[Efficacy and safety study of standardized mite allergen specific immunotherapy with no reduction during maintenance in children with respiratory allergic disease].

Objective: To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Method: Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. Results: A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion: Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

The ribotoxic stress response drives UV-mediated cell death.

While ultraviolet (UV) radiation damages DNA, eliciting the DNA damage response (DDR), it also damages RNA, triggering transcriptome-wide ribosomal collisions and eliciting a ribotoxic stress response (RSR). However, the relative contributions, timing, and regulation of these pathways in determining cell fate is unclear. Here we use time-resolved phosphoproteomic, chemical-genetic, single-cell imaging, and biochemical approaches to create a chronological atlas of signaling events activated in cells responding to UV damage. We discover that UV-induced apoptosis is mediated by the RSR kinase ZAK and not through the DDR. We identify two negative-feedback modules that regulate ZAK-mediated apoptosis: (1) GCN2 activation limits ribosomal collisions and attenuates ZAK-mediated RSR and (2) ZAK activity leads to phosphodegron autophosphorylation and its subsequent degradation. These events tune ZAK's activity to collision levels to establish regimes of homeostasis, tolerance, and death, revealing its key role as the cellular sentinel for nucleic acid damage.

Risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta in China: A cross-sectional study.

PURPOSE: To describe the level of risk perception for fractures among family caregivers of children diagnosed with osteogenesis imperfecta, and explore the related factors. DESIGN AND METHODS: This was a cross-sectional survey study. A self-administered questionnaire on family caregivers' perception of fracture risk of underage patients with osteogenesis imperfecta was used. The study was performed in mainland China from May to December 2022, with 127 family caregivers of patients aged 3-17. Stepwise backwards multivariable linear regression analysis was undertaken to examine risk factors for caregivers' risk perception of fractures. RESULTS: A total of 16.54% of caregivers had a higher level of risk perception for fractures of patients. The caregiver's educational level, the family members, the patient's self-care ability, fracture times in the past year, and whether or not they had received community services were associated with the caregiver's risk perception for fracture. CONCLUSIONS: Patients with osteogenesis imperfecta will eventually leave the medical system and receive more support from themselves or family caregivers instead of health personnel. These findings should be incorporated into the prevention and health education of fractures in caregivers of underage patients with osteogenesis imperfecta to help develop effective risk communication strategies and induce caregivers to implement appropriate protective behaviors. PRACTICE IMPLICATIONS: It is important to evaluate the risk perception for fractures and its related factors among family caregivers of underage patients with osteogenesis imperfecta. Identifying these factors can help healthcare providers to screen caregivers with high perceived level of fracture risk in a quicker and earlier way. This study provides evidence for the establishment of interventions to balance caregivers' risk perception and patient socialization.

MRI-based radiomics model to preoperatively predict mesenchymal transition subtype in high-grade serous ovarian cancer.

AIM: To develop a magnetic resonance imaging (MRI)-based radiomics model for the preoperative identification of mesenchymal transition (MT) subtype in high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and eighty-nine patients with histopathologically confirmed HGSOC were enrolled retrospectively. Among the included patients, 55 patients were determined as the MT subtype and the remaining 134 were non-MT subtype. After extracting a total of 204 features from T2-weighted imaging (T2WI) and contrast-enhanced (CE)-T1WI images, the Mann-Whitney U-test, Spearman correlation test, and Boruta algorithm were adopted to select the optimal feature set. Three classifiers, including logistic regression (LR), support vector machine (SVM), and random forest (RF), were trained to develop radiomics models. The performance of established models was evaluated from three aspects: discrimination, calibration, and clinical utility. RESULTS: Seven radiomics features relevant to MT subtypes were selected to build the radiomics models. The model based on the RF algorithm showed the best performance in predicting MT subtype, with areas under the curves (AUCs) of 0.866 (95 % confidence interval [CI]: 0.797-0.936) and 0.852 (95 % CI: 0.736-0.967) in the training and testing cohorts, respectively. The calibration curves, supported with Brier scores, indicated very good consistency between observation and prediction. Decision curve analysis (DCA) showed that the RF-based model could provide more net benefit, which suggested favorable utility in clinical application. CONCLUSION: The RF-based radiomics model provided accurate identification of MT from the non-MT subtype and may help facilitate personalised management of HGSOC.

[The detecting value of virtual non-calcium technique of dual-energy CT for bone marrow edema around nontraumatic osteonecrosis of the femoral head].

Objective: To evaluate the value of virtual non-calcium (VNCa) technique of dual-energy CT (DECT) for detecting bone marrow edema (BME) around nontraumatic osteonecrosis of the femoral head (ONFH) using MRI as reference standard. Methods: Nontraumatic ONFH patients were prospectively studied in the Fourth Medical Center of Chinese PLA General Hospital from October 2022 to May 2023, and their MRI and DECT images were analyzed. The diagnostic efficiency of the subjective assessment of BME around ONFH by two radiologists in VNCa color-coded images were calculated using the MRI results as the reference standard. The BME ranges were compared between VNCa images and MRI. Traditional CT values and VNCa CT values were compared between normal bone marrow and BME. The receiver operator characteristic (ROC) curve was established based on the statistically different CT values, and the area under the curve (AUC) was calculated to find the threshold to distinguish normal bone marrow from BME and evaluate the diagnostic efficacy. Results: Thirty patients with ONFH were included, including 24 males and 6 females, aged (39±12) years. There were 18 bilateral hips and 12 unilateral hips, with a total of 48 hips, 34 hips of which showed BME on MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of subjective detection of BME on VNCa color coded maps by two physicians were 97.1% (33/34) and 97.1% (33/34), 92.9% (13/14) and 71.4% (10/14), 97.1% (33/34) and 89.2% (33/37), 92.9% (13/14) and 90.9% (10/11), 95.8% (46/48) and 89.6% (43/48), respectively, with no statistical difference (all P>0.05).There was no statistical difference between VNCa color-coded images and MRI in the BME range (P=1.160). The traditional CT values measured by the two radiologists were in good agreement with VNCa CT values, with intraclass correlation coefficient (ICC) of 0.948 (95%CI: 0.908-0.971) and 0.982 (95%CI: 0.969-0.990), respectively. The traditional CT value of normal bone marrow was (400.7±82.8) HU, and that of BME was (443.7±65.7) HU, with no statistical difference (P=0.062). The VNCa CT value of normal bone marrow was (-103.1±27.8) HU, and that of BME was (-32.9±25.7) HU, with statistical difference (P<0.001). The AUC of distinguishing normal bone marrow from BME based on VNCa CT value was 0.958 (95%CI: 0.857-0.995). The best cut-off value was -74.5 HU, and when the VNCa CT value was higher than -74.5 HU, the sensitivity, specificity, PPV, NPV and accuracy of diagnosing BME were 97.1%, 92.9%, 97.1%, 92.9% and 95.8 %, respectively. Conclusion: The VNCa technique of DECT has high efficiency in detecting BME around ONFH, and can accurately demonstrate the range of BME.

[Analysis of efficacy and safety of daratumumab-containing regimen in relapsed and refractory multiple myeloma patients].

Objective: To investigate the efficacy and safety in relapsed and refractory multiple myeloma (RRMM) patients with combination regimen of daratumumab. Methods: The clinical data of 42 RRMM patients admitted to Qingdao Municipal Hospital from December 2020 to November 2023 were retrospectively analyzed, which included 26 males and 16 females, with a median age of 59 (47, 82) years old. According to the number of courses of treatment with Daratumumab, patients were divided into three groups: long course group (≥9 courses, n=21), medium course group (7-8 courses, n=12), and short course group (≤6 courses, n=9). The deadline for follow-up was November 10, 2023, and the follow-up period was 15.6 (6.0, 34.0) months. After completing at least 2 courses of treatment, patients were evaluated for efficacy, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), and progressive disease (PD). Basic clinical characteristics of patients, overall response rate of treatment, and adverse reactions were statistically analyzed. Kaplan-Meier method was used to compare the differences of progression-free survival (PFS) in patients with different courses of treatment. Results: Among the 42 patients, 15 (35.7%) had extramedullary disease or plasmacytic leukemia, 7 (16.6%) had amyloidosis, and 18 (42.9%) had renal insufficiency. In Mayo stage, 25 patients (59.5%) were at high risk of myeloma cytogenetic stratification, 8 patients (19%) were standard risk, 9 patients (21.4%) had no cytogenetic data. There were 16 patients with second-line treatment (38.0%), 13 patients with third-line treatment (31%), and 13 patients with more than fourth-line treatment (31%). All patients received at least 2 courses of treatment, achieving the best degree of disease response in 4 cases of sCR (9.5%), 3 cases of CR (7.1%), 10 cases of VGPR (23.8%), 11 cases of PR (26.2%), and 6 cases of MR (14.2%). The overall response rate (ORR) was 80.9% (34/42). The overall response rate was 100% (21/21) in the long course group, 91.6% (11/12) in the medium course group and 22.2% (2/9) in the short course group. Kaplan-Meier survival analysis showed that the duration of PFS was 5.0 (95%CI: 3.1-6.9) months in the short course group,>8.0 months in the medium course group, and>38.0 months in the long course group, the difference was statistically significant (P<0.05). Grade≥3 adverse reactions were mainly neutropenia (3 cases) and thrombocytopenia (1 case). None of the patients discontinued treatment due to adverse reactions. Conclusion: Treatment of RRMM with a regimen containing Daratumumab requires a longer course of treatment to achieve maximum efficacy and the adverse reactions can be controlled.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.

The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear. Here, we show that KIF18A inhibition drives a modest and widespread increase in spindle assembly checkpoint (SAC) signaling from kinetochores which can result in lethal mitotic delays. Whether cells arrest in mitosis depends on the robustness of the metaphase-to-anaphase transition, and cells predisposed with weak basal anaphase-promoting complex/cyclosome (APC/C) activity and/or persistent SAC signaling through metaphase are uniquely sensitive to KIF18A inhibition. KIF18A-dependent cancer cells exhibit hallmarks of this SAC:APC/C imbalance, including a long metaphase-to-anaphase transition, and slow mitosis overall. Together, our data reveal vulnerabilities in the cell division apparatus of cancer cells that can be exploited for therapeutic benefit.

[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].

Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Priority list of potential endocrine-disrupting chemicals in food chemical contaminants: a docking study and in vitro/epidemiological evidence integration.

Diet is an important exposure route of endocrine-disrupting chemicals (EDCs), but many unfiltered potential EDCs remain in food. The in silico prediction of EDCs is a popular method for preliminary screening. Potential EDCs in food were screened using Endocrine Disruptome, an open-source platform for inverse docking, to predict the binding probabilities of 587 food chemical contaminants with 18 human nuclear hormone receptor (NHR) conformations. In total, 25 contaminants were bound to multiple NHRs such as oestrogen receptor α/ß and androgen receptor. These 25 compounds mainly include pesticides and per- and polyfluoroalkyl substances (PFASs). The prediction results were validated with the in vitro data. The structural features and the crucial amino acid residues of the four NHRs were also validated based on previous literature. The findings indicate that the screening has good prediction efficiency. In addition, the epidemic evidence about endocrine interference of PFASs in food on children was further validated through this screening. This study provides preliminary screening results for EDCs in food and a priority list for in vitro and in vivo research.

[Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study].

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

[Research advances on the application of free flaps in repairing diabetic foot ulcers].

Free flaps have been successfully used in the repair of diabetic foot ulcers (DFUs), which can reduce amputation rate, maintain normal gait of patients, and improve life quality of patients. However, there are still many challenges in the repair of DFUs with free flaps, and many problems need to be solved. This paper summarizes the selection of patients, preoperative cautions, types of flaps, methods of vascular anastomosis, clinical effects, and existing problems in using free skin flaps for repairing DFUs.

[Progress in the application of laparoscopic and endoscopic cooperative surgery in gastrointestinal stromal tumors].

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor among gastrointestinal tumors, with an inherent potential for malignancy. The primary approach to addressing GIST remains surgical intervention. Laparoscopic and endoscopic cooperative surgery (LECS) has emerged as an innovative treatment approach for GIST. LECS includes various techniques, such as classic LECS, inverted LECS, and laparoscopic-assisted endoscopic full-thickness resection, all of which aim to combine the advantages of laparoscopy and endoscopy. This treatment offers benefits such as accurate localization, complete lesion removal, and a good prognosis. Generally, LECS can be used for GIST with a tumor diameter less than 50 mm, which cannot be completely removed through traditional endoscopic surgery. The clinical application of LECS deserves further exploration and expansion in the future, ultimately benefiting patients.

[Analysis of disease composition and primary surgical procedures in pediatric secondary glaucoma inpatients: a single-center study].

Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Van der Waals isotope heterostructures for engineering phonon polariton dispersions.

Element isotopes are characterized by distinct atomic masses and nuclear spins, which can significantly influence material properties. Notably, however, isotopes in natural materials are homogenously distributed in space. Here, we propose a method to configure material properties by repositioning isotopes in engineered van der Waals (vdW) isotopic heterostructures. We showcase the properties of hexagonal boron nitride (hBN) isotopic heterostructures in engineering confined photon-lattice waves-hyperbolic phonon polaritons. By varying the composition, stacking order, and thicknesses of h10BN and h11BN building blocks, hyperbolic phonon polaritons can be engineered into a variety of energy-momentum dispersions. These confined and tailored polaritons are promising for various nanophotonic and thermal functionalities. Due to the universality and importance of isotopes, our vdW isotope heterostructuring method can be applied to engineer the properties of a broad range of materials.

[Opportunities and challenges in the diagnosis and treatment of optic chiasm lesions: a clinical and research perspective].

The optic chiasm is a critical component of the visual pathway, and lesions in the pituitary and sellar regions can cause irreversible damage to a patient's visual function, resulting in a significant decrease in their quality of life. As a result, neuro-ophthalmology evaluation is a crucial part of the multidisciplinary treatment of pituitary diseases. However, due to the significant variation in the anatomical structure of the optic chiasm and the sellar region, as well as the complexity of the injury mechanism, chiasm injury can result in diverse manifestations and severity levels, which can make it difficult to correlate with anatomical parameters. In recent years, research has increasingly focused on the early recognition of optic chiasm compression, the prediction of visual function after intervention, and the long-term neurodegenerative effects, while optical coherence tomography (OCT), electrophysiological examinations, and functional magnetic resonance imaging are currently the most commonly used methods for evaluating sellar region lesions. However, the role of these methods, represented by OCT, in clinical diagnosis and treatment, still lacks high-level clinical evidence support, and the evaluation and prediction of optic chiasm function remain key areas for further study. In addition to compression lesions, lesions such as inflammation, infiltration, and demyelination in the sellar region, caused by systemic multi-system diseases, can also lead to visual function damage and require recognition in clinical practice.