Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Objective: To understand the detection rate, epidemic pattern of respiratory syncytial virus (RSV) in hospitalized children with acute lower respiratory tract infection (ALRTI) in China. Methods: From June 2017 to March 2020, a prospective multi-center study on the viral aetiology among hospitalized children with ALRTI was conducted in six pediatrics hospital of North China, Northeast, Northwest, South China, Southeast, and Southwest China. A total of 2 839 hospitalized children with ALRTI were enrolled, and the respiratory specimens were collected from these cases. A multiplex real-time RT-PCR assay were employed to screen the respiratory viruses, and the molecular epidemiological and clinical characteristics of children infected with RSV were analyzed. Results: The positve rate of RSV was 18.6% (528/2 839), and the positive rate of RSV in different regions ranged from 5.5% to 44.3%. The positive rate of RSV in male was higher than that in female (20.2% vs 16.3%), and there was a significant statistically difference between two groups (χ2=6.74, P=0.009). The positive rate of RSV among children under 5 years old was higher than that among children older than 5 years old (22.3% vs 4.5%), and there was a significant statistically difference between two groups (χ2=97.98,P<0.001). The positive rate of RSV among the <6 months age group was higher than that of other age groups (all P<0.05). During January 2018 and December 2019, RSV was detected in almost all through the year, and showed peaks in winter and spring. RSV-positive cases accounted for 17.0% (46/270) among children with severe pneumonia, including 36 cases infected with RSV alone. Conclusion: RSV is an important viral pathogen in children under 5 years old with ALRTI in China. The virus can be detected almost all through the year and reached the peak in winter and spring. RSV could lead to severe pneumonia in children and caused huge threaten to children's health.
Child ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Respiratory Syncytial Virus Infections/epidemiology* ; Child, Hospitalized ; Prospective Studies ; Respiratory Tract Infections/epidemiology* ; Respiratory Syncytial Virus, Human ; China/epidemiology*

Objective: To investigate effectiveness of different intensities of basketball exercise on body compositions among obese junior middle school students, and to provide theoretical support for healthy weight loss among obese children and adolescents. Methods: From September to November 2020,a typical sampling method was used to select 48 obese junior middle school students were recruited from Wuhan Optical Valley Experimental Middle School according to body mass index(BMI), all the students were divided into high, moderate and low intensity basketball training group, as well as the control group, the 45 min per times basketball exercise intervention was administered three times per week for 12 weeks, while the control group did not received no intervention, body composition was assessed before and after intervention. Results: After 12 weeks of low intensity basketball exercise, the percentage of body fat of obese junior high school students after intervention was significantly higher than that before intervention[(32.16±2.26)% v.s. (34.33±2.35)%] ( t =3.52, P <0.05). There was no significant difference in other indexes body weight, body mass index, waist circumference, skeletal musclebetween before and after intervention ( t =2.31, 1.98, 1.26,-1.65, P >0.05). For moderate intensity basketball exercise group obdy weight, BMI, percentage of body fat and waist circumference showed statistical changes before and after intervention( t=3.44, 3.76, 6.56, 2.45, P <0.05). For high intensity basketball exercise group, all body composition indicators showed significant changes( t=4.14, 5.18, 11.26, 5.89, -2.56, P <0.05). Conclusion Twelve weeks of basketball exercise can effectively improve body composition of obese junior middle school students, with higher the intensity of exercise, the better the effectiveness.

Objective:To evaluate the personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture.Methods:A retrospective analysis was conducted of the 30 patients who had been treated for malunion of tibial fracture at Department of Orthopaedics, The First Affiliated Hospital to Zhengzhou University from January 2010 to January 2018. Of them, 15 used a personalized 3D printed guide template in the osteotomy (3D printing group). They were 9 males and 6 females, with an age of 46.3 year±8.2 years. The fracture malunion was located in the upper and middle tibia in 11 cases, in the lower tibia in 4 cases, on the left side in 6 cases and on the right side in 9 ones. There were 8 cases of varus deformity and 7 ones of valgus deformity. Their preoperative fracture deformity angle was 24.3°±5.5°. The other 15 patients were treated with conventional surgery (conventional group). They were 10 males and 5 females, with an age of 47.1 years±6.0 years. The fracture was located in the upper and middle tibia in 12 cases, in the lower tibia in 3 cases, on the left side in 5 cases and on right side in 10 cases. There were 7 cases of varus deformity and 8 ones of valgus deformity. Their preoperative fracture deformity angle was 22.5°±5.4°. The 2 groups were compared in terms of preoperative baseline data, operation time, intraoperative blood loss and postoperative recovery of the alignment of lower limb.Results:There were no significant differences in the preoperative baseline data between the 2 groups, showing comparability ( P>0.05). The 3D printing group was followed up for an average of 12 months while the conventional group for an average of 10 months. The operation time for the 3D printing group was significantly shorter than that for the conventional group(102.2 min±13.0 min versus 137.9 min ±10.5 min), the intraoperative blood loss for the former significantly less than that for the latter (77.3 mL ± 39.7 mL versus 163.3 mL ± 35.2 mL), and the postoperative malunion angle in the former significantly smaller than that in the latter (1.9°±0.4° versus 3.2°±0.9°) (all P< 0.05). The last follow-ups revealed no implant failure or re-malunion but fine healing of the osteotomy sites and good recovery of the alignment of lower limb in the 2 groups. Conclusion:A personalized 3D printed guide template used in the osteotomy for malunion of tibial fracture is an effective aid because it can facilitate precise osteotomy, reduce operation time and intraoperative blood loss and help correct the alignment of lower limb, leading to good short-term surgical outcomes.

Objective:To explore the clinical effect of bench treadmill training on functional recovery for patients with severely burnt on lower limbs. Methods:From October, 2016 to December, 2017, 30 patients with severe lower limb burn were divided into control group (n = 15) and observation group (n = 15). The control group accepted routine comprehensive rehabilitation, while the observation group accepted the bench treadmill training in addition. They were assessed with the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Numerical Rating scale (NRS) of pain, Berg Balance Scale (BBS) and 6-minute walking test (6MWT) before and after six weeks of treatement. Results:The scores of SAS, SDS and NRS decreased in both groups (t > 3.636, P < 0.01), and they were less in the observation group than in the control group (t > 2.319, P < 0.05). The score of BBS and distance of 6MWT increased in the observation group compared with those in the control group (t > 2.541, P < 0.05). Conclusion:Early training with bench treadmill may promote the functional recovery for patients with severe lower limbs burns.

Background:Traditional tissue engineering methods to fabricate urinary tract patch have some drawbacks such as compromised cell viability and uneven cell distribution within scaffold.In this study,we combined three-dimensional (3D) bioprinting and tissue engineering method to form a tissue-engineered urinary tract patch,which could be employed for the application on Beagles urinary tract defect mode to verify its effectiveness on urinary tract reconstruction.Methods:Human adipose-derived stem cells (hADSCs) were dropped into smooth muscle differentiation medium to generate induced microtissues (ID-MTs),flow cytometry was utilized to detect the positive percentage for CD44,CD105,CD45,and CD34 of hADSCs.Expression of vascular endothelial growth factor A (VEGFA) and tumor necrosis factor-stimulated gene-6 (TSG-6) in hADSCs and MTs were identified by Western blotting.Then the ID-MTs were employed for 3D bioprinting.The bioprinted structure was encapsulated by transplantation into the subcutaneous tissue of nude mice for 1 week.After retrieval of the encapsulated structure,hematoxylin and eosin and Masson's trichrome staining were performed to demonstrate the morphology and reveal collagen and smooth muscle fibers,integral optical density (IOD) and area of interest were calculated for further semiquantitative analysis.Immunofluorescent double staining of CD31 and a-smooth muscle actin (α-SMA) were used to reveal vascularization of the encapsulated structure.Immunohistochemistry was performed to evaluate the expression of interleukin-2 (IL-2),α-SMA,and smoothelin of the MTs in the implanted structure.Afterward,the encapsulated structure was seeded with human urothelial cells.Immunofluorescent staining of cytokeradns AE1/AE3 was applied to inspect the morphology of seeded encapsulated structure.Results:The semi-quantitative assay showed that the relative protein expression of VEGFA was 0.355 ± 0.038 in the hADSCs vs.0.649 ± 0.150 in the MTs (t--3.291,P =0.030),while TSG-6 expression was 0.492 ± 0.092 in the hADSCs vs.1.256 ± 0.401 in the MTs (t =3.216,P =0.032).The semi-quantitative analysis showed that the mean IOD of IL-2 in the MT group was 7.67 ± 1.26,while 12.6 ± 4.79 in the hADSCs group,but semi-quantitative analysis showed that there was no statistical significance in the difference between the two groups (t =1.724,P =0.16).The semi-quantitative analysis showed that IOD was 71.7 ± 14.2 in noninduced MTs (NI-MTs) vs.35.7 ± 11.4 in ID-MTs for collagen fibers (t =3.428,P =0.027) and 12.8 ± 1.9 in NI-MTs vs.30.6 ± 8.9 in ID-MTs for smooth muscle fibers (t=3.369,P=0.028);furthermore,the mean IOD was 0.0613 ±0.0172 in ID-MTs vs.0.0017 ± 0.0009 in NI-MTs for α-SMA (t =5.994,P =0.027),while 0.0355 ± 0.0128 in ID-MTs vs.0.0035 ± 0.0022 in NI-MTs for smoothelin (t=4.268,P =0.013),which indicate that 3D bioprinted structure containing ID-MTs could mimic the smooth muscle layer of native urinary tract.After encapsulation of the urinary tract patch for additional cell adhesion,urothelial cells were seeded onto the encapsulated structures,and a monolayer urothelial cell was observed.Conclusion:Through 3D bioprinting and tissue engineering methods,we provided a promising way to fabricate tissue-engineered urinary tract patch for further investigation.

Objective To investigate the regulatory effect of branched chain amino acids (BCAA) on the expression of apoptosis related proteins after cerebral ischemia reperfusion injury and the protective effects of BCAA on ischemic brain injury in rats.Methods 40 male SD rats were randomly divided into normal diet group (n =20) and branched chain amino acid (BCAA) group (n=20) according to the random number table,and each group was randomly divided into control group (n=6),sham operation group (n=6) and model group (n =8) which used suture method to make ischemia reperfusion model.After modeling,modified Neurological Severity Scores (mNSS) was used to access the neurological impairment degree of 2,6,24,48 and 72 h in each group.The expression of apoptosis related proteins (Cleaved,Bax/Bcl-2) after 72 h was detected by the method of immune protein imprinting (Caspase3) and compared between normal diet group and BCAA group.Results Compared with the normal diet rats,the mNSS of BCAA diet rats after modeling at 2,6,24,48,72 h decreased (11.35±2.78 vs.7.15±2.41,P=0.019;9.35±1.75 vs.5.82±1.17,P=0.002;6.11±1.16vs.4.39±1.46,P=0.048;5.87±1.32vs.3.55±1.94,P=0.036;4.98±2.24vs.2.09±1.33,P=0.022).The expression of cleaved caspase3 protein and the ratio of Bax/Bcl-2 decreased in BCAA group.Conclusion BCAA can alleviate the apoptosis of rats after ischemia and reperfusion,reduce the damage of nerve function,and has a positive protective effect on ischemic brain injury.

This paper reviewed the present nursing manager succession planning at home and abroad, covering the succession standard of nursing managers, the content and form of pre-job training, and the evaluation tool of management ability. These efforts aim to provide references for the construction of nursing management talents teams in China.