Perfusion-weighted imaging with dynamic contrast enhancement (PWI/DCE) morphologic, qualitative, semiquantitative, and radiomics features predicting undifferentiated pleomorphic sarcoma (UPS) treatment response.

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from time-intensity curves (TICs), and 107 radiomic features were derived. Statistical analyses compared R vs. PR/NR. At PRT, 79% of R displayed a "Capsular" morphology (P = 1.49 × 10-7), and 100% demonstrated a TIC-type II (P = 8.32 × 10-7). 80% of PR showed "Unipolar" morphology (P = 1.03 × 10-5), and 60% expressed a TIC-type V (P = 0.06). Semiquantitative wash-in rate (WiR) was able to separate R vs. PR/NR (P = 0.0078). The WiR radiomics displayed significant differences in the first_order_10 percentile (P = 0.0178) comparing R vs. PR/NR at PRT. The PWI/DCE TIC-type II curve, low WiR, and "Capsular" enhancement represent PRT patterns typically observed in successfully treated UPS and demonstrate potential for UPS treatment response assessment.

[An MRI multi-sequence feature imputation and fusion mutual-aid model based on sequence deletion for differentiation of high-grade from low-grade glioma].

OBJECTIVE: To evaluate the performance of magnetic resonance imaging (MRI) multi-sequence feature imputation and fusion mutual model based on sequence deletion in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). METHODS: We retrospectively collected multi-sequence MR images from 305 glioma patients, including 189 HGG patients and 116 LGG patients. The region of interest (ROI) of T1-weighted images (T1WI), T2-weighted images (T2WI), T2 fluid attenuated inversion recovery (T2_FLAIR) and post-contrast enhancement T1WI (CE_T1WI) were delineated to extract the radiomics features. A mutual-aid model of MRI multi-sequence feature imputation and fusion based on sequence deletion was used for imputation and fusion of the feature matrix with missing data. The discriminative ability of the model was evaluated using 5-fold cross-validation method and by assessing the accuracy, balanced accuracy, area under the ROC curve (AUC), specificity, and sensitivity. The proposed model was quantitatively compared with other non-holonomic multimodal classification models for discriminating HGG and LGG. Class separability experiments were performed on the latent features learned by the proposed feature imputation and fusion methods to observe the classification effect of the samples in twodimensional plane. Convergence experiments were used to verify the feasibility of the model. RESULTS: For differentiation of HGG from LGG with a missing rate of 10%, the proposed model achieved accuracy, balanced accuracy, AUC, specificity, and sensitivity of 0.777, 0.768, 0.826, 0.754 and 0.780, respectively. The fused latent features showed excellent performance in the class separability experiment, and the algorithm could be iterated to convergence with superior classification performance over other methods at the missing rates of 30% and 50%. CONCLUSION: The proposed model has excellent performance in classification task of HGG and LGG and outperforms other non-holonomic multimodal classification models, demonstrating its potential for efficient processing of non-holonomic multimodal data.

[Clinical effect of modified anterolateral acromioplasty in rotator cuff repair under shoulder arthroscope].

Objective: To compare the clinical effect of modified anterolateral and traditional acromioplasty in arthroscopic rotator cuff repair. Methods: The clinical data of 92 patients with total rotator cuff tears admitted to the Department of Joint Surgery of Jinhua Central Hospital from January 2016 to December 2019 were retrospectively analyzed. Of the patients, 42 were male, 50 were female, with a mean age of (57.1±13.2) years. Among them, 42 patients underwent traditional acromioplasty during arthroscopic rotator cuff repair (traditional group), and 50 underwent modified anterolateral acromioplasty (modified group). The preoperative and postoperative shoulder function of the patients in the two groups were evaluated and compared by using the University of California Los Angeles (UCLA), the rating scale of the American Shoulder and Elbow Surgeons (ASES), and the constant Murley shoulder score scale. And the preoperative and postoperative pain of patients was evaluated with visual analog scale (VAS). The incidence of rotator cuff retears 12 months after operation was counted. Results: There was no statistically significant differences in general information such as gender, age, affected side and course of disease between the two groups before the surgery (all P<0.05). All patients were followed up for (12.9±1.1) months. There was no significant differences in the UCLA score (31.4±3.0 vs 32.0±2.5), ASES score (13.1±0.7 vs 13.3±0.6), Constant Murley shoulder score (92.1±6.6 vs 94.3±4.6) and VAS score (1.5±0.8 vs 1.2±1.1) between the traditional group and the modified group 12 months after the operation (all P>0.05). The preoperative CSA (36.0°±1.7°) in the traditional group did not differ significantly from that at 12 months postoperatively (35.5°±1.2°) (P=0.270); the postoperative CSA at 12 months (30.8°±2.5°) in the modified group was significantly smaller than that before the operation (36.5°±1.9°), and also was smaller than that in the traditional group 12 months after the operation (35.5°±1.2°) (both P<0.05). At 12 months after operation, the rate of rotator cuff tears in the traditional group and modified group was 16.7% (7/42) and 4.0% (2/50), respectively (P=0.045). Conclusions: Traditional and modified anterolateral acromioplasty in treating total rotator cuff tears using arthroscopic rotator cuff repair can significantly improve shoulder joint function. However, modified anterolateral acromioplasty significantly reduces the CSA value and decreases the incidence of rotator cuff re-tears.

Lattice distortion enabling enhanced strength and plasticity in high entropy intermetallic alloy.

Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.

[Therapeutic efficacy of transoral robotic surgery with the da Vinci robot system for the treatment of oropharyngeal squamous cell carcinoma].

Objective: To evaluate the clinical efficacy of transoral robotic surgery (TORS) with the da Vinci robot system in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Methods: A mixed cohort study was conducted to collect and analyze the clinical data of OPSCC patients who underwent TORS at the Eye & ENT Hospital, Fudan University between July 2020 and February 2023 (TORS group). OPSCC patients who underwent conventional surgery between January 2016 and September 2020 were included as the control group. The baseline information, incidence of complications and follow-up data were compared between the two groups. Results: A total of 166 patients were included, with 102 cases (81 males and 21 females) in the TORS group [mean age: (59.1±9.8) years] and 64 cases (54 males and 10 females) in the control group [ mean age: (57.6±9.7) years]. Compared with the control group, the TORS group had lower postoperative bleeding rate [2.9% (3/102) vs 10.9% (7/64), P=0.035] and infection rate [1.0% (1/102) vs 18.8% (12/64), P<0.001]. No statistically significant differences were observed in tracheotomy rate [46.1% (47/102) vs 59.4% (38/64), P=0.070] and median length of hospital stay [8 (7, 10) d vs 10 (4, 12) d, P=0.088]. After propensity score matching, compared with the control group, the TORS group had lower postoperative infection rate [0 (0/31) vs 19.4% (6/31), P=0.032] and median length of hospital stay [7 (7, 10) d vs 10 (8, 12) d, P=0.031]. No statistically significant differences were found in postoperative bleeding rate [3.2% (1/31) vs 6.5% (2/31), P=1.000] and tracheotomy rate [22.6% (7/31) vs 45.2% (14/31), P=0.060] between the two groups. Moreover, 1-and 2-year disease-free survival rates were 96.3% and 94.6% in the TORS group, and 90.6% and 84.3% in the control group, respectively (P=0.233). The 1-and 2-year cancer-specific survival rates were both 100% in the TORS group, and 96.9% and 93.8% in the control group, respectively (P=0.539). Conclusion: TORS for OPSCC is associated with high clinical safety and favorable oncological outcomes.

[Long-term outcomes of lower extremity arteriovenous grafts].

Objective: To evaluate the long-term outcomes of lower extremity arteriovenous graft (AVG) in hemodialysis patients. Methods: Hemodialysis patients with lower extremity AVG from August 2015 to July 2023 in the Department of Vascular Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine were enrolled. Therapeutic effects and complications of AVG were retrospectively analyzed. Results: A total of 83 cases aged (58.9±13.3) years were enrolled, including 25 males and 58 females. The success rate of the operation was 100% (83/83), and no perioperative complications occurred. The follow-up time [M (Q1, Q3)] was 38.4 (22.6, 55.3) months, with a follow-up rate of 92.8% (77/83). There were 9 cases (11.7%) of puncture site infection, 5 cases (6.5%) of pseudoaneurysm, 2 cases (2.6%) of seroma, 3 cases (3.9%) of lower limb ischemia, 48 cases (62.3%) of stenosis and 24 cases (31.2%) of thrombosis during the follow-up period. The 6-month, 1-year, 2-year, 3-year and 5-year primary patency rates after surgery were 78.9%, 61.2%, 39.0%, 27.0% and 16.3%, respectively, assisted primary patency rates were 93.5%, 82.5%, 74.9%, 68.0% and 53.0%, respectively, and secondary patency rates were 96.1%, 94.7%, 93.1%, 91.3% and 75.3%, respectively. Conclusion: For patients whose vascular resources of upper limbs are exhausted, lower extremity AVG is a safe and effective hemodialysis vascular access.

[Modification of allergic dermatitis on the associations between early-life exposure to size-specific particulate matter and childhood allergic rhinitis].

To evaluate the modification of allergic dermatitis on the association between PM exposure and allergic rhinitis in preschool children. This cross-sectional study was based on a questionnaire conducted between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in the kindergartens of 7 Chinese cities to collect information on allergic rhinitis and allergic dermatitis. A mature machine learning-based space-time extremely randomized trees model was applied to estimate early-life, prenatal, and first-year exposure of PM1, PM2.5 and PM10 at 1 km×1 km resolution. A combination of multilevel logistic regression and restricted cubic spline functions was used to quantitatively assess whether allergic dermatitis modifies the associations between size-specific PM exposure and the risk of childhood allergic rhinitis. The results showed that out of 28 408 children, 14 803 (52.1%) were boys and 13 605 (47.9%) were girls; the age of children ranged from 3.1 to 6.8 years, with a mean age of (4.9±0.9) years, of which 3 586 (12.6%) were diagnosed with allergic rhinitis. Among all children, 17 832 (62.8%) were breastfed for more than 6 months and 769 (2.7%) had parental history of atopy. A total of 21 548 children (75.9%) had a mother with an educational level of university or above and 7 338 (29.6%) had passive household cigarette smoke exposure. The adjusted ORs for childhood allergic rhinitis among the children with allergic dermatitis as per interquartile range (IQR) increase in early-life PM1(9.8 µg/m3), PM2.5 (14.9 µg/m3) and PM10 (37.7 µg/m3) were significantly higher than the corresponding ORs among the children without allergic dermatitis [OR: 1.45, 95%CI (1.26, 1.66) vs. 1.33, 95%CI (1.20, 1.47), for PM1; OR: 1.38, 95%CI (1.23, 1.56) vs. 1.32, 95%CI (1.21, 1.45), for PM2.5; OR: 1.56, 95%CI (1.31, 1.86) vs. 1.46, 95%CI (1.28, 1.67), for PM10]. The interactions between allergic dermatitis and size-specific PM exposure on childhood allergic rhinitis were statistically significant (Z value=19.4, all P for interaction<0.001). The similar patterns were observed for both prenatal and first-year size-specific PM exposure and the results of the dose-response relationship were consistent with those of the logistic regression. In conclusion, allergic dermatitis, as an important part of the allergic disease progression, may modify the association between ambient PM exposure and the risk of childhood allergic rhinitis. Children with allergic dermatitis should pay more attention to minimize outdoor air pollutants exposure to prevent the further progression of allergic diseases.

[A preliminary study on the characteristics of refractive parameters and retinal blood flow in dominant eyes].

Objective: To explore the characteristics of refractive parameters and retinal and choroidal blood flow in dominant and non-dominant eyes. Methods: A cross-sectional study. Students who were 18 to 32 years old and had emmetropia or myopia but no systemic diseases were recruited from universities in Wuhu, Anhui Province from April 2019 to August 2023. They were divided into 4 groups based on the difference in spherical equivalent between two eyes:<0.50 D (group A), 0.50 to 1.74 D (group B), 1.75 to 2.49 D (group C), and≥2.50 D (group D). The card hole method was used to determine the dominant eye. The refractive parameters of both eyes were recorded, including spherical equivalent, myopia degree, astigmatism degree, axial length, and corneal curvature difference (K2-K1). Optical coherence tomography angiography was performed to measure the blood flow density of the superficial retinal capillaries, deep retinal capillaries (DVC), avascular layer (AC), entire retina, choroidal capillaries, and choroidal vessels, as well as the retina and choroid as a whole. Statistical analysis was conducted using the paired sample t-test, chi square test, and variance analysis. Results: A total of 78 eligible subjects, aged (24.50±2.36) years old, 28 males and 50 females, were included. Fifty subjects had the right eye and 28 had the left eye as the dominant eye. Forty-two subjects had high myopia in the dominant eye, and 30 had high myopia in the non-dominant eye. There were statistically significant differences (all P<0.05) in the spherical equivalent [(-4.588±2.534) D vs. (-4.058±2.453) D], myopic spherical power [(-4.253±2.504) D vs. (-3.779±2.425) D], and axial length [(25.531±1.212) mm vs. (25.256±1.238) mm] between dominant and non-dominant eyes among all subjects, as well as in the astigmatism degree of groups A and C, spherical power of groups B to D, and spherical power and axial length of groups C and D. There were also statistically significant differences (all P<0.05) in the blood flow density of the DVC [(0.291±0.130) vs. (0.257±0.148)], AC [(0.347±0.118) vs. (0.326±0.126)], and overall retina and choroid [(0.385±0.102) vs. (0.349±0.084)] between dominant and non-dominant eyes among all subjects, as well as in the blood flow density of the superficial retinal capillaries, DVC, AC, choroidal capillaries, and overall retina and choroid of groups C and D, density of the choroidal vessels of group C, and density of the entire retina of group D. Conclusions: In young individuals with emmetropia or near vision, the degree of myopia in dominant eyes is higher than that in non-dominant eyes. When the difference in the spherical equivalent between two eyes is ≥1.75 D, the blood flow density of the retina and choroid in the dominant eye is greater than that in the non-dominant eye.

[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure.

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

[Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms].

Objective: To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP. Methods: Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software. Results: Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences (P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion: This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

Assessing morinidazole for surgical site infection in class III wounds prevention: a multi-centre, randomized, single-blind, parallel-controlled study.

INTRODUCTION: Surgical site infections (SSIs) are significant postoperative risks; antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class III wounds, as there is currently a lack of evidence in the existing literature. METHODS: A multi-centre randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China, including 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. RESULTS: A total of 440 participants (median (interquartile range, IQR) age, 63.0 (54.0, 70.0) years; 282 males (64.09%); 437 patients were of Han race (99.32%) and were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 (14.49%) vs 52 (23.01%); risk difference, 1.76%, 95% confidence interval (CI) 1.08-2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 (5.61%) vs 31 (13.37%); risk difference, 2.68%; 95% CI 1.34-5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). CONCLUSION: The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole to be a valuable prophylactic antibiotic. Our findings provide valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.

[Optimal melanin removal methods for HE staining, immunohistochemistry and molecular detection].

Objective: To seek the optimal melanin-removal method for hematoxylin and eosin (HE) staining, immunohistochemistry and molecular detection. Methods: Thirty-eight paraffin tissue samples of malignant melanoma diagnosed at the Fujian Cancer Hospital, Fuzhou, China between January 2018 and March 2022 were collected and used to make a tissue microarray. Melanin in these cases was removed using warm hydrogen peroxide, double oxidation depigmentation, modified potassium permanganate-oxalic acid or trichloroisocyanuric acid, followed by HE staining. The cases were divided into two cohorts: one was subject to the one of the above four methods to remove melanin first, followed by immunohistochemistry (SOX-10, Ki-67, HMB45 and Melan A), while the other was subject to immunohistochemical staining first and then a melanin removal. Following that, seventeen melanin-rich paraffin tissue samples were collected and depigmented using the methods described above. DNA extraction was then done, followed by assessments of DNA content and quality. Moreover, the completeness of melanin removal, the effect on HE and immunohistochemical staining, and the quality of DNA were compared between the depigmented methods. Results: Regarding the effectiveness of melanin removal, the modified potassium permanganate-oxalic acid and the warm hydrogen peroxide methods were the most effective, and both showed residual melanin in only 5.26% (2/38) of the cases. The trichloroisocyanuric acid method showed residual melanin in 10.53% (4/38) of the cases. The worst was the double oxidation depigmentation method, which showed pigment residue in 15.79% (6/38) of the cases. For HE staining, the percentage of good staining with the warm hydrogen peroxide method was 92.11%, higher than the other three methods. For immunohistochemical staining, the mean staining scores of immunohistochemistry first followed by melanin removal with modified potassium permanganate-oxalic acid, double oxidation and trichloroisocyanuric acid were 20.84, 26.63 and 35.02, respectively. These immunohistochemical staining scores were higher than those of melanin removal first followed by immunohistochemistry (8.70, 15.41 and 21.22, respectively). The mean staining score of melanin removal by warm hydrogen peroxide method followed by immunohistochemistry was 33.57, superior to that of immunohistochemistry followed by the melanin removal (19.96). Moreover, the staining scores of HMB45, MelanA and Ki-67 with immunohistochemical staining followed by trichloroisocyanuric acid method were 36.45, 33.79, and 36.24, respectively, while the staining score of SOX10 with melanin removal by warm hydrogen peroxide followed by immunohistochemistry was 34.39. The DNA was significantly degraded by modified potassium permanganate-oxalic acid, double oxidation depigmentation and trichloroisocyanuric acid, whereas the mean concentration of DNA extracted after melanin removal by hydrogen peroxide method was 59.59 µg/L, substantially higher than that of DNA extracted without melanin removal (30.3 µg/L, P=0.001). The A260/A280 of DNA extracted after melanin removal by hydrogen peroxide was between 1.8 and 2.0 in all cases, and the A260/A230 was above 2.0 in sixteen cases, suggesting high purity of DNA. However, the DNA extracted without removing the melanin showed poor purity, with A260/A280 below 1.8 in eight cases and A260/A230 below 2.0 in sixteen cases. Conclusions: Warm hydrogen peroxide showed the least melanin residue, superior HE staining and a minimal effect on DNA purity/quality compared to the other three methods. It thus appears most suitable for PCR, NGS and other molecular detection. Melanin removal with trichloroisocyanuric acid after immunohistochemical staining has the least melanin residual, and thus could be the most convenient and efficient. However, it is noted that the efficacy of the same depigmentation method varies with different antibodies. Therefore, the optimal depigmentation method should be selected based on the specific markers of interest.

Relationship between mandibular third molars and mandibular angle and condylar fractures.

BACKGROUND: Assess the correlation between the position of the third molar (M3) and fractures of the mandibular angle and condyle using panoramic radiographs to offer valuable data references for oral clinical research. MATERIAL AND METHODS: A retrospective cross-sectional study was undertaken, involving the collection of 409 cases of mandibular fracture in the Yanbian University Hospital. The case records and panoramic radiographs of mandibular angle fracture (78 cases) and condylar fracture (106 cases) were evaluated. RESULTS: In the comparative analysis between the mandibular angle fracture group and the condylar fracture group, statistical significance was observed in the variables of M3 existence (P = 0.002), eruption of M3 from the alveolar cavity (P = 0.003), P&G position classification (P = 0.001), deep impactions (Classes IC, IIC, IIIB, and IIIC) (P < 0.001), and the presence of impacted M3 in both groups (P < 0.001).Regarding M3 roots, the mandibular angle fracture group exhibited the highest prevalence of multiple roots at 75.4%, surpassing the 64.6% observed in the condylar fracture group. The prevalence of proximal angles in the mandibular angle group and the condyle group was the highest, accounting for 64.6% and 61.5%, respectively. The percentage of M3 in the two groups was 80% and 43.1%, respectively, with a significant difference (P < 0.001). CONCLUSIONS: Impacted mandibular third molars (M3) elevate the risk of mandibular angle fractures, while their absence or normal eruption reduces this risk and protects against condylar process fractures. The fracture risk is influenced by the M3's position: P&G Class II and Class B impactions, where M3s emerge partially from the alveolar bone, are significantly associated with mandibular angle fractures. In contrast, the absence of M3 or its placement in P&G Class I and Class A positions tends to correlate with a higher incidence of condylar process fractures.

Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

Sex-Related Differences in Dispensation of Rheumatic Medications in Older Patients With Inflammatory Arthritis: A Population-Based Study.

OBJECTIVE: The aim of our study was to compare dispensation of rheumatic medications between older male and female patients with early rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: This retrospective cohort study was performed using health administrative data from Ontario, Canada (years 2010-2017), on patients with incident RA and PsA, who were aged ≥ 66 years at the time of diagnosis. Yearly dispensation of rheumatic drugs was compared between older male and female patients for 3 years after diagnosis using multivariable regression models, after adjusting for confounders. The groups of drugs included in the analysis were disease-modifying antirheumatic drugs (DMARDs) classified as conventional synthetic DMARDs (csDMARDs) and advanced therapy (biologic DMARDs and targeted synthetic DMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and oral corticosteroids. Results were reported as odds ratios (ORs) with 95% CIs. RESULTS: We analyzed 13,613 patients (64% female) with RA and 1116 patients (57% female) with PsA. Female patients with RA were more likely to receive opioids (OR 1.39, 95% CI 1.22-1.58 to OR 1.51, 95% CI 1.32-1.72) and NSAIDs (OR 1.14, 95% CI 1.04-1.25 to OR 1.16, 95% CI 1.04-1.30). Dispensation of DMARDs showed no sex difference in either group. Subgroup analyses showed more intense use of advanced therapy in the RA cohort and of csDMARDs in the PsA cohort when patient and physician sex was concordant. CONCLUSION: This study did not identify any sex difference in the use of DMARDs among older patients with RA and PsA. The reasons for the higher use of opioids and NSAIDs among female patients with RA warrant further research.

[Chronic myeloid leukemia with e6a2 fusion gene: a case report and literature review].

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

Evaluation of residual bone mass of the mandibular third molar and the risk of mandibular fracture.

BACKGROUND: A quantification of the residual bone mass of the mandible (B/A) was utilized in this study to examine the correlation between mandibular fracture and residual bone mass. To improve the clinical utilization rate and reduce the incidence of iatrogenic mandibular fractures, the B/A ratio calculation should be simplified. MATERIAL AND METHODS: Data were collected from the Yanbian University Hospital on 175 cases of mandibular fracture with third molar (M3), 67 normal cases without fractures and 20 cases of impacted teeth extraction. Twenty cases of iatrogenic mandibular fracture were collected, and the case records and panoramic radiographs of the patients were recorded. RESULTS: The average B/A ratio of mandibular angle fracture group was 0.61±0.10.The value of B/A was found to be statistically significant in terms of whether M3 emerged from alveolar bone (P = 0.001), location (horizontal P < 0.001, vertical P < 0.001), the degree of impaction (P < 0.001), the number of roots (P < 0.001), the difference in impaction (P < 0.001), and the fracture type (P = 0.002). The average B/A ratio of normal group was 0.62±0.10. In the statistical results of the B/A value of normal patients, M3 involving alveolar bone (P < 0.001), position classification (P < 0.05), degree of impaction (P < 0.001) and presence or absence of a root (P < 0.05) were statistically significant. The average B/A ratio of iatrogenic mandibular angle fracture group was 0.28±0.08. The average B/A ratio of the extraction group for impacted teeth was 0.62 ± 0.09. CONCLUSIONS: There is a high risk of mandibular angle fracture when the (B/A) value of the residual bone height (B) in the mandibular M3 area compared to the mandibular bone height (A) in the M3 area is less than 0.4.

[New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients].

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.