An interpretable knee replacement risk assessment system for osteoarthritis patients.

Objective: Knee osteoarthritis (OA) is a complex disease with heterogeneous representations. Although it is modifiable to prevention and early treatment, there still lacks a reliable and accurate prognostic tool. Hence, we aim to develop a quantitative and self-administrable knee replacement (KR) risk stratification system for knee osteoarthritis (KOA) patients with clinical features. Method: A total of 14 baseline features were extracted from 9592 cases in the Osteoarthritis Initiative (OAI) cohort. A survival model was constructed using the Random Survival Forests algorithm. The prediction performance was evaluated with the concordance index (C-index) and average receiver operating characteristic curve (AUC). A three-class KR risk stratification system was built to differentiate three distinct KR-free survival groups. Thereafter, Shapley Additive Explanations (SHAP) was introduced for model explanation. Results: KR incidence was accurately predicted by the model with a C-index of 0.770 (±0.0215) and an average AUC of 0.807 (±0.0181) with 14 clinical features. Three distinct survival groups were observed from the ten-point KR risk stratification system with a four-year KR rate of 0.79%, 5.78%, and 16.2% from the low, medium, and high-risk groups respectively. KR is mainly caused by pain medication use, age, surgery history, diabetes, and a high body mass index, as revealed by SHAP. Conclusion: A self-administrable and interpretable KR survival model was developed, underscoring a KR risk scoring system to stratify KOA patients. It will encourage regular self-assessments within the community and facilitate personalised healthcare for both primary and secondary prevention of KOA.

Development and validation of a nomogram and risk stratification system to predict overall survival after surgical repair for pediatric patients with medulloblastoma based on easily accessible variables.

OBJECTIVE: This study aimed to develop and validate a nomogram and risk stratification system for the overall survival of pediatric patients with medulloblastoma after surgical repair. PATIENTS AND METHODS: In this multicenter, retrospective study, consecutive patients who underwent surgery for medulloblastoma at Shanghai Children's Medical Center and the First Affiliated Hospital of Fujian Medical University from 2010 to 2022 formed the training and external validation datasets, respectively. Univariable and multivariable Cox regression analyses were performed to identify variables associated with mortality in the training dataset. A nomogram prediction model was developed based on independent variables in the multivariable Cox regression analysis to predict the 1-, 3-, and 5-year overall survival. The area under receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the nomogram. A risk stratification system based on the median risk score was also established to divide patients into two risk groups. RESULTS: In the training dataset, Cox regression analyses identified tumor size, brainstem involvement and chemotherapy as independent predictors for overall survival. The AUC of the nomogram was 0.75 at 1 year, 0. 75 at 3 years, 0.77 at 5 years in the training dataset, 0.74 at 1 year, 0.70 at 3 years, and 0.70 at 5 years in the validation dataset. The calibration curve for the probability of 1-, 3-, and 5-year survival showed good agreement between the nomogram prediction and actual observation in the training and validation datasets. The risk stratification system could perfectly classify patients into two risk groups, and the overall survival in the two groups had a good division. CONCLUSIONS: This low-cost, convenient, and noninvasive nomogram can be translated into clinical practice as a tool for risk stratification and individualized prognosis prediction for children with medulloblastoma.

[Relationship between blood glucose variation, collateral circulation and Batman score and prognosis after mechanical thrombectomy with Solitaire stent in acute posterior vascular occlusive stroke].

Objective: To explore the relationship between blood glucose variability, collateral circulation and basilar artery computed scan angiography score (Batman) and prognosis of mechanical thrombectomy with Solitaire stent in patients with large vascular occlusive APCI. Methods: A retrospective study was conducted on 113 patients with large vessel occlusive APCI who underwent Solitaire stent mechanical thrombectomy in the Department of Neurology of Nanyang Central Hospital from March 2021 to July 2022. According to the prognosis, they were divided into outcome group (46 cases) and adverse group (67 cases). Evaluate the prognosis based on the Modified Rankin Scale three months after the surgery. The differences in collateral circulation, GV and Batman score between the two groups were compared, and the related factors affecting the prognosis of large vessel occlusive APCI patients treated with Solitaire stent mechanical thrombectomy were analyzed by multivariate logistic regression model. Results: The age of 113 patients with acute large vessel occlusive APCI was (65.3±8.9) years old. The proportion of female was 34.5% (39 cases). Compared with the outcome group, the adverse group had a lower proportion of collateral circulation [40 cases (87.0%) vs 47 cases (70.2%)], higher GV score [(25.19±3.54) vs (30.36±4.11) points], lower Batman score [(7.49±1.52) vs (6.65±1.33) points], higher proportion of atrial fibrillation history [16 cases (23.9%) vs 4 cases (8.7%)], higher National Institutes of Health Stroke Scale (NIHSS) score at admission [(8.33±0.74) vs (7.25±0.92) points], larger core infarct volume [(32.57±4.87) vs (29.54±5.14) ml], and longer time from admission to vascular recanalization [(123.52±31.17) vs (102.47±29.54) min] (all P<0.05). Atrial fibrillation history, core infarct volume, NIHSS score at admission, time from admission to vascular recanalization, glycemic variability, collateral circulation, and Batman score were related factors for the prognosis of large vessel occlusive APCI patients treated with Solitaire stent mechanical thrombectomy, with ORvalues (95%CI) of 1.383 (1.124-1.641), 1.166 (1.007-1.350), 4.777 (1.856-12.297), 3.068 (2.379-3.757), 1.477 (1.209-1.806), 0.742 (0.654-0.831), and 0.717 (0.214-1.221), respectively (all P<0.05). Conclusion: Blood glucose variation is a risk factor for prognosis of mechanical thrombectomy with Solitaire stent in patients with large vascular occlusive APCI, and collateral circulation and Batman score are protective factors.

[Study on primary screening technique for children with autism spectrum disorder].

To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi'an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi 'an Children's Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.

[Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant].

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

[Clinical features of children with Cunninghamella spp. infection: a case report and literature review].

We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response. We searched Pubmed, Embase, CNKI, and Wanfang database for reports of cases of Cunninghamella spp. infection in children and retrieved 22 reported cases (including 12 males) with a median age of 13.5 (3-18) years. In these 22 cases, hematological malignancy was the most common underlying condition (19/22), and most of patients experienced an acute onset and rapid progression with respiratory symptoms (14/20) and fever (16/20) as the most common symptoms. CT imaging often showed unilateral lesions with varying imaging findings, including pulmonary nodules or masses, infiltrative changes, and pleural effusion. Definite diagnoses were established in 18 of the cases, and 4 had probable diagnoses; the lungs and skin were the most frequent organs compromised by the infection. A definite diagnosis of Cunninghamella spp. infection still relied on histopathological examination and fungal culture, but the molecular techniques including PCR and mNGS had shown potentials in the diagnosis. Almost all the cases received antifungal treatment after diagnosis (21/22), and 13 patients also underwent surgeries. Death occurred in 9 (42%) of the cases at a median of 19 (4-54) days after onset of the signs or symptoms. The patients receiving antifungal therapy combined with surgery had a high survival rate (9/13, 69%) than those with antifungal therapy alone (3/8, 37%). Invasive fungal disease is a common complication in immunoco-mpromised patients, but Cunninghamella spp. infection is rare and has a high mortality rate. In cases highly suspected of this disease, active diagnosis and early treatment are critical to improve the survival outcomes of the patients.

Association between Accelerometer-Measured Light-Intensity Physical Activity and Cognitive Function in Older Adults.

OBJECTIVES: This study aimed to investigate whether accelerometer-measured light physical activity (LPA) is associated with cognitive function and whether engaging in ≥3 h/day of LPA can reduce the chance of cognitive impairment among a sample of older adults in Taiwan. DESIGN: Cross-sectional study. SETTING: An outpatient department in a medical center. PARTICIPANTS: Participants were community-dwelling older adults aged 65 years and older who were able to walk independently from September 2020 to March 2021. MEASUREMENTS: A tri-axial accelerometer was used to measure LPA for 7 consecutive days, and the Mini-Mental State Examination (MMSE) scale was used to assess the chance of cognitive impairment. Multiple linear regression model and binary logistic regression model were performed to examine the association between LPA and MMSE scores. RESULTS: 145 older Taiwanese adults (51.7% men; 81.2±6.8 years; 6.9% at chance of cognitive impairment) were included. After adjusting for moderate-to-vigorous physical activity (MVPA) and wear time, we found that there was a significant association between LPA and cognitive function (95% confidence interval [CI]: 0.64-1.65; P<0.001), and further found that those who engaged in LPA ≥3 h/day were at reduced chance of cognitive impairment compared with people who engaged in LPA <3 h/day (odds ratio [OR]: 0.16; 95% CI: 0.03-0.80; P=0.025). CONCLUSION: This study demonstrated that engaging in LPA ≥3 h/day could be viewed as a protective factor for maintaining cognitive function in older adults. We recommend further longitudinal research to elucidate the association between intensity-specific LPA and cognitive function.

Effect of anhydrous betaine and hydrochloride betaine on growth performance, meat quality, postmortem glycolysis, and antioxidant capacity of broilers.

This study was conducted to investigate the effect of anhydrous betaine and hydrochloride betaine on growth performance, meat quality, relaxometry, postmortem glycolysis, and antioxidant capacity of partridge shank broiler chickens. A total of 400 one-day-old male broilers were randomly divided into 5 treatments and fed basal diets supplemented with 0 (control), 500 (L-AB) or 1,000 (H-AB) mg/kg anhydrous betaine, and 642.23 (L-HB) or 1,284.46 (H-HB) mg/kg hydrochloride betaine, respectively. Compared with the control group, anhydrous betaine supplementation significantly increased (P < 0.05) average daily gain and decreased (P < 0.05) drip loss24h in breast and thigh muscles of broilers. The H-AB group further increased (P < 0.05) breast muscle yield, pH24h, immobile water proportion (P21), the contents of crude protein and glutathione (GSH), the activities of creatine kinase (CK) and glutathione peroxidase (GPX), the mRNA expressions of glucose transporter 4 (GLUT4), protein kinase AMP-activated non-catalytic subunit gamma 3 (PRKAG3), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in breast muscle, and a*45min, GLUT4 mRNA expression in thigh muscle, and decreased (P < 0.05) drip loss48h, free water proportion (P22), the contents of lactate and malondialdehyde (MDA) in breast muscle. Moreover, the H-HB group significantly increased (P < 0.05) pH24h, P21 proportion, the activities of CK, total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and GPX, the content of GSH, the mRNA levels of Nrf2, HO-1, GPX, and γ-glutamate-cysteine ligase catalytic subunit (γ-GCLc) in breast muscle, and the activity and mRNA expression of GPX in thigh muscle, and decreased (P < 0.05) drip loss24h, P22 proportion in breast muscle, and MDA content in breast and thigh muscles. In conclusion, anhydrous betaine showed better effects than hydrochloride betaine in improving growth performance and breast muscle yield of broilers. Moreover, anhydrous betaine (1,000 mg/kg) or equimolar hydrochloride betaine supplementation could improve meat quality by decreasing drip loss, free water proportion, and lactate content, and enhancing muscle antioxidant capacity.

[Resection and free flap repair of recurrent maxillofacial and paranasal sinus skull base malignant tumor: report of 9 cases].

Objective: To investigate the treatment method and effect of surgical resection and free flap repair of recurrent malignant tumors of maxillofacial paranasal sinus and skull base. Methods: The clinical data of 9 patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors who underwent surgical resection and free flap repair in the Department of Otorhinolaryngology Head and Neck Surgery of Shandong Provincial Hospital from August 2009 to May 2019 were analyzed retrospectively, including 5 males and 4 females, aged 32-69 years. There were 4 cases of squamous cell carcinoma, 3 cases of adenoid cystic carcinoma, 1 case of myoepithelial carcinoma and 1 case of malignant fibrous histiocytoma. All patients were repaired with anterolateral femoral flap. The treatment process and postoperative effect were analyzed by descriptive statistics. Results: All patients were followed up from 16 months to 6 years. There were 6 cases of recurrence after operation, including 1 case of local recurrence and 5 cases of skull base and craniocerebral recurrence. The median tumor free survival time of recurrent patients was 35 months. Conclusion: Surgical resection and free flap repair can effectively prolong the life of patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors.

A user-friendly objective prediction model in predicting colorectal cancer based on 234 044 Asian adults in a prospective cohort.

BACKGROUND: Prediction models of colorectal cancer (CRC) had limited application for not being user-friendly. Whether fecal immunochemical tests (FITs) can help predict CRC has been overlooked. PATIENTS AND METHODS: With 1972 CRCs identified, 234 044 adults aged ≥40 years were successively enrolled between 1994 and 2008. Prediction models were developed by questionnaire/medical screening and quantitative FIT. NNS (number needed to scope to find one cancer) is time dependent, spanning entire study period. Significant 'risk factors' were family history, body mass index, smoking, drinking, inactivity, hypertension, diabetes, carcinoembryonic antigen, and C-reactive protein. RESULTS: Positive FIT (≥20 µg/g hemoglobin/feces) had cancer risk 10-fold larger than negative FIT, and within each age group, another 10-fold difference. The C statistic of FIT (0.81) with age and sex alone was superior to the 'common risk-factors' model (0.73). NNS, stratified by age and by FIT values, demonstrated a scorecard of cancer risks, like 1/15 or 1/25, in 5 years. When FIT was negative, cancer risk was small (1/750-1/3000 annually). The larger the FIT, the sooner the appearance of CRC. For every 80-µg/g increase of FIT, there were 1.5-year earlier development of CRC incidence and 1-year earlier development of CRC mortality, respectively. Given the same FIT value, CRC events appeared in the proximal colon sooner than the distal colon. CONCLUSIONS: A simple user-friendly model based on a single FIT value to predict CRC risk was developed. When positive, NNS offered a simple quantitative value, with a better precision than most risk factors, even combined. When FIT is negative, risk is very small, but requiring a repeat every other year to rule out false negative. FIT values correlated well with CRC prognosis, with worst for proximal CRC.

[Effects of different doses of glucocorticoids on minimally invasive procedures in pain patients with type 2 diabetes].

Objective: To investigate the effects of different doses of glucocorticoids on minimally invasive procedures in patients with type 2 diabetes mellitus (T2DM), and optimize the clinical pathways of minimally invasive procedures. Methods: The clinical data of 284 patients with T2DM who received minially invasive procedures from the Department of Pain Medicine, West China Hospital, Sichuan University from May 2017 to May 2020 were retrospectively reviewed. The patients were divided into two groups according to the main diagnostic types: spine-related group (n=148) and herpes zoster group (n=136). According to the cumulative dose of glucocorticoids (GCs) per unit body surface area during the hospitalization, patients were further divided into three subgroups: low-dose group (GCs<3.5 mg/m2), medium-dose group (3.5 mg/m2 ≤GCs<7 mg/m2), and high-dose group (GCs≥7 mg/m2). The clinical characteristics of the patients in different subgroups of the two diseases groups were compared. The effects of the glucocorticoids on the pain intensity, blood glucose, length of hospital stay (LOS) and total hospitalization cost were compared among the 3 subgroups of the two diseases groups. Results: There were no significant differences in the age, gender, height, weight, visual analog scale (VAS) and fasting blood glucose before procedures between the two groups (all P>0.05). The VAS score of the low-dose group from the spine-related group was 4.5±1.6, which was higher than that of the medium-dose group (3.5±1.3) (P=0.004). VAS score was 4.3±1.3 in the medium-dose group and 4.4±1.6 in the high-dose group from the herpes zoster group, which were higher than that in the low-dose group (3.5±0.9) (P=0.006). In terms of blood glucose, the impact on the fasting blood glucose before and after the procedures in the low-dose group from the spine-related group was less than that in the medium dose group (P=0.013). In the herpes zoster group, the blood glucose of the low-dose group was (11±5) mmol/L, which had less influence on the blood glucose fluctuation during the hospitalization than that in the high-dose group [(15±5) mmol/L] (P<0.05). The LOS and hospitalization cost in the low-dose group from the spine-related group were (9±4) d and (10 583±4 851) yuan, respectively, which were less than those in the medium-dose group [(11±3) d and (15 202±7 418) yuan] and high-dose group [(13±6) d and (18 100±4 138) yuan] (all P<0.05); however, there was no significant difference among different subgroups in the herpes zoster group (all P>0.05). Conclusion: When used in the patients with T2DM undergoing minimally invasive procedures for spine-related diseases, low-dose glucocorticoids can obtain more clinical benefit than high dose, and high dose can lead to raised blood glucose, prolong the LOS, and increase the hospitalization cost.

Age-related changes in liver metabolism and antioxidant capacity of laying hens.

This study aimed to investigate the age-related changes of hepatic metabolism and antioxidant capacity of laying hens at 3 different ages. A total of 192 Hy-line Brown laying hens were assigned into 3 groups: 1) 195-day-old (D195 group); 2) 340-day-old (D340 group); 3) 525-day-old (D525 group). Each group replicated 8 times with 8 hens at the same age. Higher activity of aspartate aminotransferase and lower contents of total protein and globulin were observed in the serum of 525-day-old hens in comparison with their 195-day-old counterparts (P < 0.05). The 525-day-old hens accumulated higher contents of total cholesterol and triglyceride in the liver than 195-day-old birds. Additionally, compared with hens from D195 or D340 group, 525-day-old birds exhibited a lower circulating estradiol level (P < 0.05). For antioxidant capacity, birds in the D525 group showed a higher malondialdehyde concentration in both serum and liver as compared with D195 or D340 group (P < 0.05). The 525-day-old hens also exhibited lower glutathione peroxidase activities in both serum and liver when compared with 195-day-old birds (P < 0.05). Simultaneously, there was a decline of hepatic superoxide dismutase activity in the D525 group in comparison with D195 group (P < 0.05). Compared with 195-day-old counterparts, 340-day-old birds upregulated the mRNA abundance of nuclear factor erythroid-2 related factor 2 and glutathione peroxidase 1 in the liver (P < 0.05). In contrast, hens from D525 group showed the downregulation of hepatic nuclear factor erythroid-2 related factor 2, NAD(P)H quinone dehydrogenase 1, and superoxide dismutase 1 when compared with D340 group (P < 0.05). These results indicated that increasing age can adversely affect liver metabolism and function of laying hens.

Utility of radiomic zones for risk classification and clinical outcome predictions using supervised machine learning during simultaneous 11 C-choline PET/MRI acquisition in prostate cancer patients.

PURPOSE: In most radiomic studies related to cancer research, the traditional tumor-centric view has predominated. In this retrospective study, we go beyond the single-tumor region and investigate the utility of proposed radiomic zones for risk classification and clinical outcome predictions using radiomic features extracted from 11 C-choline positron emission tomography (PET) imaging and supervised machine learning in prostate tumors. MATERIALS AND METHODS: Seventy-seven prostate tumors were selected and delineated. The prostate organ was divided into three radiomic zones, with zone-1 being the metabolic tumor zone, zone-2 the proximal peripheral tumor zone, and zone-3 the extended peripheral tumor zone. LIFEx was used for PET-radiomic feature extraction. Risk groups were created using Gleason scores (GS), prostate-specific antigen (PSA) levels, clinical TNM staging, and progression-free survival (PFS). Random forest (RF) and AdaBoost advanced machine learning algorithms were used for supervised machine learning. Accuracy, positive predictive value, area under the receiver operating characteristic curve (AreaROC), and other metrics were calculated for comparisons of predictive performance between zones. RESULTS: For the GS risk classification group, the accuracies of risk classification predictions were 71%, 71%, and 67% using RF and 65%, 64%, and 63% using AdaBoost for zones -1, -2, and -3, respectively. For the PSA group, the accuracies of risk classification predictions were 74%, 65%, and 64% using RF and 76%, 66%, and 67% using AdaBoost for zones -1, -2, and -3, respectively. For the TNM group, the accuracies of risk classification predictions were 68%, 76%, and 78% using RF and 66%, 75%, and 80% using AdaBoost for zones -1, -2, and -3, respectively. For the PFS group, the accuracies of clinical outcome predictions were 77%, 75%, and 83% using RF and 77%, 74%, and 83% using AdaBoost in zones -1, -2, and -3, respectively. CONCLUSIONS: We proposed three radiomic zones with different standard uptake value characteristics and created four risk groups of prostate cancer patients for testing this idea. We showed that these radiomic zones have different predicting strengths in classifying risk groups and might allow us to identify a radiomic zone with higher accuracy for patient outcome prediction.

The root cause analysis on failed patient-specific measurements of pencil beam scanning protons using a 2D detection array with finite size ionization chambers.

The aim of this report is to present the root cause analysis on failed patient-specific quality assurance (QA) measurements of pencil beam scanning (PBS) protons; referred to as PBS-QA measurement. A criterion to fail a PBS-QA measurement is having a <95% passing rate in a 3.0%-3.0 mm gamma index analysis. Clinically, we use a two-dimensional (2D) gamma index analysis to obtain the passing rate. The IBA MatriXX PT 2D detection array with finite size ionization chamber was utilized. A total of 2488 measurements performed in our PBS beamline were cataloged. The percentage of measurements for the sites of head/neck, breast, prostate, and other are 53.3%, 22.7%, 10.5%, and 13.5%, respectively. The measurements with a passing rate of 100 to >94%, 94 to >88%, and <88% were 93.6%, 5.6%, and 0.8%, respectively. The percentage of failed measurements with a <95% passing rate was 10.9%. After removed the user errors of either re-measurement or re-analysis, 8.1% became acceptable. We observed a feature of >3% per mm dose gradient with respect to depth on the failed measurements. We utilized a 2D/three-dimensional (3D) gamma index analysis toolkit to investigate the effect of depth dose gradient. By utilizing this 3D toolkit, 43.1% of the failed measurements were improved. A feature among measurements that remained sub-optimal after re-analysis was a sharp >3% per mm lateral dose gradient that may not be well handled using the detector size of 5.0 mm in-diameter. An analysis of the sampling of finite size detectors using one-dimensional (1D) error function showed a large dose deviation at locations of low-dose areas between two high-dose plateaus. User error, large depth dose gradient, and the effect of detector size are identified as root causes. With the mitigation of the root causes, the goals of patient-specific QA, specifically detecting actual deviation of beam delivery or identifying limitations of the dose calculation algorithm of the treatment planning system, can be directly related to failure of the PBS-QA measurements.

[Hepatitis B virus antigen peptide presentation by Epstein-Barr virus-transformed peripheral blood B cells].

Objective: To establish an Epstein-Barr virus-transformed peripheral blood B cell line (BCL), and explore its phenotypic characteristics, the ability to secrete antibodies and cytokines, and the ability to present hepatitis B virus (HBV) antigen peptide. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HBV infection. Epstein-Barr virus supernatant was incubated to construct BCL. The expression of CD19, CD138, CD38, CD27 and the production levels of IFN - γ, IL-10, IL-6 were detected by flow cytometry. BCL loaded with HBV antigen peptide was incubated with in vitro-expanded autologous T cells. Intracellular staining was used to detect the level of interferon-gamma produced by T cells. Results: Compared with untransformed peripheral blood B cells, BCL had high expression levels of CD138, CD38 and CD27, and the difference was statistically significant (P < 0.05), while the level of IL-6 production was decreased, and the difference was statistically significant (P < 0.01). BCL loaded with HBV antigen peptide had significantly enhanced the production of interferon-gamma by in vitro-expanded autologous T cells, and the difference was statistically significant (P < 0.01). Conclusion: BCL highly expresses CD138, CD38 and CD27, but its ability to produce IL-6 decreases. BCL can improve the immune response efficiency of HBV-specific T cells to HBV antigen peptide, and serve as a new tool for hepatitis B immune research.

[Effects of vestibular spontaneous nystagmus on visual smooth pursuit function].

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(ttotal=13.338, tlight=6.184, tmedium=8.436, tstrong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.

[Cytotoxic effect of photodynamic liposome gel combined with trastuzumab on drugresistant breast cancer cells in vitro].

OBJECTIVE: To evaluate the cytotoxic effect of photodynamic therapy (PDT) combined with targeted therapy using cross-linked liposomes and gels (Ce6-PC-Tmab@A-Gel) loaded with photosensitizer Chlorin (Ce6) and the tumor-targeting drug Trastuzumab (Tmab) in drug-resistant HER2+ breast cancer cells. OBJECTIVE: Ce6-PC-Tmab liposomes were prepared using the thin-film hydration method. The general properties, encapsulation efficiency and near-infrared responsivity of the nanoparticles were evaluated. Ce6-PC-Tmab@A-Gel with a shear response was prepared by freeze drying and stirring crosslinking, and its microstructure was observed with scanning electron microscopy (SEM) and the shear response evaluated using a rheometer. The inhibitory effect of Ce6-PC-Tmab@A-Gel in drug-resistant HER2+ breast cancer SK-BR-3 cells was assessed with cytotoxicity assay (MTT assay) combined with near-infrared light. OBJECTIVE: The particle size of Ce6-PC-Tmab was 239.7±9.7 nm and the potential was -2.03±0.09 mV. The entrapment efficiency of Tmab by Ce6-PC-Tmab liposomes was (40.22± 0.73)%. The prepared Ce6-PC-Tmab@A-Gel had a good shear response with excellent drug release characteristics under nearinfrared light, and increased intensity and duration of near-infrared light exposure enhanced Tmab release from the gel. Ce6-PC-Tmab@A-Gel was stable at room temperature and in a simulated tumor microenvironment (pH 6.25). Cytotoxicity assay (MTT) showed that Ce6-PC-Tmab@A-Gel combined with near-infrared light resulted in a survival rate of (31.37±1.73)% in SKBR-3 cells, much lower than that in the control group and other treatment groups (P < 0.01); the combined treatment also had a high efficiency of ROS production, and ROS release reached (22.36 ± 0.11)% after 2 min of near-infrared light exposure. OBJECTIVE: The prepared Ce6-PC-Tmab@A-Gel has good near-infrared light response release characteristics to ensure effective targeted therapy with Tmab. The injectable gel system potentially allows long-term local drug release in the tumor to improve the treatment efficacy against drug-resistant breast cancer.

The cholinergic system in joint health and osteoarthritis: a narrative-review.

Osteoarthritis (OA) poses a major health and economic burden worldwide due to an increasing number of patients and the unavailability of disease-modifying drugs. In this review, the latest understanding of the involvement of the cholinergic system in joint homeostasis and OA will be outlined. First of all, the current evidence on the presence of the cholinergic system in the normal and OA joint will be described. Cholinergic innervation as well as the non-neuronal cholinergic system are detected. In a variety of inflammatory diseases, the classic cholinergic anti-inflammatory pathway lately received a lot of attention as via this pathway cholinergic agonists can reduce inflammation. The role of this cholinergic anti-inflammatory pathway in the context of OA will be discussed. Activation of this pathway improved the progression of the disease. Secondly, chondrocyte hypertrophy plays a pivotal role in osteophyte formation and OA development; the impact of the cholinergic system on hypertrophic chondroblasts and endochondral ossification will be evaluated. Cholinergic stimulation increased chondrocyte proliferation, delayed chondrocyte differentiation and caused early mineralisation. Moreover, acetylcholinesterase and butyrylcholinesterase affect the endochondral ossification via an acetylcholine-independent pathway. Thirdly, subchondral bone is critical for cartilage homeostasis and metabolism; the cholinergic system in subchondral bone homeostasis and disorders will be explored. An increase in osteoblast proliferation and osteoclast apoptosis is observed. Lastly, current therapeutic strategies for OA are limited to symptom relief; here the impact of smoking on disease progression and the potential of acetylcholinesterase inhibitors as candidate disease-modifying drug for OA will be discussed.