[Diagnosis and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement].

Objective: To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis. Methods: The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted. Results: Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months. Conclusions: Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.

Risk factors for infection in patients undergoing shoulder arthroscopy: a systematic review and meta-analysis.

We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled odds ratios (ORs), based on sample size, the P-value of Egger's test and heterogeneity among studies. Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% confidence interval (CI), 1.20-1.41) or hypertension (OR, 1.26; 95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (body mass index ≥30 kg/m2) (OR, 1.42; 95% CI, 1.28-1.57), those who were male (OR, 1.65; 95% CI, 1.12-2.44), those who had an American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.02; 95% CI, 1.02-3.99) and those who had a history of smoking (OR, 2.44; 95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy.

Effects of dietary camelina, flaxseed, and canola oil supplementation on plasma fatty acid concentrations and health parameters in horses.

Camelina (Camelina sativa) is a hardy, low-input oilseed crop that provides a rich source of the n-3 fatty acid, α-linolenic acid (ALA). The primary purpose of the present study was to assess the effects of dietary camelina oil (CAM) consumption on various health parameters, as compared to horses fed canola oil (OLA) or flax oil (FLX). Secondly, to determine how dietary CAM, FLX, and OLA alter circulating plasma total lipids across time. Thirty horses, from three separate herds, were used for this study [14.9 years ± 5.3 years; 544 ± 66 kg calculated BW (mean ± SD)]. After a 4-week gradual acclimation period using sunflower oil mixed with soaked hay cubes, horses were balanced by location, age, sex, weight, and breed and randomly allocated to one of three treatment oils (CAM, OLA, or FLX) at an inclusion of 370 mg of oil/kg BW/day. Horses had ad libitum access to hay and/or pasture for the duration of the study. Body condition score (BCS), BW, oil intake, complete blood counts, plasma biochemical profiles, and plasma total lipids were measured on weeks 0, 2, 4, 8, and 16 throughout the 16-week treatment period. BW, BCS, and oil intake were analyzed using an ANOVA using PROC GLIMMIX in SAS Studio. Complete blood counts and biochemical profiles were analyzed using an ANCOVA, and fatty acids were analyzed using an ANOVA in PROC MIXED in SAS Studio. No differences were observed among treatment groups for BW, BCS, oil intake, complete blood counts, and biochemical parameters. Individual fatty acids that differed among treatments and/or across time were largely reflective of the different FA profiles of the oils provided. Most notably, plasma ALA was greater for FLX than OLA, but neither differed from CAM (P = 0.01). Linoleic acid did not differ among treatments or over time (P > 0.05). The n-6:n-3 ratio decreased over time for both CAM and FLX, and ratios were lower for FLX than OLA at week 16, but not different from CAM (P = 0.02). These results suggest that dietary CAM had no adverse effects on health parameters and that daily supplementation of CAM and FLX at 370 mg of oil/kg BW/day induces positive changes (a decrease) in the n-6:n-3 status of the horse. Consequently, CAM may be considered as an alternative oil to FLX in equine diets.

[Analysis of clinicopathological features and prognosis of sporadic synchronous multiple primary colorectal cancers].

Objective: To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis. Methods: The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result: Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III-IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ2=6.293,P=0.043). The proportions of TNM Stage III-IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ2=13.994,P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ2=10.457,P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ2=5.086,P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ2=19.791,P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ2=4.601,P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ2=11.996,P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ2=7.643, P=0.006), had a higher proportion of TNM Stage III-IV disease (60.2% [100/166] vs. 24.2% [8/33], χ2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively (P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS (P=0.026). Conclusions: Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Subzero saline chilling with or without prechilling in icy water improved chilling efficiency and meat tenderness of broiler carcasses.

Freshly slaughtered carcasses need to be chilled to improve product quality, meat safety, and processing efficiency. This research investigated the effect of subzero saline chilling (SSC) on broiler carcasses with or without prechilling in icy water. Water immersion chilling at 0.5°C (WIC) or SSC at 4% NaCl/-2.41°C (SSC) was a major chilling step. For the combination of pre- and postchilling, the warm water immersion chilling (WWIC) at 10°C was used as prechilling and the WIC as postchilling (WWIC-WIC), and WIC was used as prechilling and the SSC as postchilling (WIC-SSC). The internal temperature of breast fillets was monitored during chilling. Carcasses in a prechiller were transported to a postchiller when their internal temperature reached 15°C. Chilling was completed when the carcass temperature reached 4.4°C or below, and breast fillets were harvested at 3-h postmortem to measure the pH and sarcomere length. Color (L*, a*, and b*) values were evaluated on both breast skin and skinless breast surfaces. Meat tenderness was evaluated using the breast fillets after overnight storage and cooking to an internal temperature of 76°C. The carcasses in the SSC and WIC-SSC showed shorter chilling times (85-91 min) than those (100-144 min) of WIC and WWIC-WIC. A higher chilling yield was observed for the carcasses in WIC-SSC, and a lower cooking yield was seen for the carcasses in WWIC-WIC than other chilling methods (P < 0.05). The breast fillets of broilers in the SSC and WIC-SSC showed lower shear forces and longer sarcomere length than the WIC and WWIC-WIC. No difference was found for L* and a* values, while lower b* value was observed in the SSC than the other chilling methods (P < 0.05). Based on these results, chilling of broiler carcasses in the SSC (4% NaCl/-2.41°C) with or without prechilling in WIC at 0.5°C significantly improved chilling efficiency and meat tenderness, with minor color changes on carcasses.

[Expression of MSI1 and HER2 in mammary Paget's disease and their correlation with clinicopathological features and prognosis].

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.

The effect of phacoemulsification on visual function among Filipino cataract patients measured by a validated Filipino translation of Catquest-9SF.

BACKGROUND: This study developed a validated Filipino version of the Catquest-9SF and administered it to cataract patients pre- and post- surgery. METHODS: This is a two-phase, single-center, cross sectional, questionnaire type study. The study included participants decked for surgery who are 18 years and above. Sampling was done purposively. The Catquest-9SF questionnaire was translated into Filipino, according to a standard procedure, and validated. The validated version was administered to the participants before and after unilateral cataract surgery. Data were analyzed using Rasch analysis. RESULTS: Sixty-one patients were enrolled in the study. The preliminary Rasch analysis showed misfit of item 2, which was subsequently excluded from analysis. The remaining eight items showed person separation index of 2.70, reliability coefficient of 0.88, infit of 0.66 to 1.17, outfit of 0.66 to 1.49, observed raw variance explained by measures of 55.3% and eigenvalues of 1.9, 1.4, 1.2, 1.0 and 0.9. There was slightly poor targeting (mean person location 1.24) and multidimensionality but no evidence of differential item functioning (DIF). High internal consistency of items were observed (Cronbach's alpha ≥ 90). Comparison of responses between pre- and post-surgery showed highly significant marginal homogeneity (p < 0.001). CONCLUSION: The Filipino translation of Catquest-9SF, the Catquest-8SF-PH, was highly valid. It showed improved perceived visual outcomes among Filipino patients post-cataract surgery.

30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Comparison of faculty and student evaluations of the hybrid teaching of orthopedics during the COVID-19 pandemic

Background@#In the face of the COVID-19 pandemic and a country-wide lockdown, the University of the Philippines College of Medicine halted face-to-face teaching in exchange for online learning for its students. For the Learning Unit VI students, clinical rotations shifted to hybrid activities to continue learning activities while minimizing exposure risk. The Philippine General Hospital Department of Orthopedics introduced the following hybrid activities in its curriculum for Learning Unit VI students: 1) Online Lectures, 2) Online Departmental Conference, 3) Online Division Rounds, 4) Online SGDs, 5) Written Case, 6) Online Exams, 7) Preceptorship, Demo, Return Demo, and 8) Online OSCE. The department used a variety of platforms including synchronous sessions, asynchronous pre-recorded lectures, and face-to-face teaching, as appropriate. @*Objectives@#The study compared the faculty and student course evaluations of activities in the hybrid ORTHO 251 course. @*Methodology@#Faculty and students were asked to evaluate each activity according to the Course Evaluation By Students (CEBS), the standard questionnaire used by the college, to determine the overall rating of each activity as well as any differences between the two groups. @*Results@#The hybrid activities conducted in the ORTHO 251 course were rated as good or excellent by the faculty and students, with differences in a few activities. Consultants rated online exams as being less effectively integrated and that there was inadequate time allotment for online SGDs, written cases, and online exams. Meanwhile, students rated all activities higher in terms of stimulating self-directed learning. @*Conclusion@#With good to excellent outcomes, this study found that it has at least satisfactorily matched the learning platform to the learning component. While knowledge may be taught via asynchronous recorded lectures or reading materials, attitude and thinking processes are better formed through synchronous discussion. Skills in medical education, including Orthopedics, are still best taught via face-to-face demoreturn demo. With this information, the department can investigate the causes of these differences and improve on the identified weaknesses.

Translation and validation of the Tagalog trust in ophthalmologist scale

Objective@#This study adapted and translated the Trust in Oncologist Scale (TiOS) into the Tagalog Trust in Ophthalmologist Scale (TTOS) and validated the latter.@*Methods@#The 18-item TiOS questionnaire was translated into Tagalog and validated in a cohort of 200 Filipino ophthalmology patients of a single institution. Internal consistency, construct validity, and test-retest reliabilities were determined. Exploratory factor analyses were also performed.@*Results@#The TTOS showed high internal consistency with Cronbach alpha of 0.92, high reliability with Pearson's coefficient of 0.85, and high validity with Spearman’s coefficient of 0.67.@*Conclusion@#The TTOS is a valid and reliable tool to measure the level of trust of Filipino patients in their ophthalmologists.

[Comparative study on imaging and clinical results of patellofemoral joint with kinematic alignment and mechanical alignment in total knee arthroplasty].

Objective: To investigate the changes of imaging parameters of patellofemoral joint after kinematic alignment total knee arthroplasty (KA-TKA) and mechanical alignment total knee arthroplasty (MA-TKA) and the effects on clinical outcomes. Methods: A retrospective analysis was performed on 227 patients diagnosed with knee osteoarthritis, 105 males and 122 females, with the age of (68.6±7.2) years (range: 52 to 86 years). The patients underwent unilateral TKA at the Department of Orthopaedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January 2020 to July 2021. The patients were divided into the KA-TKA group (n=102) and the MA-TKA group (n=125) according to the alignment method. The Blackburne-Peel index, lateral patellofemoral angle, patellofemoral tilt angle and patellofemoral index of the two groups were recorded before and 6 months after operation. The frequency of lateral patellar retinaculum release, preoperative and postoperative knee range of motion (ROM), and Oxford knee score(OKS) were also recorded. The differences between preoperative and postoperative measurement data of each group were calculated. If the difference was in line with normal distribution, the independent sample t-test or t'-test was used for comparison between the two groups. If it did not conform to normal distribution, Mann-Whitney U test was used. Paired sample t-test was used for comparison before and after treatment. Chi-square test was used for comparation of categorical data between the two groups. Results: After 6 months of operation, the patellar tilt angles of the KA-TKA group and the MA-TKA group were (14.22±3.26)° and (13.35±2.27)°, and the lateral patellar angles were (9.73±4.86)° and (11.91±3.89)°, respectively. The change of lateral patellofemoral angle in the KA-TKA group was significantly less than that in the MA-TKA group ((1.68±4.86)° vs. (4.15±4.88)°, t=3.805, P<0.01). OKS and ROM were improved in the both groups at 6 months after operation (all P<0.05), but there were no statistic significance in preoperative and postoperative difference between the two groups (all P>0.05). The intraoperative lateral patellar retinacular release rate was 14.4% (18/125) in the MA-TKA group and 6.9% (7/102) in the KA-TKA group, with no statistical difference (χ2=3.256,P=0.071). Conclusions: There are greater patella lateral tilt at 6 months postoperatively in the KA-TKA group compared with the MA-TKA group, but this radiographic difference could not show differences of clinical outcomes and postoperative ROM, the frequency of intraoperative lateral patellar retinacular release wouldn't increase. Therefore, KA-TKA does not increase the difficulty of postoperative patellofemoral joint complications and intraoperative lateral patellar release.

[Trueness of 4 three-dimensional facial scanners: an in vitro study].

Objective: To investigate the trueness of 4 three-dimensional (3D) facial scanners and to evaluate the applicability of their clinical use. Methods: An art head model was used as the scanning object, and it was scanned by Handyscan 3D scanner in an enclosed environment with a fixed light source to obtain the reference digital model. Three fixed 3D facial scanners (A: 3dMDface; B: Facego Pro; C: RDS Facescan) and a portable hand-held 3D facial scanner (D: Revopoint POP 2) were used to scan the art head model 10 times, and 10 models of each scan group were obtained. The face of the reference model was divided into 16 regions according to anatomy and muscle distributions in the Geomagic Wrap software with saved boundary curves of whole face and each region. The test models were also divided into 16 regions through the curves above after registered with the reference model through "Best fit" function. The root-mean-square error (RMS) of the complete test models and their segmented regions compared with the reference model and its corresponding regions were calculated by 3D comparison function. The smaller the RMS, the higher the accuracy. One-way ANOVA and SNK post-test were used for statistical analysis. Results: RMS of complete test models scanned by A, B, C, D scanners were (0.295±0.005), (0.216±0.053), (0.059±0.012) and (0.103±0.026) mm (F=123.81, P<0.001), respectively. There was significant difference between any two groups (P<0.05). For each facial region, the group D had the best trueness in nasal region, lip region, left orbital region and right orbital region [RMS were (0.079±0.032), (0.061±0.019), (0.058±0.021), (0.081±0.032) mm, respectively], while the group C had the best trueness in frontal region, left buccal region, right buccal region, left zygomatic region, right zygomatic region, left parotideomasseteric region, right parotideomasseteric region, left temporofacial region, right temporofacial region, mental region, left infraorbital region and right infraorbital region [RMS were (0.039±0.011), (0.034±0.007), (0.033±0.007), (0.066±0.023), (0.038±0.022), (0.070±0.030), (0.067±0.024), (0.063±0.029), (0.045±0.023), (0.063±0.006), (0.039±0.010), (0.046±0.008) mm, respectively]. Conclusions: On the basis of art head model scanning, although the overall average deviation between the scanning model and the reference models obtained by the four kinds of 3D facial scanners were small, the portable handheld 3D facial scanner (D) has better accuracy than the fixed 3D facial scanners (A, B, C) in the orbital area, nasal area, lip area and areas with rich features.

[The opportunities and challenges of gynecologic cancer in precision medicine].

In recent years, the diagnosis and treatment of gynecologic cancer have entered a new era with the development of precision medicine. The diagnosis and treatment modes for ovarian cancer, cervical cancer, and endometrial cancer are constantly adjusted. The application of molecular targeted drugs and the progress of surgical concepts and technology have greatly improved the survival of patients with ovarian cancer. Immunotherapy and targeted therapy have become a new hot spot in the treatment of cervical cancer. More clinical research data have been accumulated on the comparison of laparoscopic and open radical hysterectomy in cervical cancer. The surgical management of endometrial cancer has been improved, and molecular diagnostics are increasingly used to guide the diagnosis and treatment of endometrial cancer. Meanwhile, it's necessary to realize the limitations and challenges of precision medicine in gynecologic cancer.

[ALK-positive large B-cell lymphoma with EBV infection or cyclin D1 expression: a clinicopathological analysis of 3 cases].

Objective: To investigate the clinicopathological features and misdiagnosis factors of ALK positive large B-cell lymphoma (ALK+LBCL). Methods: The clinicopathological data of 3 patients with ALK+LBCL in the Department of Pathology, the Affiliated Hospital of Xuzhou Medical University from 2010 to 2021 were collected retrospectively. Immunohistochemistry (IHC) was used for immunophenotyping, in-situ hybridization (ISH) for EBV-encoded RNA (EBER) detection, in-situ fluorescence hybridization (FISH, break-apart probes) for ALK, MYC, and CCND1 translocations. Next-generation sequencing (NGS) was used for the detection of gene fusions and mutations. And clinicopathological features and prognosis of patients were analyzed. Results: Among the 3 ALK+LBCL patients, there were 2 males and 1 female, aged 42, 59, and 39 years, respectively, none of which presented with B symptoms. Case 1 showed systemic lymphadenopathy with elevated serum EBV DNA loading, while cases 2 and 3 presented with extranodal lesions in the nasal and hard palate, respectively. Bone marrow biopsies were performed in cases 1 and 3, and neither showed involvement. Case 1 was at clinical stage Ⅲ while both cases 2 and 3 were at stage Ⅰ, and IPI score ranged 0-1 in all cases. The morphology of these cases was similar. The architecture was effaced by sheets of cohesive large cells growing in extensive infiltration and intra-sinus growth pattern. The neoplastic cells showed immunoblastic or plasmablastic morphology, and large anaplastic cells were easily found. The tumor cells expressed ALK protein cytoplasmically in almost all cells, with ALK gene translocations detected by FISH. Common B-cell and T-cell markers, including CD20, PAX5, CD19, CD2, CD3, CD5, CD7, CD43, CD56, and bcl-2, were negative, while plasmacytic differentiation markers, including CD138, CD38, and MUM1, were positive; CD22, BOB1 and OCT2 were variably expressed. CD10 was strongly expressed only in case 3. All cases were negative for bcl-6 but positive for CD4, perforin, CD30 (partial cells), pSTAT3 (diffusely), and MYC (40%-50%). The Ki-67 index was ranged 60%-70%. MYC translocation was not detected in any case by FISH. In case 1, EBER was strongly positive in>90% of tumor cells. Case 3 was diffusely positive for cyclin D1 but negative for SOX11 expression and CCND1 translocation. All cases harbored ALK fusion genes detected by NGS. In case 1, the fusion partner was TFG, which had not been reported in DLBCL, while in the other 2 cases, ALK fused with the CTCL gene, which was commonly seen in ALK+LBCL. Cases 1 and 3 were treated with ECHOP-based chemotherapy for six cycles and were followed up for 70 and 27 months, respectively, and both achieved complete remission. Conclusions: ALK+LBCL cases with diffuse EBER-positivity reported in this study show TGF as a new fusion partner of ALK in DLBCL, together with cyclin D1 expression. These rare cases are easily confused with EBV positive diffuse large B-cell lymphoma, not otherwise specified (EBV+DLBCL, NOS), cyclin D1 positive diffuse large B-cell lymphoma (cyclin D1+DLBCL) and ALK positive anaplastic large cell lymphoma (ALK+ALCL), resulting in misdiagnosis. Being aware of these rare phenotypes is essential for pathologists to diagnose ALK+LBCL and guide appropriate treatment accurately.

[The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome].

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.

[The IL-6/STAT3 signaling pathway mediated by radiotherapy regulates the expression of PD-L1 in esophageal cancer cells].

Objective: To explore the possible mechanism of radiotherapy regulating the expression of PD-L1 in esophageal carcinoma. Methods: Three esophageal cancer cell lines (Eca109, Kyse150, TE1) were irradiated with different doses of X-rays, and 6 Gy+ AG490 group was set. The mRNA expression of PD-L1 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein expressions of PD-L1, STAT3, p-STAT3 were detected by western blotting and the protein level of IL-6 was detected by ELISA. Results: The mRNA expressions of PD-L1 in Eca109, Kyse150 and TE1 were 2.86±0.30, 960.01±21.27 and 106.78±6.67, higher than 1.07±0.15 in normal esophageal cell line HET-1A (P<0.01). The protein expressions of PD-L1 in Eca109, Kyse150 and TE1 were 0.091±0.036, 1.533±0.079 and 0.914±0.035, higher than 0.063±0.01 in normal esophageal cell line HET-1A (P<0.01). After 48 hours of 6 Gy irradiation, the protein expression levels of PD-L1 in Eca109, Kyse150 and TE1 were 0.135±0.007, 1.66±0.06 and 1.32±0.06, higher than 0.09±0.01, 1.21±0.05 and 0.93±0.03 of the 0 Gy group (P<0.01), while the protein expression levels of p-STAT3 in Eca109, Kyse150 and TE1 were 1.44±0.26, 0.75±0.04 and 1.92±0.17, higher than 0.18±0.05, 0.48±0.02 and 0.36±0.06 of the 0 Gy group (P<0.01). IL-6 protein expression increased significantly after different doses of irradiation (P<0.01). After the IL-6/STAT3 signaling pathway was blocked by the specific inhibitor AG490, the expressions of PD-L1 of Eca109, Kyse150 and TE1 in the 6 Gy+ AG490 groups were 0.11±0.03, 1.07±0.08 and 0.96±0.11, without significant differences of 0.09±0.01, 0.96±0.05 and 0.85±0.09 of the 0 Gy group (P>0.05), while the protein expressions of p-STAT3 were 0.76±0.11, 0.59±0.06 and 0.96±0.12, without significant differences of 0.67±0.08, 0.54±0.06 and 0.84±0.11 of the 0 Gy group (P>0.05). Conclusion: Radiotherapy may regulate the expression of PD-L1 in esophageal cancer cells through IL-6 / STAT3 signaling pathway.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.