A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

A new pyrazine from Hypecoum erectum L / 药学学报

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Prognostic Significance of Intratumoral and Peritumoral Budding in Distal Extrahepatic Bile Duct Carcinoma.

INTRODUCTION: Although tumor budding (TB) has been recognized as a representative adverse prognosticator in gastrointestinal malignancies, it is not well-elucidated in distal extrahepatic bile duct carcinoma (DBDC). Herein, we investigated the prognostic significance of peritumoral (PTB) and intratumoral (ITB) budding according to the modified DBDC staging of the 8th edition of the American Joint Committee on Cancer. METHODS: PTB and ITB were independently evaluated in a cohort of DBDC patients (n = 410) based on the 2016 International Tumor Budding Consensus Conference (ITBCC). RESULTS: High levels of PTB (PTBHigh, ≥ grade-2) and ITB (ITBHigh, ≥ grade-3) were identified in 316 (77%) and 238 (58%) cases, respectively. In univariate analysis, PTBHigh and ITBHigh, larger size and sclerosing tumor growth pattern, higher histologic grade, extrapancreatic location, adenocarcinomas unrelated to intraductal papillary neoplasm of the bile duct (IPNB), pancreatic, duodenal, and lymphovascular invasion, perineural invasion, cancer involvement of the bile duct resection margin, nodal metastasis, and higher T and N categories and disease stages were associated with shorter patient overall survival (OS) times. In multivariate analysis, PTBHigh and ITBHigh remained poor independent prognostic indicators of OS in DBDC patients. Specifically, ITBHigh could predict poor prognosis in patients with stage I (T1N0) DBDC. CONCLUSIONS: Both PTBHigh and ITBHigh were strong prognostic indicators in patients with DBDC. Thus, ITB could be used to predict worse prognoses in patients with DBDC, in which PTB is difficult to assess, especially for patients with stage I (T1N0) DBDC.

The influence of home isolation during COVID-19 on the physical fitness development of college students: a study utilizing repeated measures analysis of variance.

BACKGROUND: Research on the impact of COVID-19-induced home isolation on the physical fitness of college students is limited. This study aims to compare and analyze the physical fitness test scores of college students in two groups: those who experienced home isolation and those who did not, over three consecutive years after enrolment, to investigate the effects of home isolation on the physical fitness development of Chinese college students. METHODS: This comparative study included two longitudinal surveys conducted among medical college students. The participants were divided into an experimental group and a control group. The physical fitness indicators measured included body mass index (BMI), vital capacity (VC), 50-metre run, sit-and-reach, standing long jump, 1000/800-metre runs (males/females), pull-ups (males) and sit-ups (females). Repeated measures analysis of variance (ANOVA) was employed, and the Greenhouse-Geisser correction was applied when Mauchly's assumption of sphericity was violated. Pairwise comparisons were conducted using the Bonferroni method. RESULTS: A total of 6580 students participated in the study, with 3360 students (1490 males, 1870 females) enrolled in 2019 as the experimental group and 3220 students (1326 males, 1894 females) enrolled in 2017 as the control group. All participants completed the physical fitness tests for three consecutive years. The results showed that the experimental group exhibited decreased performance in the 1000-metre and 800-metre runs, and improved performance in the sit-and-reach test. After the end of home isolation, there was an improvement in the performance of the 1000-metre run and 800-metre run, while no significant differences were observed in the trends of the other tested indicators. CONCLUSION: The findings of this study indicate that the home isolation environment during COVID-19 had a significant impact on the physical fitness of college students, specifically in terms of endurance and flexibility qualities, as well as male BMI. To better prepare for future public health emergencies and mitigate the effects of isolation, teaching students endurance exercises that can be performed at home should be prioritized. Furthermore, physical education programs should be improved to enhance student flexibility.

Magnitude and Duration of Serum Neutralizing Antibody Titers Induced by a Third mRNA COVID-19 Vaccination against Omicron BA.1 in Older Individuals.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) is dominating coronavirus disease 2019 (COVID-19) worldwide. The waning protective effect of available vaccines against the Omicron variant is a critical public health issue. This study aimed to assess the impact of the third COVID-19 vaccination on immunity against the SARS-CoV-2 Omicron BA.1 strain in older individuals. MATERIALS AND METHODS: Adults aged ≥60 years who had completed two doses of the homologous COVID-19 vaccine with either BNT162b2 (Pfizer/BioNTech, New York, NY, USA, BNT) or ChAdOx1 nCoV (SK bioscience, Andong-si, Gyeongsangbuk-do, Korea, ChAd) were registered to receive the third vaccination. Participants chose either BNT or mRNA-1273 (Moderna, Norwood, MA, USA, m1273) mRNA vaccine for the third dose and were categorized into four groups: ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273. Four serum specimens were obtained from each participant at 0, 4, 12, and 24 weeks after the third dose (V1, V2, V3, and V4, respectively). Serum-neutralizing antibody (NAb) activity against BetaCoV/Korea/KCDC03/2020 (NCCP43326, ancestral strain) and B.1.1.529 (NCCP43411, Omicron BA.1 variant) was measured using plaque reduction neutralization tests. A 50% neutralizing dilution (ND50) >10 was considered indicative of protective NAb titers. RESULTS: In total, 186 participants were enrolled between November 24, 2021, and June 30, 2022. The respective groups received the third dose at a median (interquartile range [IQR]) of 132 (125 - 191), 123 (122 - 126), 186 (166 - 193), and 182 (175 - 198) days after the second dose. Overall, ND50 was lower at V1 against Omicron BA.1 than against the ancestral strain. NAb titers against the ancestral strain and Omicron BA.1 variant at V2 were increased at least 30-fold (median [IQR], 1235.35 [1021.45 - 2374.65)] and 129.8 [65.3 - 250.7], respectively). ND50 titers against the ancestral strain and Omicron variant did not differ significantly among the four groups (P = 0.57). NAb titers were significantly lower against the Omicron variant than against the ancestral strain at V3 (median [IQR], 36.4 (17.55 - 75.09) vs. 325.9 [276.07 - 686.97]; P = 0.012). NAb titers against Omicron at V4 were 16 times lower than that at V3. Most sera exhibited a protective level (ND50 >10) at V4 (75.0% [24/32], 73.0% [27/37], 73.3% [22/30], and 70.6% [12/17] in the ChAd/ChAd/BNT, ChAd/ChAd/m1273, BNT/BNT/BNT, and BNT/BNT/m1273 groups, respectively), with no significant differences among groups (P = 0.99). CONCLUSION: A third COVID-19 mRNA vaccine dose restored waning NAb titers against Omicron BA.1. Our findings support a third-dose vaccination program to prevent the waning of humoral immunity to SARS-CoV-2.

Prognostic Significance of Cyclin D1 Expression in Small Intestinal Adenocarcinoma.

Cyclin D1, a critical cyclin-dependent kinase (CDK) 4/6-dependent regulator of G1/S transition, has attracted much interest as a therapeutic target. The cyclin D1 expression in small intestinal adenocarcinomas (SIACs) has not yet been comprehensively studied, owing to the rarity of this tumor. We investigated the clinicopathological and prognostic significance of the cyclin D1 expression in 232 surgically resected primary SIACs through a multi-institutional study. A high expression of cyclin D1 (cyclin D1High) was detected in 145 SIAC cases (63%), which was significantly higher than that in normal small intestinal mucosa (11%). Cyclin D1High was more commonly found in SIACs with a lower T-category and disease stage and KRAS mutation and predicted better patient survival. Multivariate analysis revealed that cyclin D1High, the absence of retroperitoneal seeding and lymphovascular invasion, and the lower N-category were identified as independent prognostic indicators for patients with SIACs. Specifically, cyclin D1High affected patient survival in the lower stage group (stages I and II). In conclusion, cyclin D1 was commonly overexpressed in SIACs, and cyclin D1High acted as a favorable prognostic indicator in patients with SIACs. These findings in SIACs may, thus, be important to further comprehend the mechanism of cyclin D1 in carcinogenesis and to strategize appropriate patient therapies.

Comparison of three fixation methods in paediatric metaphyseal-diaphysis junction fracture of the distal radius: a retrospective study in two centres.

Background: The distal radial metaphyseal-diaphysis junction fractures (DRMDJ) have various treatment methods and are easily lead to complications. This study aims to compare the anterograde elastic stable intramedullary nailing (ESIN-A), retrograde K-wire fixation (KW-R), and retrograde precision-shaping elastic intramedullary nailing (ESIN-RPS) for the treatment of pediatric DRMDJ fractures. Materials and methods: A total of 113 patients with DRMDJ fractures (36 in the ESIN-A group, 52 in the KW-R group, and 25 in the ESIN-RPS group) from two centres were retrospectively analysed. Perioperative operation time, intraoperative bleeding, fluoroscopy times, alignment rate and angulation on radiography were compared among the three groups. Forearm rotation, healing, wrist function, and complications were compared at the last follow-up. Results: The mean operation times of the three groups were as follows: KW-R (72 ± 13 min) > ESIN-A (65 ± 18 min) > ESIN-RPS (52 ± 11 min), with a significant difference (P < 0.01). The incision length and intraoperative blood loss of ESIN-A (1.8 ± 0.2 cm; 8.3 ± 3.7 ml) were significantly higher than ESIN-RPS (1.4 ± 0.8 cm; 5.5 ± 2.7 ml) (P < 0.05), respectively. The postoperative alignment rate on the anteroposterior (AP) and the lateral plane of ESIN-RPS (93.1 ± 4.4%; 95.01 ± 2.8%) was significantly greater than that of KW-R (82.1 ± 6.8%; 88.5 ± 4.5%) and ESIN-A (79.2 ± 5.2%; 83.2 ± 2.5%) (P < 0.01). The residual angulation of ESIN-RPS (3.3 ± 1.2°; 2.9 ± 0.8°) was significantly greater than that for ESIN-A (5.1 ± 1.7°; 4.9 ± 2.1°) and KW-R (6.6 ± 2.8°; 7.5 ± 1.6°) (P < 0.05). The excellent and good ratio of ESIN-RPS (95.8%) was significantly higher than that of ESIN-A (86.5%) and KW-R (86.1%) according to the Gartland-Werley standard. There was a significant difference in delayed union between the KW-R and ESIN-A (P < 0.05). Additionally, there were two cases of radial nerve injury in the ESIN-A group, one case of tendon rupture in the ESIN-RPS group, and one case of tendon rupture in the KW-R group. The ESIN-RPS group had significantly fewer complications than the KW-R group (P < 0.05). The ESIN-A group also had significantly fewer complications than the KW-R group (P < 0.05). Conclusion: Compared with ESIN-A and KW-R, ESIN-RPS has the advantages of a shorter operation time, less intraoperative blood loss, less radiation, better alignment, and fewer complications. The ESIN-RPS was suggested as an optimal choice for paediatric DRMDJ fractures.

Qizhi Jiangtang capsule activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.

OBJECTIVE: To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule (, QZJT) on diabetic kidney disease (DKD) treatment. METHODS: This experiment used db/db mice and podocytes (MPC5) to develop DKD model. Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters (24-h urinary albumin, serum creatinine, blood urine nitrogen), pathological kidney injury, and podocyte integrity. Moreover, autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy. Additionally, Western blotting was applied to detect the expression of podocyte marker protein (podocin), autophagy-associated proteins, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway changes and . RESULTS: QZJT significantly reduced urine protein, blood nitrogen urea, and serum creatinine and showed histological restoration of renal tissues. QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice. QZJT increased autophagic vesicles in mice and cultured podocytes. QZJT also upregulated microtubule-associated protein 1 light chain 3-II (LC3-II) / (LC3-I) and Beclin-1 and downregulated phosphorylated-PI3K (p-PI3K), p-AKT, and p-mTOR in db/db mice and MPC5 cells. However, autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells. CONCLUSIONS: These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.

A Case of Human Mpox with Isolated Perianal Ulcers Development in Convalescent Phase.

A 35-year-old man who returned from Germany developed fever, generalized pain, severe anal pain, and generalized skin rash, confirmed to be monkeypox (mpox). While he was previously confirmed to be human immunodeficiency virus infected, antiretroviral therapy ensured his immunocompetence. The mpox-related prodromal symptoms disappeared before isolation, and subsequent several vesicular skin lesions healed after admission. While moderate anal pain persisted for a few days, it improved during hospitalization. The mpox virus was no longer detected in samples taken from the upper respiratory tract and skin by polymerase chain reaction upon admission. However, isolated perianal ulcers developed after admission without any other mpox-related symptoms or signs, and a viable mpox virus was isolated from these ulcers. Considering the novel feature of asynchronous mucocutaneous lesion development in the current mpox epidemic, meticulous physical examination of newly developing lesions, especially in anogenital areas, should be performed during mpox management.

Prognostic Potential of Cyclin D1 Expression in Colorectal Cancer.

Cyclin D1 is mainly known as an oncogenic driver in cancers, and the dysregulated cyclin D1/cyclin-dependent kinase (CDK) 4/6 axis is considered an attractive target for cancer therapy. Recent studies have reported that tumors respond to therapeutic interventions targeting altered cyclin D1 expression via application of the CDK4/6 inhibitor. However, the prognostic and therapeutic contributions of cyclin D1 to colorectal cancer (CRC) remain controversial. Herein, we assessed the associations between cyclin D1 expression and clinicopathological factors, including patients' overall survival (OS) and recurrence-free survival (RFS), in 495 surgically resected primary CRCs. We also examined previous studies for cyclin D1 in CRCs. High expressions of cyclin D1 (cyclin D1High) was observed in 389 CRC cases (78.6%). Cyclin D1High consistently predicted better patient OS and RFS in CRCs. Based on multivariate analysis, cyclin D1High and young age of patients remained as independent prognosticators of higher OS rate, whereas cyclin D1High, females, chemotherapy, absence of nodal metastasis, and lower T-category remained as independent prognosticators of better RFS. Cyclin D1 is commonly overexpressed in CRCs, and its expression can be used as a favorable prognostic indicator in patients with CRCs; this may be important for predicting responses to subsequent CDK4/6 inhibitors.

Tumor Microenvironment Prognostic Risk and Its Association With MUC5AC in Ampullary Carcinoma.

CONTEXT.­: The tumor-host interaction in the tumor microenvironment (TME) affects the prognosis of patients with malignant tumors. TME assessed via tumor budding (BD) and tumor-infiltrating lymphocyte (TIL) had a prognostic impact in patients with nonampullary small intestinal and colorectal carcinomas. In ampullary carcinoma (AC), MUC5AC was recently revealed as a significant prognosticator, but studies about the TME have not been conducted. OBJECTIVE.­: To assess TME-based prognostic risk in AC. DESIGN.­: We generated a collective TME risk index based on high-grade BD at the invasive front (BD3) and high density of stromal-TIL (>5%) in 64 surgically resected ACs. We evaluated its predictive values for overall survival (OS) and recurrence-free survival (RFS). We also investigated the relationship of TME to MUC5AC expression. RESULTS.­: TME prognostic risk index was classified into low-risk (BDLow/TILHigh; 26 of 64; 41%), intermediate-risk (BDLow/TILLow or BDHigh/TILHigh; 23; 36%), and high-risk (BDHigh/TILLow; 15; 23%) groups. Higher TME prognostic risk was associated with higher tumor grade (P = .03), lymphovascular invasion (P = .05), and MUC5AC immunopositivity (P = .02). TME prognostic risk index displayed better predictive ability for both OS (53.9 versus 46.1 versus 42.2) and RFS (24.8 versus 16.9 versus 15.3) than BD or TIL alone. In multivariate analysis, TME prognostic risk index was an independent prognosticator for OS (P = .003) and RFS (P = .03). CONCLUSIONS.­: TME risk index in combination with BD and TIL was a stronger predictor of prognostic risk stratification than either BD or TIL alone for both OS and RFS in patients with AC. MUC5AC may modulate the interaction between tumor cells and immunity toward enhancing invasiveness in TME.

Efficacy of alcohol septal ablation in mildly symptomatic or severely symptomatic patients with hypertrophic obstructive cardiomyopathy / 中华心血管病杂志

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.

Comparative study on radiological features between serum aquaporin 4 antibody positive and negative neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the clinical and imaging differences between serum aquaporin 4 (AQP4) antibody positive and negative patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data and radiologic findings of 89 NMOSD patients diagnosed at Beijing Tiantan Hospital, Capital Medical University from January 2018 to June 2022 were retrospectively analyzed. There were 17 male cases and 72 female cases, aged 18-74 years. According to the results of serum AQP4 antibody test, the patients were divided into AQP4 antibody positive group and AQP4 antibody negative group, and the differences in clinical data, lesion distribution, lesion characteristics, and brain area volume between the 2 groups were compared using independent sample t-test and χ 2 test, and the correlation between brain area volume and expanded disability status scale (EDSS) scores was further investigated using Spearman correlation analysis. Results:There were 68 cases in the AQP4 antibody positive group and 21 cases in the AQP4 antibody negative group. Patients in both groups were predominantly female, but the percentage of females in the AQP4 antibody-positive group (86.8%, 59/68) was higher than that in the AQP4 antibody-negative group (61.9%, 13/21), with a statistically significant difference (χ 2=4.91, P=0.027). The incidence of optic neuritis in AQP4 antibody negative group (66.7%, 14/21) was higher than that in antibody positive group (41.2%, 28/68), with a statistically significant difference (χ 2=4.18, P=0.041). In the distribution of intracranial lesions on MRI, the probability of lesions involving the brain stem in AQP4 antibody negative group (47.6%, 10/21) was higher than that in AQP4 antibody positive group (23.5%, 16/68), the difference had statistically significance (χ 2=4.50, P=0.034). The volumes of whole brain white matter, right amygdala, right accumbens-area and right ventral diencephalon in AQP4 antibody positive group were lower than those in AQP4 antibody negative group ( P<0.05), and the volumes of the right accumbens-area were negatively correlated with the EDSS scores in AQP4 antibody positive group ( r=-0.628, P=0.009). Conclusion:There are differences in clinical and imaging manifestations between AQP4 antibody positive and AQP4 antibody negative patients, which provides more basis for clinical in-depth understanding of NMOSD.

Comparison of three surgical fixation methods for fracture of distal radial metaphyseal diaphyseal junction in children / 中华创伤骨科杂志

Objective:To compare the effects of anterograde elastic stable intramedullary nailing (ESIN-A), retrograde K-wires fixation (KW-R) and retrograde precision shaping of elastic stable intramedullary nailing (ESIN-RPS) in the treatment of fractures of distal radial metaphyseal diaphyseal junction (DRMDJ) in children.Methods:A retrospective study was conducted to analyze the data of 112 eligible children with DRMDJ fracture who had been treated at Department of Orthopedics, Children's Hospital, Anhui Medical University and Department of Orthopedics, The People's Hospital of Fuyang City,Anhui Medical University, from January 2016 to May 2022. There were 64 males and 48 females, with an age of (8.4±2.3) years. The children were divided into 3 groups according to different surgical fixation methods: group ESIN-A of 36 cases, group KW-R of 52 cases, and group ESIN-RPS of 24 cases. The operation time, intraoperative bleeding, fluoroscopy times, alignment rates and residual angulations by the anteroposterior and lateral X-ray films immediately after reduction were compared among the 3 groups. The Gartland-Werley evaluation of wrist function and complications were compared at the last follow-up.Results:There was no statistically significant difference in the preoperative general data among the 3 groups, indicating comparability ( P>0.05). In the operation time, group KW-R [(71.2±9.2) min] > group ESIN-A [(65.1±13.1) min] > group ESIN-RPS [(51.7±17.1) min]; in the fluoroscopy times, group KW-R [(13.9±6.3) times] > group ESIN-A [(9.0±2.8) times] > group ESIN-RPS [(6.4±2.0) times]; in the alignment rates by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (93.1%±4.6% and 95.2%±3.3%) > group KW-R (82.1%±11.0% and 88.1%±7.4%) > group ESIN-A (80.4%±9.9% and 86.7%±6.9%); in the residual angulations by the anteroposterior and lateral X-ray films immediately after reduction, group ESIN-RPS (3.3°±1.8° and 2.9°±2.1°) < group ESIN-A (5.2°±1.0° and 5.0°±3.2°) < group KW-R (6.6°±1.6°and 7.5°±2.7°). Pairwise comparisons in the above items were statistically significant ( P<0.05). In group ESIN-A, the incision length [(1.8±0.3) cm] was significantlylonger than that in group ESIN-RPS [(1.4±0.2) cm], and the intraoperative blood loss [(8.3±2.2) mL] significantly larger than that in group ESIN-RPS [(5.5±1.6) mL] ( P<0.05). One year after operation, the excellent and good rate by the Gartland-Werley evaluation of wrist function in groups ESIN-RPS, ESIN-A and KW-R, respectively, were 95.8% (23/24), 86.5% (31/36) and 86.1% (46/52), showing no statistically significant difference between the 3 group ( P>0.05), and the major incidence of complications in group KW-R (25.0%, 13/52) and in group ESIN-A (25.0%, 9/36) were significantly higher than that in group ESIN-RPS (4.2%, 1/24) ( P<0.05). Conclusion:In the treatment of DRMDJ fractures in children, compared with ESIN-A and KW-R, ESIN-RPS is an effective choice due to its advantages of shorter operation time, less intraoperative blood loss, less radiation, better alignment, and fewer complications.

Risk factors for failure in closed reduction of flexed supracondylar humerus fractures in children / 中华创伤骨科杂志

Objective:To identify the risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children.Methods:The data of 171 children were retrospectively analyzed who had been treated for flexed supracondylar humerus fractures of Wilkins type Ⅲ from January 2013 to December 2021 at Department of Orthopaedics, Children's Hospital of Jiangxi Province and Children's Hospital of Fudan University Anhui Hospital. They were divided into a reduction failure group (35 cases) and a reduction success group (136 cases). Factors such as fracture height, age, body mass index, ulnar-radial offset direction, obvious axial rotation of the distal fracture fragment, combined ulnar nerve injury, and time from injury to operation were listed as risk factors. The independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures were identified by univariate analysis of variance and multi-variate logistic regression analysis.Results:The average age of 171 children was (7.8±2.6) years. There were 151 cases of radial deviation and 20 cases of ulnar deviation, 120 high type fractures and 51 low type fractures, and 20 cases of combined ulnar nerve injury and 115 cases of obvious rotation of the distal fracture fragment. The one-way ANOVA showed statistically significant differences between the reduction failure group and the reduction success group in terms of age, obvious rotation of the distal fracture fragment, and ulnar nerve injury ( P<0.05), but no significant differences in fracture height, body mass index, ulnar-radial offset direction, or time from injury to operation ( P>0.05). Multivariate logistic regression analysis showed that obvious rotation of the distal fracture fragment ( OR=3.287, 95% CI: 1.136 to 9.513, P=0.028) and combined ulnar nerve injury ( OR=6.439, 95% CI: 2.262 to 18.327, P=0.001) were risk factors for failure in closed reduction. Conclusion:As obvious rotation of the distal fracture fragment and combined ulnar nerve injury may be independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children, they should arouse more attention in the treatment of such fractures.

A technique of "de-sharpening" intramedullary elastic reduction with Kirschner wire for the treatment of Gartland type III posterolaterally-displaced supracondylar humerus fracture in children / 中华创伤杂志

Objective:To compare the clinical effect of "de-sharpening" intramedullary elastic reduction with Kirschner wire and traditional three-dimensional manipulation for the treatment of Gartland type III posterolaterally-displaced supracondylar humerus fracture in children.Methods:A retrospective cohort analysis was made on 106 children with Gartland type III posterolaterally-displaced supracondylar humerus fracture treated in Anhui Provincial Children′s Hospital from March 2020 to June 2022, including 58 males and 48 females; aged 1-12 years [(8.7±2.3)years]. The patients were assigned to "de-sharpening" intramedullary elastic reduction with Kirschner wire (study group, n=50) and traditional three-dimensional manipulation (control group, n=56). The operation time, frequency of intraoperative fluoroscopy, fracture healing time, difference of Baumann angle between the normal and injured side at postoperative 3 and 6 months, elbow function Flynn score at last follow-up and complications were compared between the two groups. Results:All children were followed up for 6-12 months [(8.5±1.2)months]. The operation time and frequency of intraoperative fluoroscopy were (32.9±3.7)minutes and (20.6±5.4)times in study group, significantly different from (45.6±10.1)minutes and (32.5±8.2)times in control group (all P<0.05). The fracture healing time was (33.0±5.1)days in study group, similar with (33.8±4.7)days in control group ( P>0.05). At 3 and 6 months after operation, the difference of Baumann angle between the normal and injured side was (3.2±0.8)°and (2.3±0.6)°in study group compared to (6.0±2.1)°and (5.8±1.3)°in control group (all P<0.01). According to the elbow function Flynn score at the last follow-up, the results were excellent in 44 children, good in 5 and fair in 1, with the excellent and good rate of 98.0% (49/50) in study group, and were excellent in 47 children, good in 5 and fair in 4, with the excellent and good rate of 92.9% (52/56) in control group ( P>0.05). There were no following complications in both groups, such as osteomyelitis, poor fracture healing, compartment syndrome, iatrogenic neurovascular injury or myositis ossificans. Conclusions:Both "de-sharpening" intramedullary elastic reduction with Kirschner wire and traditional three-dimensional manipulation for the treatment of Gartland type III posterolaterally-displaced supracondylar humerus fracture in children can achieve elbow joint function recovery, with low incidence of complications. However, the former avoids repeated manual reduction, with shorter operation time, less frequency of intraoperative fluoroscopy and better correction of the coronal plane deformity and rotation deformity.

Application of laparoscopic training in the standardized residency training of pediatric general surgery / 中华医学教育探索杂志

Objective:To explore the application of laparoscopic training in the standardized residency training of pediatric general surgery.Methods:A total of 36 rotating residents who received the standardized residency training in the department of pediatric general surgery of Shenzhen Children's Hospital from January 2017 to December 2019 were selected for laparoscopic training. The training content includes the study and training of laparoscopic theory knowledge, laparoscopic surgery video, skills operation of simulated operating system. Assessment was conducted before and after the training, and statistical analysis was performed to compare the difference of scores before and after the training. The self-evaluation of resident's learning efficiency and the satisfaction with teachers were investigated by questionnaires. SPSS 20.0 was used for paired t-test. Results:After receiving the standardized residency training of pediatric general surgery, the theoretical knowledge and cognition of the application on pediatric general laparoscopic surgery were significantly improved among the 36 residents. The time that the skills spent in vitro simulation box during the simulated operation training was significantly reduced after training, with a statistically significant difference ( P < 0.05). According to the questionnaire survey, resident's satisfaction with self-evaluation of learning efficiency was 97.22% (35/36), their satisfaction with teachers was 94.44% (34/36), and their satisfaction with teaching curriculum was 100.00% (36/36). Conclusion:Laparoscopic training can effectively improve the clinical practice ability of pediatric general surgery residents, which is worthy of promotion.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Research on ontology construction of acupuncture effect based on ISO/TS 16843-6: 2022 / 中国针灸

In order to specify the information expression of acupuncture effect and realize the knowledge reuse and sharing, in view of animal experiments and clinical trials, the relevant knowledge of acupuncture effect is allocated. Using seven-step method and Protégé5.5.0 tool, the ontology of acupuncture effect is constructed on the base of ISO/TS 16843-6: 2022. A total of 199 classes are constructed, including 7 categories (acupuncture point, acupuncture therapy, needling method, biological process, genes and gene products, disorder, and anatomic structure), 12 object properties, 1 108 instances and 5 123 axioms. A semantic network with the characteristics of acupuncture and moxibustion is established and the structured expression for the knowledge of acupuncture effects is obtained, which lays the foundation for the innovation and development in the field of acupuncture and moxibustion.

Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1 / 国际口腔科学杂志·英文版

Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.