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Bingyu Xiu, Zhe Xu, Zigang Xu, Bin Zhang, Li Wei, Lin Ma Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of ChinaCorrespondence: Lin Ma; Li Wei, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Tel +86 10 59616884, Email bch_maleen@aliyun.com; bellewli@sina.comImportance: Port-wine stain (PWS) is a congenital vascular condition involving dilation of skin capillaries and venules, significantly affecting patients’ physical and mental health. Pulsed dye laser (PDL) is widely used for PWS treatment; however, large-scale data on pediatric cases remain limited. This retrospective study aims to investigate the efficacy of laser treatment and its related factors in a large sample.Objective: To assess the clinical efficacy and adverse reactions of 595nm PDL for treating pediatric PWS and to identify factors influencing treatment outcomes.Methods: This retrospective study included 974 pediatric patients with PWS treated at Beijing Children’s Hospital from 2003 to 2021. Inclusion criteria required patients to be under 18, with solitary PWS and Fitzpatrick skin types II–IV. Treatment efficacy was evaluated using standardized photographs taken before and after treatment, with outcomes categorized by Achauer’s clearance criteria. Ridit analysis assessed the impact of variables such as gender, age, lesion location, and treatment frequency on outcomes.Results: The overall efficacy rate was 65.3%, higher in females (69.7%) than males (59.7%). Adolescents had the highest efficacy (100%) due to better compliance. Limb lesions responded best (87.5%), followed by neck (75.0%), trunk (66.7%), and head/face (63.0%). Smaller lesions (≤ 3 cm²) achieved 76.8% efficacy. Efficacy rose with sessions, reaching 84.0% after three. The mandibular branch (V3) had the highest trigeminal efficacy (68.5%). Adverse reactions (4.31%) included pigmentation changes (2.87%), hypopigmentation (1.03%), and minimal scarring (0.41%).Conclusion: The efficacy of 595nm PDL for treating PWS in children is influenced by gender, age, lesion location, size, and the number of treatment sessions. PDL is an effective treatment for pediatric PWS with minimal adverse reactions.Keywords: port-wine stain, 595nm pulsed dye laser, children

Objective To discuss the classification and surgical treatment strategies of complex spinal lipoma in children. Methods A total of 68 children with complex spinal lipoma were selected for treatment at Beijing Tsinghua Changgung Hospital, Affiliated Hospital of Tsinghua University from January 2015 to January 2023. They were divided into dorsal type (n = 42), transitional type (n = 15) and chaotic type (n = 11) based on XIU - SUN classification. All patients underwent microsurgical treatment under neurophysiological monitoring. The early (within one month after surgery) and long-term (over one year after surgery) efficacy and safety of all patients were evaluated. Results Early efficacy: according to the Kirollos grading method for intraoperative decompression, 61 cases (89.71%) reached level Ⅰ , 5 cases (7.35%) reached level Ⅱ , and 2 cases (2.94%) reached level Ⅲ ; according to the degree of resection, complete resection was achieved in 7 cases (10.29%), subtotal resection in 16 cases (23.53%), and partial resection in 45 cases (66.18%). Long-term efficacy: all patients were followed up for (5.00 ± 0.20) years. According to the McCormick spinal cord injury grading system, there was no statistically significant difference in the preoperative and postoperative neurological scores of the dorsal type (χ2 = 0.364, P = 0.549), transitional type (χ2 = 0.125, P = 1.000) and chaotic type (χ2 = 1.500, P = 0.219). MRI examination revealed recurrence of lipoma in 6 cases (8.82%). The postoperative symptoms improved to different degrees, and the progression free survivial rate was 91.18% (62/68). Postoperative complications: 25 cases (36.76%) of postoperative complications were observed, including urinary and fecal dysfunction in 13 cases (19.12%), decreased muscle strength in 9 cases (13.24%), cerebrospinal fluid leakage in 3 cases (4.41%), central nervous system infection leading to acute hydrocephalus in 2 cases (2.94%), with 2 cases presenting with both decreased muscle strength and urinary and fecal dysfunction. Conclusions XIU - SUN classification has a guiding role in surgical strategy. In cases of dorsal type and most of transitional types, a subtotal or complete resection can be chosen. For chaotic type and medullary type, a reduction - based approach is recommended. All types of spinal lipoma should undergo detachment release.

Spinal and spinal cord tumors in children are rare and often present with non-specific symptoms, leading to delayed diagnosis and potentially catastrophic consequences. Most pediatric spinal tumors in children are benign tumors, primarily including osteoid osteomas, osteoblastomas and aneurysmal bone cysts. Malignant spinal tumors are extremely rare, mainly including osteosarcoma, Ewing's sarcoma, lymphoma and metastatic neuroblastoma. Pediatric spinal cord tumors mostly include astrocytomas, ependymomas and schwannomas. There are also congenital benign tumors, such as lipomas and teratomas, which are relatively not uncommon. This article provides a review of the clinical characteristics of spinal and spinal cord tumors in children, with the aim of improving clinical understanding of pediatric spinal and spinal cord tumors, and guiding diagnosis and treatment.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Introduction: Esophageal foreign body impaction is a problem commonly seen in pediatric emergency departments, often requiring emergency surgical removal. However, no cases of foreign body impaction at the ostium of an esophageal diverticulum have been reported in the literature. Case presentation: A 1-year-old boy was admitted to our hospital due to a 5-month history of persisting cough. He was initially diagnosed with an upper respiratory tract infection, which did not respond to medical treatment for 4 months. An X-ray was done at a community hospital, revealing a round-shaped metallic foreign body in the upper esophagus. His parents were unable to recall any unusual history of swallowing foreign objects. Physical examination revealed coarse breath sounds in both lungs, with no other abnormal findings. The patient underwent an initial endoscopy were we found the foreign body, but it was embedded in the esophageal mucosa and could not be retrieved. We subsequently obtained a computerized scan to better understand the location of the foreign body. A second endoscopy was done 48 hours later, during which we were able to remove the foreign body, which was a coin. Once the coin was retrieved, we realized that it had been lodged at the entrance of an esophageal diverticulum. We confirmed the diagnosis 5 days later with a contrast esophagram. The patient recovered successfully without complications. At 6 months of follow up, the patient remains asymptomatic. Conclusion: Persistent cough may be a symptom of esophageal foreign bodies. Pediatric surgeons should be aware that foreign bodies can be lodged at the entrance or within an esophageal diverticulum.

Abstract Background Mental health is a vital part of an individual’s overall health and well-being, and the relationship between society and individuals has always been a focus of academic and public attention. However, the effect of social equity perceptions on individual mental health remains unclear. Methods Data were collected from 8,922 survey respondents with an average age of 47.533 years from the China Labor-force Dynamics Survey 2016 and 2018. The Center for Epidemiological Studies Depression scale was used to assess mental health. A two-way fixed effects regression model was used to determine the association between social equity perception and individual mental health. Results Individuals with higher perceptions of social equity were more likely to report better mental health ( $$\beta$$ β = -0.944, p < 0.01). Happiness, life satisfaction, and social trust partially play mediating roles in the relationship between social equity perception and individual mental health, while education and age play moderating roles. Conclusion Social equity perception is a vital factor that affects mental health. Public policies should focus on helping less educated and older people improve their social equity perception to improve their mental health.

ObjectiveThe pandemic of COVID-19 continues to challenge people's health worldwide. In the second year of the pandemic, adherence to COVID-19 preventive behavior is key to continuing efforts to overcome the epidemic. This study aims to assess the COVID-19-related knowledge, attitude, and prevention behavior (KAP) and electronic health literacy (eHealth literacy) among Anhui residents in China.MethodsFrom January 30 to March 27, 2021, the cross-sectional study was performed among Anhui residents in China, including 16 cities. An online survey was adopted to assess KAP regarding COVID-19, and eHealth, involving a total of 2,122 citizens. Following informed consent, residents were recruited by convenience sampling. Frequencies and proportions were calculated. Additionally, Mann–Whitney U tests were used to analyze the variables. Independent predictors of preventive behavior of COVID-19 were ascertained using a multivariable logistic regression model.ResultResidents demonstrated good knowledge, positive attitudes, acceptable practices, and good eHealth literacy. Online news and WeChat are the main health information resources. Citizens who had good knowledge, a positive attitude, good eHealth, and did not participate in the online lectures or training COVID-19 were more likely to take preventive measures. Those with poor health, who were male, did not have family members working in health care facilities, and did not work in a face-to-face environment were less likely to take precautions. Compared with a master's degree and above, participants with middle school education level and below took preventive behavior sometimes. Residents who browse the COVID-19 webpage

Water rights for environmental flows are not universal, and oftentimes, legal tools used to incorporate the environment into water management only require new users to consider their impact. It can be difficult to include the needs of riparian and aquatic ecosystems in new plans when relevant information is not always available, especially when other existing uses already outstrip available supplies. There is a need for easily accessible and understandable science on the water requirements for riparian and aquatic species, so managers can make informed decisions about whether or not to include riparian and aquatic species in their community's water management future. In this paper, we describe the current understanding of the link between hydrology and Arizona's riparian and aquatic ecosystems through the creation of a geospatial Environmental Water Demands database that can be used to determine the water needs to maintain habitat. Analysis of 121 studies reveals that there are very few analyses of the surface water and groundwater requirements for intermittent or ephemeral river systems, and there are only limited generalizable data for aquatic species. Except for a few species, such as Cottonwood ( Populous fremontii) and Willow ( Salix gooddingii), few data are available on the flow requirements for vegetation. The Environmental Water Demands database can be used to identify critical geographic and topical knowledge gaps where further research is needed, as well as serve as a single place for water and land managers to assess and use the most currently available information to make more informed management decisions and recommendations. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Maritime moving targets continuation observation has important implications to maintain the safety of the navigation barrier. Existing methods either rely on satellite observations, or only rely on UAV observations. Even though the two cooperative observations, it confined to a simple task allocation. They did not solve the problem of maritime moving targets continuation observation. On the basis of difference between satellites observation and UAV observation, we constructed the aerospace collaborative continuation observation model for maritime moving target, and put forward aerospace collaborative continuation observation strategy (ACCOS) to reduce the complexity of solving the model. According to the spatial and temporal characteristics of the task, ACCOS extracted five sub problems to solve the model: Satellite planning, UAV flight plan, UAV observation sequence, target potential area and distribution probability density prediction, UAV path planning. In order to realize the optimization goal of the model, the five sub problems are modelled and solved in turn. Finally, the simulation results show that the proposed method can greatly reduce the average observation period of the target, and effectively solve the problem of the continuous observation of maritime moving target.

Abstract Aim To investigate the enhancement of humoral immunity when CpG ODN (cytidine phosphate guanosine oligodeoxynucleotides) and aluminium adjuvants are complexed with the HCV (Hepatitis C virus) recombinant immunogen in mice. Methods After immunizing Balb/c mice with the recombination HCV antigen adjuvanted with pUCpGs10 and/or aluminium(antigen+CpG+alum, antigen+CpG, antigen+alum, antigen+PBS), enzyme-linked immunosorbent assay (ELISA) was used to measure the specific serum antibody titers of IgG, to determine the neutralization response to various peptide genotypes, and to determine the concentration of IL-6 and IL-10 in supernatants of in vitro cultured splenic lymphocytes. Enzyme-linked immunospot assay (ELISPOT) was used to quantify the non-specific and specific splenic antibody-secreting cells (ASCs), and flow cytometry (FCM) determined the ratio of different splenic lymphocytes. The serum of rabbits immunized with the recombinant pBVGST/HVR1 antigen immunoprecipitated the HCV isolated from 12 patients' serum. Results The sera antibody titers were 1:51200, 1:9051, 1:18102, 1:6400 respectively after the final immunization and demonstrated good neutralization responses to the six gene peptide containing 1a, 1b, 2a, 3a, 4a and 6a. The aluminum adjuvant increased the population of both specific ASCs (P < 0.01) and total ASCs(P < 0.05), with a proportional rise in concentrations of CD19+CD27+ (P < 0.05), as well as levels of IL-6, IL-10 (P < 0.05) in splenic lymphocytes. The results clearly indicated a significantly higher number of CD19+CD38+ splenic lymphocytes with the aluminum and pUCpGs10 adjuvant present compared to the control group(P < 0.05). Anti-HVR1 antibody in induced mice can cross-reactively capture HCV particles (10/12). Conclusions 1. The aluminum adjuvant induces a potent Th2-biased immune response by increasing both the populations of specific and total ASCs and the ratio of CD19+CD27+ cells. 2. The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response. 3. The two adjuvants have synergistic effects on humoral immunity. 4. The recombinant HVR1 protein has the possibility of generating broadly reactive anti-HVR1 antibody.

Atherosclerosis (AS) is a chronic inflammatory disease of arteries. Endothelial inflammation is key to the initiation and development of AS. The calcium-sensing receptor (CaSR) is expressed in endothelial cells (ECs) but its role in endothelial inflammation during AS remains unclear. This study focused on the involvement of CaSR in regulating endothelial inflammation and its underlying mechanisms, providing novel insights for AS therapy. Here, we observed that CaSR agonist NPS-R568 significantly reduced atherosclerotic lesions and aortic inflammation in high-fat diet (HFD)-fed ApoE -/- mice, while enhancing the expression of CaSR in aortic tissues. In vitro, human umbilical vein endothelial cells (HUVECs) exposed to oxidized low-density lipoprotein (oxLDL) at 20 μg·mL -1 triggered inflammation, as indicated by the upregulation of vascular cell adhesion molecule-1 (VCAM-1), interleukin (IL)-6, and IL-1β expression, along with increased adherence of THP-1 or U937 cells to the HUVECs. Additionally, treatment with 20 μg·mL -1 oxLDL led to downregulation of CaSR expression in HUVECs. The administration of CaSR agonist NPS-R568 or overexpression of CaSR in HUVECs resulted in a significant reversal of inflammation induced by oxLDL. Mechanistically, CaSR was found to mitigate NLRP3 inflammasome activation by downregulating the protein level of integrin β1. In conclusion, our study elucidates the beneficial role of CaSR in reducing endothelial inflammation in AS through the regulation of integrin β1 and the subsequent NLRP3 inflammasome. CaSR emerges as a promising target for potential therapeutic interventions in AS., (© 2024 Federation of European Biochemical Societies.)

Background: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma., Methods: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control., Results: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively., Conclusions: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Burkitt lymphoma (BL) is a highly aggressive type of non-Hodgkin lymphomas that have a high likelihood of relapse and are highly refractory to initial treatment. While high-intensity chemotherapy has improved the outcomes, many adult patients still experience treatment failure, and effective salvage therapies are limited. This study retrospectively analyzed the outcomes of 21 relapsed or refractory (R/R) adult BL patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, combined or not with hematopoietic cell transplantation (HCT), across four Chinese hospitals. Patients were grouped based on treatment strategies: autologous HCT followed by CAR T-cell therapy (auto-HCT+CART group, n = 8), and CAR T-cell therapy alone (CART group, n = 13). The auto-HCT+CART group demonstrated superior outcomes, with an overall response rate (ORR) of 87.5 % and significantly higher 1-year overall survival (OS) and progression-free survival (PFS) rates compared to the CART group (p = 0.014 and p = 0.045, respectively). These findings suggest that combining auto-HCT with CAR-T therapy may enhance long-term disease control in R/R BL patients. These encouraging results highlight the need for further prospective studies to validate our data., Competing Interests: Declaration of competing interest No relevant conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

Seawater physicochemical parameters and environmental capacity are important ecological indicators and typical features of the marine environment. It has great significance in the marine material cycle and ecological health. In September 2021 (wet season) and March 2022 (dry season), two voyage investigations were conducted at 12 stations (D1-D12) on Dapeng Bay (DPB), northern South China Sea. The distribution of nutrient, water-quality status, environmental capacity, and impact of ecological environment were discussed. Results showed that NH 4 -N was the main form of dissolved inorganic nitrogen (DIN) during the wet season, with concentrations ranging from 0.008 mg/L to 0.109 mg/L, accounting for ~53 % of DIN. Conversely, NO 3 -N was the main form of DIN during the dry season, with concentrations ranging from 0.005 mg/L to 0.117 mg/L, accounting for ~50 % of DIN. The DIP concentration ranged from 0.002 mg/L to 0.019 mg/L, accounting for ~51 % and 31 % of the total dissolved phosphorus in the wet and dry seasons, respectively. The distributions of NH 4 -N, NO 3 -N, NO 2 -N, and DIP were relatively similar, decreasing from the inner bay to the outer bay. The eutrophication indices of 12 stations <1, indicating a poor eutrophication state. Single-factor indices including chemical oxygen demand (COD), DIN, and dissolved inorganic phosphorus (DIP) were less than the class I seawater-quality standard. However, except for station D1, the overall water quality was good. Dissolved oxygen with DIP had a significantly negative correlation during the dry season, indicating that DIP was primarily dominated by marine biological activity and organic-matter decomposition. The remaining environmental capacities of COD, DIN, and DIP in DPB were calculated to be 13,742, 1418, and 141 tons, respectively. Based on the functional-zone division of the sea area, the remaining environmental capacities of COD, DIN, and DIP were exceeded 75 % of the total environmental capacity. This study provided a scientific basis for the protection of marine ecological environment and the sustainable development of DPB., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Object: Autologous CD19 chimeric antigen receptor T-cell therapy (CAR-T) significantly modifies the natural course of chemorefractory diffuse large B-cell lymphoma (DLBCL). However, 25% to 50% of patients with relapsed/refractory DLBCL still do not achieve remission. Therefore, investigating new molecular prognostic indicators that affect the effectiveness of CAR-T for DLBCL and developing novel combination therapies are crucial., Methods: Data from 73 DLBCL patients who received CD19 CAR-T (Axi-cel or Relma-cel) were retrospectively collected from Shanghai Tongji Hospital of Tongji University, The Second Affiliated Hospital Zhejiang University School of Medicine, and The Affiliated People's Hospital of Ningbo University. Prior to CD19 CAR-T-cell transfusions, the patients received fludarabine and cyclophosphamide chemotherapy regimen., Results: Our study revealed that relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) patients with both Double-expression (MYC > 40% and BCL2 > 50%) and TP53 alterations tend to have a poorer clinical prognosis after CAR-T therapy, even when CAR-T therapy is used in combination with other therapies. However, CAR-T therapy was found to be effective in patients with only TP53 alterations or DE status, suggesting that their prognosis is in line with that of patients without TP53 alterations or DE status., Conclusions: Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Breast cancer (BC) poses a global threat, with HER2-positive BC being a particularly hazardous subtype. Despite the promise shown by neoadjuvant therapy (NAT) in improving prognosis, resistance in HER2-positive BC persists despite emerging targeted therapies. The objective of this study is to identify markers that promote therapeutic sensitivity and unravel the underlying mechanisms., Methods: We conducted an analysis of 86 HER2-positive BC biopsy samples pre-NAT using RNA-seq. Validation was carried out using TCGA, Kaplan‒Meier Plotter, and Oncomine databases. Phenotype verification utilized IC 50 assays, and prognostic validation involved IHC on tissue microarrays. RNA-seq was performed on wild-type/DUSP4-KO cells, while RT‒qPCR assessed ROS pathway regulation. Mechanistic insights were obtained through IP and MS assays., Results: Our findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER2-positive BC. Moreover, DUSP4 hinders G6PD activity via ALDOB dephosphorylation, with a noteworthy association with heightened ROS levels., Conclusions: In summary, our study unveils a metabolic reprogramming paradigm in BC, highlighting DUSP4's role in enhancing therapeutic sensitivity in HER2-positive BC cells. DUSP4 interacts with ALDOB, inhibiting G6PD activity and the ROS pathway, establishing it as an independent prognostic predictor for HER2-positive BC patients., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To review the development of endoscopic techniques in breast surgery, focusing on their use in benign breast lump resection and breast-conserving surgery for cancer, and also summarize the development and application of these techniques in China, highlighting promotion and homogenization challenges and future directions., Methods: A systematic review of relevant literature was conducted to trace the historical evolution, clinical applications, and related research of endoscopic techniques in breast surgery, emphasizing their advantages and disadvantages of endoscopic benign breast lump resection and breast-conserving surgery for cancer., Results: Endoscopic benign breast lump resection and breast-conserving surgery for cancer have improved patients' postoperative psychological health and quality of life, particularly in scar-free surgery. However, challenges such as limited intraoperative visibility and prolonged surgery time lead to controversy in clinical practice., Conclusion: Despite significant advancements, endoscopic techniques in breast surgery also face challenges. Future efforts should focus on technological improvements and clinical research to address these issues, promoting widespread application and standardization. The key to future development lies in the promotion and homogenization of these technologies.

Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC., Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154)., Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2)., Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation., Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication., (© 2024 Published by Elsevier Ltd.)

The immunomodulatory (IM) subtype of triple negative breast cancer (TNBC) exhibits high expression of immune cell signaling genes and is more responsive to immunotherapy. However, the specific mechanism underlying this phenomenon remains unclear. One of the potential key genes appears to be the cytotoxic and regulatory T cell molecule (CRTAM). A cohort of 360 previously untreated TNBC patients from Fudan University Shanghai Cancer Center (FUSCC) underwent RNA sequencing analysis of their primary tumor tissue. Combined with three RNA-seq datasets obtained from the GEO database, a LASSO regression analysis was conducted to identify genes specific to the IM type of TNBC. Our findings revealed elevated CRTAM expression in the IM-type TNBC, which correlated with a favorable overall survival and recurrence-free survival in TNBC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated a strong association between CRTAM and immune responses as well as immune system processes. Notably, CRTAM overexpression induced STAT1 phosphorylation and upregulation of interferon-stimulated genes. We also found that CRTAM enhanced tumor-associated immune cell infiltration, especially CD8 + T cells, which may be related to the increased expression of MHC class I molecules caused by CRTAM overexpression. These results suggest that CRTAM may serve as a potential biomarker for predicting the efficacy of immunotherapy in TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Huanglongbing (HLB) (caused by Candidatus Liberibacter asiaticus) is the most damaging disease of citrus around the world. This study investigated the effects of citrus tree height on Diaphorina citri Kuwayama mortality, endosymbiont responses, and HLB distribution., Results: The results reveal that the age of citrus trees plays a significant role in psyllid mortality. Interestingly, the cumulative mean mortality (%) of psyllids over the seven-day observation period was higher (31.50±0.03) when four-year-old (501A1, 502A2, 501A3) citrus trees were sprayed with a US-SMART mechanical sprayer. In contrast, the psyllids mortality was 0.09±0.23 for the 13-year-old citrus trees (104A2, 104A3, 104C1) sprayed with a US-SMART mechanical sprayer and 9.10±0.05 for 13-year-old (502A2, 502B2, 502D1) citrus trees sprayed with a fixed US-SMART mechanical sprayer. Our findings also revealed that psyllids from both four- and 13-year-old citrus trees carried Candidatus Carsonella ruddii species and Wolbachia, the primary and secondary endosymbionts, respectively. Surprisingly, infection rates of these endosymbionts remained consistent across different age groups, as confirmed by quantitative polymerase chain reaction analysis. Furthermore, our study highlights the significance of tree height as a proxy for tree age in influencing HLB occurrence. Specifically, four-year-old citrus trees subjected to the US-SMART mechanical sprayer for citrus psyllid control demonstrated effective disease management compared to 13-year-old (104A2, 104A3, 104C1) citrus trees sprayed with US-SMART mechanical sprayers. Additionally, the investigation explored the impact of tree height on HLB distribution. In four-year-old trees, no significant correlation between HLB disease and tree height was observed, potentially due to effective spray coverage with US-SMART mechanical sprayer. However, in 13-year-old (104A2, 104A3, 104C1) citrus tree sprayed with US-SMART mechanical sprayer, a positive correlation between tree height and HLB disease was evident., Conclusion: This research provides valuable insights into the complex interaction between citrus tree age, psyllid endosymbionts responses, and HLB distribution. These results emphasize effective HLB management strategies, especially in orchards with diverse tree age populations, ultimately contributing to the long-term sustainability of citrus cultivation. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objective: To study the classification, diagnosis, and treatment strategies of complex tethered cord syndrome (C-TCS) on the basis of the patients' clinical symptoms, imaging findings, and therapeutic schedule., Methods: The clinical data of 126 patients with C-TCS admitted to our department from January 2015 to December 2020 were retrospectively analyzed. Classification criteria for C-TCS were established by analyzing the causes of C-TCS. Different surgical strategies were adopted for different types of C-TCS. The Kirollos grading, visual analogue scale (VAS), critical muscle strength, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the surgical outcomes and explore individualized diagnosis and treatment strategies for C-TCS., Results: C-TCS was usually attributable to three or more types of tether-causing factors. The disease mechanisms could be categorized as pathological thickening and lipomatosis of the filum terminal (filum terminal type), arachnoid adhesion (arachnoid type), spina bifida with lipomyelomeningocele/meningocele (cele type), spinal lipoma (lipoma type), spinal deformity (bone type), and diastomyelia malformation (diastomyelia type). Patients with different subtypes showed complex and varied symptoms and required individualized treatment strategies., Conclusion: Since C-TCS is attributable to different tether-related factors, C-TCS classification can guide individualized surgical treatment strategies to ensure complete release of the tethered cord and reduce surgical complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lin, Su, Li, Zhang, Xiu, Bai and Xu.)

Background: Gene mutations play a crucial role in the occurrence and development of tumors, particularly in breast cancer (BC). Neoadjuvant therapy (NAT) has shown greater clinical benefit in HER2-positive breast cancer. However, further clinical investigation is needed to fully understand the correlation between genetic mutations and NAT efficacy and the long-term prognosis in HER2-positive BC., Methods: This was a retrospective cohort study of 222 patients receiving NAT between 2017 and 2021 in the Department of Breast Surgery of Fudan University Shanghai Cancer Center. Tumor samples from these patients were subjected to Next Generation Sequencing (NGS) to analyze mutations in 513 cancer-related genes. This study aimed to investigate the association between these genetic mutations and postoperative pathological complete response (pCR), as well as their impact on disease-free survival (DFS)., Results: In total, 48.65% patients reached pCR, ER-negative status (p < 0.001), PR-negative status (p < 0.001), Ki67 ≥ 20 (p = 0.011), and dual-targeted therapy (p < 0.001) were all associated with enhanced pCR rates. The frequency of somatic alterations in TP53 (60%), PIK3CA (15%), and ERBB2 (11%) was highest. In the HER2+/HR- cohort, patients who achieved pCR had a significant benefit in prognosis (HR = 3.049, p = 0.0498). KMT2C (p = 0.036) and TP53 (p = 0.037) mutations were significantly increased in patients with DFS events. Moreover, TP53 mutations had prognostic significance in HER2-positive BC patients with HR-negative (HR = 3.712, p = 0.027) and pCR (HR = 6.253, p = 0.027) status and who received herceptin-only targeted therapy (HR = 4.145, p = 0.011)., Conclusions: The genetic mutation profiles of Chinese HER2+ patients who received NAT were discrepant with respect to HR status or DFS events. TP53 mutations have significant prognostic value in patients with NAT for HER2-positive BC and patients benefit differently depending on HR status, the neoadjuvant regimen and response, which highlights the significance of genetic factors in treatment customization based on individual genetic and clinical characteristics., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Although targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly prolonged survival time and improved patients' quality of life, drug resistance has gradually emerged. This study explored the mechanisms underlying the effect of the motor neuron and pancreatic homeobox 1 ( MNX1 ) genes on drug sensitivity in HER2-positive breast cancer. From July 2017 to 2018, core needle biopsies of HER2-positive breast cancer were collected from patients who received paclitaxel, carboplatin, and trastuzumab neoadjuvant therapy at our center. Based on treatment efficacy, 81 patients were divided into pathological complete response (pCR) and non-pCR groups. High-throughput RNA sequencing results were analyzed along with the GSE181574 dataset. MNX1 was significantly upregulated in the pCR group compared with the non-pCR group in both sequencing datasets, suggesting that MNX1 might be correlated with drug sensitivity in HER2-positive breast cancer. Meanwhile, tissue array results revealed that high MNX1 expression corresponded to a good prognosis. In vitro functional tests showed that upregulation of MNX1 significantly increased the sensitivity of HER2-positive breast cancer cells to lapatinib and pyrotinib. In conclusion, MNX1 may serve as a prognostic marker for patients with HER2-positive breast cancer, and its expression may facilitate clinical screening of patients sensitive to anti-HER2-targeted therapy.

Background: Breast reconstruction has become an integral component of breast cancer treatment, especially for patients who are unable to undergo breast-conserving surgery after neoadjuvant chemotherapy (NAC). We analyzed factors influencing the type of immediate reconstruction surgery after NAC, as well as the complication rates for each surgery type., Methods: The study included patients with breast cancer who underwent mastectomy following NAC from 2010 to 2021. Clinicopathological characteristics, unplanned reoperation rates, and the duration of postoperative hospitalization were analyzed in patients undergoing autologous tissue reconstruction (ATR, n = 127), implant-based reconstruction (IBR, n = 60), and combined autologous tissue and implant reconstruction (n = 60)., Results: A total of 1651 patients who received NAC before mastectomy were enrolled. Among them, 247 (15.0%) patients underwent immediate reconstruction (IR), whereas 1404 underwent mastectomy only. Patients in the IR group were younger ( P < 0.001), had lower body mass index ( P < 0.001), and exhibited earlier clinical ( P = 0.003) and nodal ( P < 0.001) stage than those in the non-IR group. Patients in the ATR group were older ( P < 0.001) and had higher body mass index ( P = 0.007), larger tumor size ( P = 0.024), and more frequent childbearing history ( P = 0.011) than those in the other groups. Complications resulting in unplanned reoperations were more frequent in the IBR group ( P = 0.039). The duration of postoperative hospitalization was longest after ATR ( P = 0.008)., Conclusions: Age and clinical tumor/nodal stage at presentation are associated with IR for patients undergoing mastectomy after NAC. For patients undergoing IR after NAC, ATR may be safer and more suitable than IBR., Competing Interests: Conflicts of interest: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

It has been reported that arsenic trioxide (ATO) regulates lymphoma cell cycle, apoptosis, autophagy and mitochondrial activity, while it synergizes with other cytotoxic agents. In addition, ATO targets anaplastic lymphoma kinase (ALK)-fusion oncoprotein to repress anaplastic large cell lymphoma (ALCL). The current study aimed to investigate the efficacy and safety of ATO plus etoposide, solumedrol, high-dose cytarabine and cisplatin (ESHAP) chemotherapy compared with ESHAP chemotherapy alone in patients with relapsed or refractory (R/R) ALK + ALCL. A total of 24 patients with R/R ALK + ALCL were enrolled in the present study. Among them, 11 patients were treated with ATO plus ESHAP, while the remaining 13 patients received ESHAP chemotherapy alone. Subsequently, treatment response, event-free survival (EFS), overall survival (OS) and adverse event (AEs) rates were recorded. Both complete response (72.7% vs. 53.8%; P=0.423) and objective response (81.8% vs. 69.2%; P=0.649) rates were higher in the ATO plus ESHAP group compared with the ESHAP group. However, statistical significance was not reached. In addition, EFS was significantly prolonged (P=0.047), while OS was not significantly increased (P=0.261) in the ATO plus ESHAP group compared with the ESHAP group. More specifically, the 3-year accumulating EFS and OS rates were 59.7 and 77.1% in the ATO plus ESHAP group, respectively, and 13.8 and 59.8% in the ESHAP group, respectively. The majority of AEs, such as thrombocytopenia (81.8% vs. 46.2%; P=0.105), fever (81.8% vs. 46.2%; P=0.105) and dyspnea (36.4% vs. 15.4%; P=0.182), were more prevalent in the ATO plus ESHAP group compared with the ESHAP group. However, no statistical significance was observed. In conclusion, the current study indicated that ATO plus ESHAP chemotherapy could exert a superior efficacy compared with ESHAP chemotherapy alone in patients with R/R ALK + ALCL., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ding et al.)

Background: Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown., Methods: The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 5'/3' RACE. Paired-guide CRISPR/cas9 and CRISPR/dead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays., Results: Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478&#95;FL) was cleaved and polyadenylated, simultaneously yielding 5' ends stable expressing LacRNA, which is released into the cytoplasm, and long 3' ends of nuclear-retained lncRNA. LINC00478&#95;3'RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61-140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model., Conclusion: Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy., (© 2023. The Author(s).)

There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and "real-world" listening environments and stimuli. Speech in the real world is often accompanied by visual cues, background environmental noise, and is generally in a conversational context, all factors that could affect listening demand. Thus, our objectives were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high-density electroencephalogram (EEG) while CI users listened/watched a naturalistic stimulus (i.e., the television show, "The Office"). We used continuous EEG to quantify "speech neural tracking" (i.e., TRFs, temporal response functions) to the show's soundtrack and 8-12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show, mimicking a natural noisy environment. The task also included an audio-only (no video) condition. After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they understood. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). Increasing background noise affected speech neural tracking at a group level, in addition to eliciting strong individual differences. Mixed effect modeling showed that listening demand and conversation understanding were correlated to early cortical speech tracking, such that high demand and low conversation understanding occurred with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power, where higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between clinical speech perception and quality-of-life in CI users. However, physiological responses to complex natural speech may provide an objective measure of aspects of quality-of-life measures like self-perceived listening demand., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiu, Paul, Chen, Le, Lin and Dimitrijevic.)

Background: Despite the success of HER2-targeted therapy in achieving prolonged survival in approximately 50% of treated individuals, treatment resistance is still an important challenge for HER2+ breast cancer (BC) patients. The influence of both adaptive and innate immune responses on the therapeutic outcomes of HER2+BC patients has been extensively demonstrated., Methods: Long non-coding RNAs expressed in non-pathological complete response (pCR) HER2 positive BC were screened and validated by RNA-seq. Survival analysis were made by Kaplan-Meier method. Cell death assay and proliferation assay were performed to confirm the phenotype of LINC00624. RT-qPCR and western blot were used to assay the IFN response. Xenograft mouse model were used for in vivo confirmation of anti-neu treatment resistance. RNA pull-down and immunoblot were used to confirm the interaction of ADAR1 and LINC00624. ADAR1 recombinant protein were purified from baculovirus expression system. B16-OVA cells were used to study antigen presentation both in vitro and in vivo. Flow cytometry was used to determine the tumor infiltrated immune cells of xenograft model. Antisense oligonucleotides (ASOs) were used for in vivo treatment., Results: In this study, we found that LINC00624 blocked the antitumor effect of HER2- targeted therapy both in vitro and in vivo by inhibiting type I interferon (IFN) pathway activation. The double-stranded RNA-like structure of LINC00624 can bind and be edited by the adenosine (A) to inosine (I) RNA-editing enzyme adenosine deaminase RNA specific 1 (ADAR1), and this editing has been shown to release the growth inhibition and attenuate the innate immune response caused by the IFN response. Notably, LINC00624 promoted the stabilization of ADAR1 by inhibiting its ubiquitination-induced degradation triggered by β-TrCP. In contrast, LINC00624 inhibited major histocompatibility complex (MHC) class I antigen presentation and limited CD8+T cell infiltration in the cancer microenvironment, resulting in immune checkpoint blockade inhibition and anti-HER2 treatment resistance mediated through ADAR1., Conclusions: In summary, these results suggest that LINC00624 is a cancer immunosuppressive lncRNA and targeting LINC00624 through ASOs in tumors expressing high levels of LINC00624 has great therapeutic potential in future clinical applications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)