Objective: Our study was aimed to construct a predictive model to advance ovarian cancer diagnosis by machine learning. Methods: A retrospective analysis of patients with pelvic/adnexal/ovarian mass was performed. Potential features related to ovarian cancer were obtained as many as possible.The optimal machine learning algorithm was selected among six candidates through 5-fold cross validation. Top 20 features having the most powerful predictive significance were ranked by Shapley Additive Interpretation (Shap) method. Clinical validation was further performed to confirm whether our model could advance diagnosis of ovarian cancer. Results: A total of 9,799 patients were collected. The inclusion criteria included age >18 years old, the first diagnosis being pelvic/adnexal/ovarian mass of undetermined significance, and pathological report indispensable. Four hundred and thirty-eight dimensional features were obtained after filtration. LightGBM showed the best performance with accuracy 88%.Among the top 20 features, 55% belonged to laboratory test report, 35% came from imaging examination report, and 10% were attributed to basic demographics and main symptom.Age, CA125, and risk of ovarian malignancy algorithm were the top three. Our predictive model performed stably in testing and clinical validation datasets, and was found to advance the diagnosis of ovarian cancer about 17 days before clinical pathological examination. Conclusion LightGBM was the optimal algorithm for our predictive model with accuracy of 88%. Laboratory test and imaging examination played essential roles in diagnosing ovarian cancer. Our model could advance the diagnosis of ovarian cancer before clinical pathological examination.

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

ObjectiveTo evaluate the effectiveness and consistency of three commonly used early colorectal cancer screening models for advanced colorectal adenoma as a noninvasive means， and to assess the predictive value of traditional Chinese medicine （TCM） tongue images in the models. MethodsPatients diagnosed with colorectal adenoma who underwent colonoscopy and pathological examination were selected as the study participants. Basic clinical data and tongue image were collected. The prediction models of Asia-Pacific colorectal screening （APCS） model， its revision （M-APCS） and colorectal neoplasia predict （CNP） model were applied to compare the predictive effects of the three models on advanced stage adenomas of the colon， the differences in clinical data and traditional Chinese medicine tongue characteristics among patients with different degrees of adenomas， and the similarities and differences in tongue characteristics among the models. The discriminative ability of the three risk models was evaluated using the area under the curve （AUC） and receiver operating characteristic （ROC） curves. The calibration was assessed using the Kuder-Richardson coefficient and the Hosmer-Lemeshow test for consistency analysis. ResultsA total of 227 patients with adenoma were analyzed， including 104 patients （45.82%） with advanced adenoma. In the detection of advanced adenoma， those with greasy coating （70 cases， 67.3%） were higher than those without greasy coating （34 cases， 32.7%， P＜0.05）. After multivariate analysis， the odds ratio （OR） value of non-greasy coating was 0.371 （0.204~0.673， P＜0.01）， indicating that non-greasy coating was a protective factor for advanced adenomas. Among the three risk models， the detection rate of advanced adenoma in the high-risk group with APCS was the highest （63.3%）， which was 1.49 times and 2.04 times that of the medium-risk group （42.6%） and the low-risk group （31.1%， P＜0.01）. The detection rate of advanced adenomas in high-risk groups of M-APCS and CNP was slightly higher than that in moderate or low risk groups （P＞0.05）. The proportion of yellow and greasy coating in high-risk group was higher than that in the medium-risk or low-risk group （P＜0.05）. For the ability to distinguish advanced and non-advanced adenomas， the AUC of APCS was 0.629 （95% CI： 0.556~0.702） and was higher than that of M-APCS （0.591） and CNP （0.586）. In calibration evaluation， Cronbach's alpha was 0.919 （＞0.7）， which indicated that the three models were consistent. In the correlation matrix， the correlation coefficients between APCS model and M-APCS model， and CNP model were 0.794 and 0.717， respectively， and the correlation coefficients between M-APCS model and CNP model were 0.873， Hosmer-Lemeshow χ² =2.552， P＞0.05， which suggested that the three models had good calibration ability. ConclusionAll three models demonstrate the efficiency to identify advanced colorectal adenoma， and their calibration ability is considered to be good. Among the three models， the APCS exhibits the highest recognition efficiency， however， the recognition accuracy of the APCS model needs improvement. The presence of a greasy coating is identified as one of the potential predictors of advanced adenoma. Consequently， it can be considered for inclusion in the risk model of advanced colorectal adenoma to enhance the accuracy.

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Objective: To carry out multipath cytogenetic analysis of a rare case of acute myeloid leukemia (AML) with 11q23 aberration and D13S319 deletion. Methods: G+ R banding technique was used to analyze the chromosomal karyotype of the patient after 24 h of cell culture. Combined interphase and metaphase fluorescence in situ hybridization (FISH) was used to detect specific chromosomal sites for complex translocations and minor missing fragments. Results: The patient was found to harbor MLL-AF10 fusion gene due to rearrangement of the mixed lineage leukemia (MLL) gene in conjunct with deletion of the D13S319 locus on chromosome 13. Conclusion Whether MLL gene rearrangement and absence of D13S319 locus has a double impact on AML should attract more attention. For AML patient with clonal abnormalities such as 13q-, del (13)(q14), -13 or der (13), FISH assay should be proof and considered to determine the size of missing fragment so as targeted therapy may be implemented.

Objective To evaluate clinical remission in patients with small bowel Crohn's disease (SBCD) who have received infliximab(IFX) therapy and to evaluate capsule endoscopy combined with ileocolonoscopy for mucosal healing at 14th week of IFX therapy.Methods Clinical data of 23 SBCD patients who received IFX were retrospectively analyzed.Laboratory indices [routine blood tests,C-reactive protein (CRP)and albumin],Crohn's disease activity index (CDAI),Lewis score (LS),Crohn's disease simplified endoscopic score (SES-CD),side effects and complications were compared before IFX treatment and at 14th week of IFX therapy.Results In 23 SBCD patients,both CDAI and CRP levels significantly decreased (P＜0.01) while body mass index (BMI) and albumin levels increased at 14th week (P＜0.05),compared with those before treatment.The clinical remission rate at 14th week was 91.3％ (21/23).There were 8/23 (34.8％)SBCD patients achieving mucosal healing in small bowel,12/21 (57.1％) in terminal ileum and colon,and 7/21 (33.3％) in both small bowel and colon.Twelve patients achieved both clinical remission and biochemical remission at 14th week and all of them achieved mucosal healing in both terminal ileum and colon (SES-CD ≤ 2).However,there were 5 (41.7％) of them still with small bowel inflammation (LS＞ 135).Conclusion IFX plays a role in promoting clinical remission and mucosal healing in SBCD patients.Mucosal healing of CD patients in terminal ileum and other parts of small intestine are not synchronized.For CD patients with small bowel and colon involved,the evaluation of the whole gastrointestinal tract by capsule endoscopy combined with ileocolonoscopy is recommended on condition that they have no intestinal obstruction or severe stricture.

The objective of the present study was to establish a method based on principal component analysis (PCA) for the study of transdermal delivery of multiple components in Chinese medicine, and to choose the best penetration enhancers for the active fraction of Xiangfusiwu decoction (BW) with this method. Improved Franz diffusion cells with isolated rat abdomen skins were carried out to experiment on the transdermal delivery of six active components, including ferulic acid, paeoniflorin, albiflorin, protopine, tetrahydropalmatine and tetrahydrocolumbamine. The concentrations of these components were determined by LC-MS/MS, then the total factor scores of the concentrations at different times were calculated using PCA and were employed instead of the concentrations to compute the cumulative amounts and steady fluxes, the latter of which were considered as the indexes for optimizing penetration enhancers. The results showed that compared to the control group, the steady fluxes of the other groups increased significantly and furthermore, 4% azone with 1% propylene glycol manifested the best effect. The six components could penetrate through skin well under the action of penetration enhancers. The method established in this study has been proved to be suitable for the study of transdermal delivery of multiple components, and it provided a scientific basis for preparation research of Xiangfusiwu decoction and moreover, it could be a reference for Chinese medicine research.

Objective To investigate the relationship between type-2 diabetes mellitus and artery atherosclerosis(AS) in the elderly. MethodsThe clinical data of 277 elders,who were admitted in hospital between April 2005 and September 2007, were retrospectively analyzed. These elders were divided into four groups: type 2 diabetes with carotid atherosclerosis (CAS) group (group A, n=119), type 2 diabetes without CAS group (group B, n= 30), non-diabetic with CAS group (group C, n=32), non-diabetic without CAS group (group D, n=96). The correlation between carotid artery plaque and related factors were studied. Results① Compared with group C,fasting blood glucose[(7.14±2.49) mmol/L vs. (5.21±0.87) mmol/L], triglycefide [(1.41±0.78) mmol/L vs. (0.95±0.39) mmol/L],left and right common carotid artery IMT [(0.85±0.11) nun vs. (0.79±0.08) mm, (0.85±0.11)mm vs. (0.78±0.09)mm] and PI [(1.37±1.16) vs. (0.50±0.80)] of group A were significantly increased, while high density lipoprotein [(1.29±0.32) mmol/L vs. (1.58±0.45) mmol/L] is significantly decreased(P=0.01). ②Compared with group B, left and right common carotid artery IMT [(0.85±0.11) mm vs. (0.80±0.11)mm,(0.85±0.11)mm vs. (0.80±0.12)mm,PI[(1.37±1.16) vs. (0.00±0.00)]and incidence of stroke 34.5% (41/119) vs. 13.3% (4/30) of group A are significantly increased (P<0.05 or P<0.01). ③Carotid artery plaque was positively correlated with history of diabetes(r=0.051, P<0.01),hypertension(r= 0.169,P<0.01),coronary heart disease (r=0.109,P<0.05),stroke(r=0.136,P<0.05),fatty liver(r= 0.340,P<0.01),FBG(r=0.339,P<0.01),TG(r=0.195,P<0.01),APOB (r=0.152,P<0.05),but negatively correlated with HDL-C (r=-0.143, P<0.05). Conclusion The risk of AS is higher in elderly patients with type 2 diabetes than that of non-diabetes. The incidence of stroke is higher in type 2 diabetes with AS than those of type 2 diabetes without AS. Carotid artery plaque is positively correlated with diabetes, hypertension, history of coronary heart disease, history of stroke, fatty liver, FBG, TG, ApoB, but negatively correlated with HDL-C.