ patients. The prognostic factors were analyzed with univariate and multivariate Cox regression analysis. The differences in cancer-specific survival (CSS) between the two groups were analyzed with Kaplan-Meier method and log-rank test. 【Results】 The patients’ age was 53.41±13.50 years. After a mean follow-up of 63.27±26.20 months, 14 patients died, and the overall CSS was 90.2%. The prognosis of type Ⅰ patients was better than type Ⅱ patients (94.5% vs. 82.7%, P=0.020). Cox regression suggested that PRCC subtype and stage were significantly associated with prognosis. There was no difference in prognosis between type Ⅰ and type Ⅱ patients in T1/T2 subgroup (P>0.05). However, in T3/T4 subgroup, type Ⅰ patients had a significant better prognosis than type Ⅱ patients (P=0.023), while the above trends were not observed in G1/G2 and G3/G4 subgroups (P>0.05). 【Conclusion】 PRCC subtype and stage are independent prognostic predictors. The impact of PRCC subtype on prognosis is mainly manifested in the subgroup of patients with T3 or higher stage.

Efficacy of Lauromacrogol Injection for Ablation of Benign Predominantly Cystic Thyroid Nodules and Related Factors: A Prospective Study

Objective@#To prospectively evaluate the efficacy of lauromacrogol injection for ablation (LIA) of benign predominantly cystic thyroid nodules and its related factors. @*Materials and Methods@#A total of 142 benign predominantly cystic thyroid nodules (median volume, 12.5 mL; range, 0.4– 156 mL) in 137 patients (male:female sex ratio, 36:101; mean age ± standard deviation [SD], 49 ± 13 years) were treated with LIA after being confirmed as benign via cytology. The volume reduction rate (VRR) of the nodules and cosmetic score were evaluated during follow-up at 1, 3, and 6 months after treatment and every 6 months thereafter. A VRR of ≥ 50% at the 12-month follow-up was considered to indicate effective treatment. The associations between the clinical factors and nodular ultrasound features, including the initial nodule volume, proportion of solid components, vascularity grade and ineffective treatment (VRR of < 50% at the 12-month follow-up), and regrowth were analyzed. @*Results@#All patients completed follow-up for at least 12 months. The average ± SD follow-up period was 32 ± 11 months (range, 12–54 months). The effective treatment rate was 73.2% (104/142), while the regrowth rate was 12.0% (17/142) at the last follow-up. Grade 2–3 intranodular vascularity in the solid components of the nodules was the only independent factor associated with ineffective treatment, with an odds ratio (reference category, grade 0–1) of 3.054 (95% confidence interval, 1.148–8.127) (p = 0.025). @*Conclusion@#LIA is an effective treatment for predominantly cystic thyroid nodules. Grade 2–3 intranodular vascularity in the solid components of nodules is the only independent risk factor for ineffective LIA.

Analysis and identification of a case of pegaspargase-induced acute pancreatitis and literature review / 中国药房

OBJE CTIVE To investigate the clinical characteristics of a dverse drug reactions of asparaginase-associated pancreatitis（AAP），so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database ，CNKI，PubMed and Embase database，case reports of AAP were collected and summarized in terms of patient demographics ，drug use ，incubation period and adverse reaction outcome. Combined with this case ，the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification ，it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database ，and a total of 52 patients（including this patient ）were included in the analysis ，including 29 males and 23 females，mainly minors （65.4％）. L-asparaginase was the main asparaginase preparation that causes AAP （80.8％）. Gastrointestinal symptoms were the main prodromal symptoms （92.3％），which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration ，and the median latency was 14 days after administration；compared with children ，median latency of AAP in adult patients was shortened significantly （11 d vs. 16 d，P＝ 0.049）；the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase （17 d vs. 12.5 d，P＝0.490）. Of the cases included in the analysis ，8 patients died due to AAP ，1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of ； asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP ，consider the possibility ： of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.

Investigation of Intestinal Absorption Characteristics of Multi-index Components of Danggui Buxuetang Based on Drug Absorption Simulating System / 中国实验方剂学杂志

ObjectiveTo investigate the intestinal absorption characteristics of multi-index components in Danggui Buxuetang with drug absorption simulating system （DASS） established by everted intestinal sac model. MethodThe intestinal absorption solution at different time points after administration of Danggui Buxuetang was collected and detected by high performance liquid chromatography （HPLC）， acetonitrile （A）-0.2% glacial acetic acid solution （B） was used as the mobile phase for gradient elution （0-16 min， 15%-23%A； 16-20 min， 23%-28%A； 20-25 min， 28%-30%A； 25-30 min， 30%A； 30-35 min， 30%-65%A； 35-45 min， 65%-95%A）， the detection wavelength was 302 nm. HPLC fingerprint of intestinal absorption solution was established and the common peak was calibrated， and the relative cumulative absorption rate of each index component was calculated. The relative cumulative absorption curves of components were fitted with various mathematical models by DDSolver 1.0 to explore the absorption law of different components. ResultThe absorption process of C2 （calycosin-7-glucoside） and C6 in Danggui Buxuetang was in line with zero-order equation， C9 was best fitted by Weibull equation， and the remaining 7 components were in line with Makoid-Banakar equation. C1 with C2， C3， C5， C7 and C10， C2 with C5 and C7， C3 with C4， C5， C7 and C10， C4 with C6 and C10， C5 with C7， C6 with C10， C7 with C10， C8 with C9 were absorbed simultaneously during the absorption process. With the prolongation of time， the overall cumulative absorption rate of Danggui Buxuetang increased. At 120 min， the overall cumulative absorption rate of Danggui Buxuetang exceeded 38%， and reached 49.14% at 180 min. ConclusionTen ingredients in Danggui Buxuetang are absorbed in the jejunum， but absorption law of various components is different， which shows that the intestinal absorption of compound preparations of traditional Chinese medicine （TCM） has multiple characteristics. Intestinal absorption study of TCM compound preparations with chemical composition as the index can reveal some of its absorption law， but it is not complete.

The effect of narrative nursing on the meaning and quality of life in chemotherapy patients with advanced lung cancer / 中国实用护理杂志

Objective:To explore the impact of narrative nursing on the meaning and quality of life in chemotherapy patients with advanced lung cancer.Methods:A total of 86 chemotherapy patients with advanced lung cancer hospitalized in the Oncology Department of Shanghai Pulmonary Hospital Affiliated to Tongji University from October 2020 to November 2021 were selected and divided into control group with 42 cases and narrative group with 44 cases by random number table method. The control group was treated with routine nursing of patients with tumor chemotherapy while the narrative group was implemented on narrative nursing intervention as well as routine nursing. A total of 12 to 14 times, each chemotherapy period was 7 times. The effect of the intervention was assessed by Meaning in Life Scale for Advanced Cancer Patients (MiLS)、Chinese Version of the Functional Assessment of Cancer Therapy-Lung(FACT-L 4.0) and Distress Thermometer (DT) before intervention, 1 week, 3 weeks and 2 months after intervention.Results:Forty cases in the control group and 42 cases in the narrative group were involved in the statistical analysis. Two months after intervention, the total score of MiLS, the score of the will to search for meaning, the meaning of life and satisfaction,existential frustration, life control, suffering tolerance and death acceptance in the control group were (98.60 ± 9.17), (14.90 ± 1.91), (13.38 ±2.62), (16.40 ± 2.73), (26.48 ± 3.19), (14.30 ± 1.68), (13.15 ± 3.07) points, which were significantly lower than those in the narrative group (112.02 ± 9.73), (16.45 ± 2.24), (16.31 ± 1.96), (19.40 ± 2.42), (28.76 ±3.48), (16.14 ± 1.82), (14.95 ± 2.39) points, and the difference were statistically significant ( t value were -6.42 --2.98, all P<0.01), and the main effect between groups and time were statistically significant ( F values were 2.76-24.47, all P<0.05). Two months after intervention, the total score of FACT-L, social/family status, emotional status, functional status and lung cancer specific module in control group were (90.75 ± 11.65), (18.58 ± 3.75), (15.65 ± 3.85), (13.48 ± 3.34), (22.00 ± 4.93) points, which were lower than those in the narrative group (102.12 ± 9.32), (20.36 ± 4.29), (18.10 ± 3.25), (16.74 ± 4.05), (24.80 ±3.83) points, the differences were statistically significant ( t values were-4.89--1.99, all P<0.05), and there was intergroup effect ( F values were 5.14-24.47, all P<0.05). Three weeks and 2 months after intervention, the psychological distress score of control group were (3.88 ± 2.73), (3.60 ± 2.19) points, which were significantly higher than the narrative group (2.52 ± 2.18), (1.90 ± 1.78) points, and the differences were statistically significant ( t=2.50, 3.85, both P<0.05), with a time, groups, interaction effect ( F=15.29, 15.86, 2.80, all P<0.05). Conclusions:Narrative nursing can effectively improve the meaning and quality of life and relieve psychological distress in chemotherapy patients with advanced lung cancer. It is worthy of clinical promotion.

Mechanism of gamma-chain cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 in CD8+ T cells of chronic hepatitis B patients / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of gamma-chain (γC) cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) in CD8+ T cells of chronic hepatitis B (CHB) patients. MethodsA total of 23 CHB patients who attended Tangdu Hospital, Fourth Military Medical University, from January to May, 2017, were enrolled. Peripheral blood was collected from all patients, and Ficoll density gradient centrifugation was used to isolate peripheral blood mononuclear cells (PBMCs). PBMCs were stimulated with interleukin-7 (IL-7), interleukin-15 (IL-15), and interleukin-21, respectively, and then anti-γC antibody and/or anti-IL-7Rα, anti-IL-2Rβ, and anti-IL-21R were added to the culture solution. After 96 hours of culture, flow cytometry was used to measure the expression of TIM-3, interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon-γ (IFNγ) and the phosphorylation level of signal transducer and activator of transcription (STAT) in CD8+ T cells. A one-way analysis of variance and the least significant difference t-test were used for comparison of continuous data. ResultsThe CD8+ T cells stimulated by IL-7 and IL-15 had a significantly higher percentage of TIM-3-positive CD8+ T cells than those without stimulation (t=9.966 and 9074, P＜0.05), as well as significantly higher expression levels of IL-2, IL-10, and IFN-γ and phosphorylation levels of STAT-5 and STAT-1 (all P＜0.05). Stimulation with anti-IL-7Rα and anti-γC antibody significantly reduced the elevated expression levels of TIM-3, IL-2, and IL-10 in the IL-7 stimulation group (t=5.537, 6.224, and 4.500, P＜0.05). Stimulation with anti-IL-2Rβ alone or in combination with anti-γC antibody significantly reduced the expression levels of TIM-3 and IL-2 and the phosphorylation level of STAT-1 in the IL-15 stimulation group (P ＜0.05). ConclusionIL-7 and IL-15 can upregulate the expression of TIM-3 in CD8+ T cells of CHB patients, possibly via the γC receptor-mediated STAT-cytokine signaling pathway.

Integrated

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Exosomal miR-574-5p Promotes Proliferation, Invasion and Migration of Glioma Cells by Down-regulating LATS2 / 中国生物化学与分子生物学报

Exosomes are involved in invasion, migration and angiogenesis of tumor cells, and invasion is the main cause of death in glioma patients. Studies have shown that the exosomes secreted by tumor cells can carry miRNA into the receptor cells and regulate the biological functions of the receptor cells, such as proliferation, migration and invasion. miR-574-5p plays a key role in the occurrence and development of a variety of tumors. However, whether the exosomes derived from glioma cells express miR-574-5p and its role in the growth, invasion and migration of glioma cells have not been reported. This study investigated the mechanism of the exosomal miR-574-5p secreted from glioma cells in the process of cell proliferation, migration and invasion. The exosomes were characterized by electron microscopy, nanoparticle size tracking and Western blot. The results displayed that the extracted exosomes were round particles with a diameter of 30 ~ 100 nm. The internalization of exosomes was detected by immunofluorescence assay. The results showed that exosomes were internalized into LN229 cells; Bioinformatics and online data were used to screen the differentially secreted miRNA between LN229 and H4 glioma cells. The results showed that the differentially secreted miRNA was miR-574-5p, and large tumor suppressor 2 (LATS2) was predicted to be the target gene of miR-574-5p; Duel luciferase reporter assay confirmed that miR-574-5p was complementary to the 3'UTR region of LATS2; The transfection assay, qRT-PCR and Western blot was conducted to measure the relationship between miR-574-5p and LATS2. The results demonstrated that there was no significant difference in LATS2 mRNA levels between the control group and the group with miR-574-5P overexpression (P > 0.05), suggesting the regulatory effect of miR-574-5P on LATS2 was achieved by inhibiting its translation (P < 0.05). CCK-8, Transwell migration and invasion assays were conducted to explore the effect of miR-574-5p on proliferation, migration and invasion of LN229 cells. The results showed that overexpression of miR-574-5p could significantly promote the ability of proliferation, migration and invasion of LN229 cells (P < 0.05). In addition, Western blot was performed to measure the expression of kinase proteins involved in the LATS2/YAP signaling pathway, and the influence of the exosomes on this signaling pathway. The results revealed that the exosomes down-regulated the protein expression level of LATS2 and reduced p-YAP phosphorylation. In conclusion, the exosomal miR-574-5p can promote the proliferation, migration and invasion of glioma cells by down-regulating LATS2 and activating LATS2/YAP signaling pathway, which may provide a potential biomarker for the diagnosis and target for the treatment of glioma.

Effect of FLT3-ITD Length on 32D Cell Proliferation, Apoptosis and Sensitivity to FLT3 Inhibitor / 中国实验血液学杂志

OBJECTIVE@#To study the effects of FLT3-ITD length on 32D cell proliferation, apoptosis and sensitivity to FLT3 inhibitor, so as to provide references for stepwise therapy of FLT3-ITD mutated acute myeloid leukemia patients.@*METHODS@#Three different FLT3-ITD mutants with same or adjacent insert sites were selected and constructed in an eukaryotic expression vector. FLT3-ITD mutants stably expressed 32D cell strains were selected with the help of lentivirus system and IL3 free cell culture medium. The proliferation and apoptosis of 32D cell strains after AC220 treatment were detected.@*RESULTS@#FLT3-ITD mutants (ITD1, ITD2 and ITD3) stably expressed 32D cell strains were constructed successfully. In the absence of IL3 factor, the proliferation number of ITD1, ITD2 and ITD3 cell strains were mounted up to 2.3 folds, 3.7 folds, and 4.3 folds after 48 hours, respectively. Under the exposure of FLT3 inhibitor AC220, the IC@*CONCLUSION@#FLT3-ITD mutant expressed cell strains with longer ITD show higher capacity of proliferation and higher tolerance to AC220 treatment.

Amyloid and tau positive mild cognitive impairment: clinical and biomarker characteristics of dementia progression / 中华医学杂志(英文版)

BACKGROUND@#According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.@*METHODS@#We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.@*RESULTS@#pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient's study partner language domain could predict progression to dementia in A+T+MCI within 2 years.@*CONCLUSIONS@#In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

Preliminary results of five cases of laparoscopic adrenalectomy assisted by domestic robotic surgery system / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of domestic Kangduo robotic surgery system in adrenalectomy.Methods:This study summarized the clinical data of patients with adrenal adenoma who were operated by domestic kangduo robot from November 2020 to April 2021. This study was approved by the hospital ethics committee, and the clinical trials of medical devices were filed. Inclusion criteria: age 18-75 years old; all of them in accordance with the indication of adrenalectomy; tumor volume≤6 cm; agree to sign the informed consent, follow the doctor's advice and follow up regularly. Exclusion criteria: patients with ipsilateral upper abdominal surgery history; patients with severe uncontrolled disease or acute infection; patients with cardiovascular and cerebrovascular diseases, blood system diseases and immune system diseases that are not controlled and can not reach the operation standard; pregnant or lactating women. All patients underwent robot assisted adrenalectomy. The general information and perioperative data of the patients were summarized.Results:Five patients were included in this study, including 1 male and 4 female. The average age was 49 (34-61)years old. There were 2 cases on the left and 3 cases on the right. The average diameter of tumor was 2.2 (1.1-3.7) cm. All patients showed adenoma by CT examination. Two cases were diagnosed as primary aldosteronism, one as Cushing's syndrome, and two as nonfunctional adenoma. All the operations were successfully completed in 5 cases, including 4 cases via retroperitoneal approach and 1 case via peritoneal approach. The average docking time was 3.8 (3-6) min, the average operation time was 56.2 (21-92) min, and the average blood loss was 34 (20-50) ml. The postoperative pathology was adrenal cortical adenoma. The average postoperative hospital stay was 3.6 (3-5) days. No postoperative complications occurred in 5 cases. Two patients with primary aldosteronism had hypertension and hypokalemia before operation, and they needed oral antihypertensive drugs to control them. They did not need medication after operation, and their blood pressure and potassium were maintained at normal levels. All patients were followed up for average 1.5(0.5-5.0)months.Conclusions:Domestic robot assisted laparoscopic adrenalectomy has the advantages of few blood loss, short operation time, few complications. It’s a safe and effective operation, but the conclusion needs to be further verified by large sample and multi-center study.