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Abstract Background Chloroplast development is coordinately regulated by plastid- and nuclear-encoding genes. Although many regulators have been reported to be involved in chloroplast development, new factors remain to be identified, given the complexity of this process. Results In this study, we characterized a rice mutant lethal albinic seedling 1(las1)form of a 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (OsHMBPP) that was targeted to the chloroplasts. The LAS1 mutation caused the albino lethal phenotype in seedlings. Transmission electron microscopy indicated that las1 were defective in early chloroplast development. LAS1 is preferentially expressed in leaves, implying its role in controlling chloroplast development. The expression levels of many chloroplast-encoded genes were altered significantly in las1. The expression levels of nuclear-encoded gene involved in Chl biosynthesis were also decreased in las1. We further investigated plastidic RNA editing in las1 and found that the edit efficiency of four chloroplast genes were markly altered. Compared with WT, las1 exhibited defective in biogenesis of chloroplast ribosomes. Conclusions Our results show that LAS1/OsHMBPP plays an essential role in the early chloroplast development in rice.

Selenium (Se) is an essential trace element for humans and animals. A hydroponic experiment was performed to study the effects of sulphur (S) on Se uptake, translocation, and assimilation in wheat (Triticum aestivum L.) seedlings. Sulphur starvation had a positive effect on selenate uptake and the form of Se supplied greatly influenced Se speciation in plants. Compared with the control plants, Se uptake by the S-starved plants was enhanced by 4.81-fold in the selenate treatment, and selenate was readily transported from roots to shoots. By contrast, S starvation had no significant effect on selenite uptake, and selenite taken up by roots was rapidly converted to organic forms and tended to accumulate in roots. X-ray absorption near edge spectroscopy (XANES) analysis showed that organic forms of selenium, including selenocystine, Se-methyl-selenocysteine (MeSeCys), and selenomethionine-Se-oxide, were dominant in the plants exposed to selenite and accounted for approximately 90 % of the total Se. Whereas selenate remained as the dominant species in the roots and shoots exposed to selenate, with little selenate converted to selenite and MeSeCys. Besides, sulphur starvation increased the proportion of inorganic Se species in the selenate-supplied plants, but had no significant effects on Se speciation in plants exposed to selenite. The present study provides important knowledge to understand the associated mechanism of Se uptake and metabolism in plants.

Objective: To analyze the efficacy of endoscopic surgery for frontal sinus meningoencephalocele and cerebrospinal fluid (CSF) leaks, and to explore endoscopic surgical strategy. Methods: A total of 35 patients with frontal sinus meningoencephalocele and CSF leaks who underwent endoscopic transnasal surgery at Beijing Tongren Hospital, Capital Medical University between May 2007 and December 2023 were enrolled in this retrospective case series, including 29 males and 6 females, with the age of (35.23±15.76) years. High-resolution sinus CT and magnetic resonance cisternography were undertaken before surgery. The primary outcome measure was the success rate of endoscopic surgical repair. Statistical analysis was conducted using SPSS 27 and GraphPad Prism 8 software. Results: Of the 35 cases, 21 (60.0%) were traumatic, and 14 (40.0%) were non-traumatic. The most common defect was in the posterior frontal sinus wall (24 cases, 68.6%), with a defect size of (10.4±4.8) mm 2 . Twenty-six cases (74.3%) underwent endoscopic transnasal Draf Ⅱa-Ⅲ frontal sinusotomy, and 9 cases (25.7%) underwent endoscopic transnasal Darf Ⅱb-Ⅲ frontal sinusotomy combined with frontal trephination. The average follow-up time was (84.72±57.42) months. The success rate of one-time endoscopic repair was 97.1% (34/35). One patient required a second procedure, resulting in an overall success rate of 100%. Thirty-three patients had a widely patent frontal sinus ostium postoperatively, while two experienced stenosis. Conclusions: Endoscopic surgery is effective for treating frontal meningoencephalocele and CSF leaks while preserving frontal sinus drainage. Combined frontal trephination is recommended for defects that are difficult to repair using the conventional transnasal approach.

Background: The recommended first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients is EGFR-tyrosine kinase inhibitors (EGFR-TKIs). BRAF alterations have been identified as resistance mechanisms. We aimed to identify features of and subsequent treatment strategies for such patients., Patients and Methods: We conducted a systematic literature review of NSCLC patients harboring acquired BRAF alterations. Additionally, BRAF-altered NSCLC patients who progressed from EGFR-TKIs at West China Hospital of Sichuan University were screened. Patient characteristics, treatment options, and outcomes were analyzed., Results: A total of 104 patients were included, 2 of whom came from our center. Seventy-five patients (72.1%) harbored BRAF mutations (57 class I mutations, 7 class II mutations, 9 class III mutations, and 2 non-class I-III mutations), and 29 (27.9%) harbored BRAF fusions. Eighteen patients received triple-targeted therapy, including prior EGFR-TKIs plus dabrafenib and trametinib, and 23 patients received other treatments. The median progression-free survival was significantly longer in patients receiving triple-targeted therapy than in those receiving other treatments (8.0 versus 2.5 months, P < 0.001). Similar findings were observed in patients with BRAF mutations (9.0 versus 2.8 months, P = 0.004), particularly in those with BRAF class I mutations (9.0 versus 2.5 months, P < 0.001). A potential benefit was also observed among patients with BRAF fusions (5.0 versus 2.0 months, P = 0.230). Twenty patients (48.8%) experienced adverse events. Dose reduction of RAF or MEK inhibitor was required in five patients (12.2%). Five patients (12.2%) permanently discontinued treatment (three on triple-targeted therapy; one on prior EGFR-TKI plus vemurafenib; one on prior EGFR-TKI plus trametinib)., Conclusions: BRAF alterations, specifically BRAF mutations and BRAF fusions, facilitate resistance to EGFR-TKIs. Triple-targeted therapy is effective and safe for patients with EGFR-mutant NSCLC with acquired BRAF alterations, mainly among patients with BRAF class I mutations and potentially in patients with BRAF fusions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Takayasu's arteritis-pulmonary artery involvement (TA-PAI) is a chronic, progressive, inflammatory disease affecting the pulmonary artery and its branches. Patients typically present with non-specific respiratory symptoms, such as fever, dyspnea, and chest pain, leading to a high rate of misdiagnosis. The diagnosis of TA-PAI is currently based on the diagnostic criteria of aortitis and imaging evidence of pulmonary artery involvement. However, pulmonary artery involvement is not typically included in the diagnostic criteria for aortitis, which may lead to a significant underestimation of the diagnostic rate of TA-PAI, particularly in cases where pulmonary artery involvement is the only manifestation. This article reports the case of a 26-year-old female patient who presented with recurrent chest pain and fever. She was initially diagnosed with pneumonia in a foreign hospital but did not show significant improvement after four months of treatment. Eventually, she was diagnosed with pulmonary artery involvement in aortitis and was stabilized with hormones, immunosuppressive drugs, and pulmonary vascular intervention. By analyzing the clinical features and diagnostic and therapeutic approaches of this case, and reviewing the relevant literature, clinicians can improve their understanding of TA-PAI.

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [ M ( Q 1 , Q 3 )] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P >0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P =0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference ( P =0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission ( OR =0.126, 95% CI : 0.025-0.629). FLT3 mutation was not conducive to morphological remission ( OR =5.832, 95% CI : 1.778-19.124) and negative MRD ( OR =4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

Objective: To investigate the epidemiological and clinical characteristics of RSV among patients aged ≥60 years in Beijing from 2015 to 2023. Methods: Based on the respiratory pathogen surveillance system, samples of upper respiratory tract infections (URTI), non-severe community-acquired pneumonia (nsCAP) and severe community-acquired pneumonia (sCAP) among people aged ≥60 years were collected from 28 sentinel hospitals in 16 districts of Beijing from January 2015 to December 2023. Swab samples were collected from URTI within one week, and lower respiratory tract samples from nsCAP and sCAP were collected. Demographic and epidemiological data were also collected. Various respiratory pathogens including RSV were detected. Results: From January 2015 to December 2023, a total of 20 349 cases of acute respiratory infections aged ≥60 years were included, with the RSV-positive rate of 1.54% (313/20 349, 95% CI : 1.39%-1.68%). Among them, the total RSV-positive rates of older people during the pre-pandemic, pandemic, and post-pandemic periods of COVID-19 were 1.59% (207/13 006, 95% CI : 1.38%-1.81%), 0.82% (38/4 650, 95% CI : 0.56%-1.08%) and 2.53% (68/2 693, 95% CI : 1.93%-3.12%), respectively. The difference in RSV-positive rate was statistically significant ( P <0.001). Based on the sampling time of cases, the RSV epidemic season for older people in Beijing was from October to March of the following year, with a peak period in December or January of the following year. In the post COVID-19 pandemic, there were very few RSV-positive cases detected in the elderly from April to June 2023, with only one positive case detected in May and one in June. The RSV-positive rate of older people increased significantly from October to December, reaching 11.75% (51/383) in December. Among 263 RSV-positive cases in the elderly, RSV-A, RSV-B and unclassified type accounted for 43.35% (114/263), 29.28% (77/263) and 27.38% (72/263), respectively. Since 2020, there has been a subtype conversion, with RSV-B being the main focus. Among 197 elderly cases that have complete clinical data, the main symptoms were cough (86.8%, 171/197), sputum (80.2%, 158/197) and fever (73.60%, 145/197). About 24.87% (49/197) of elderly cases experienced complications. The hospitalization mortality rate was 4.57% (9/197), and the hospitalization rate was 78.68% (155/197). The ICU occupancy rate was 1.99% (36/197). The mechanical ventilation usage rate was 13.32% (33/197), and the length of hospital stay [ M ( Q 1 , Q 3 )] was 12 (9, 16) days. Conclusion: In Beijing, the RSV infection rate is relatively low during the COVID-19 pandemic, and the prevalence of COVID-19 is relatively high. In 2023, there was no out-of-season outbreak of RSV infection among the elderly. Elderly RSV infection cases have multiple complications, severe diseases, and poor prognosis.

Objective: To explore the effects of hinokiol on the cell cyle and apoptosis of CNE1 nasopharyngeal carcinoma cells and the relevant molecular mechanism. Methods: The CNE1 cells were cultured in vitro and incubated with different concentrations of honokiol, and the cells were divided into blank control group, 10 μmol/L, 20 μmol/L and 40 μmol/L hinokiol treatment groups, and 10 μg/ml cisplatin group. Cell viability was determined by methylthiazolyldiphenyl- tetrazolium bromide (MTT) method, the cell cycle distribution was detected by flow cytometry, mitochondrial membrane potential was detected by mitochondrial membrane potential test kit, apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method, and the proteins expression of proliferating cell nuclear antigen (PCNA) and G 1 /S specific cyclin D1 (cyclin D1) were detected by immunoblotting. RNA-Seq was conducted in the hinokiol-treated cells. The mRNA expression of yes-associated protein delta (YAP) was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The proteins expression of phosphor-YAP (p-YAP) and nuclear YAP were detected by immunoblotting, the nuclear distribution of YAP protein was detected by immunofluorescence in the cells with or without treated with the mammalian STE20-like kinase 1/2 (MST1/2) inhibitor (XMU-MP-1), hinokiol, and XMU-MP-1+hinokiol. Statistical analysis of the data was conducted using GraphPad Prism 8.0 software. Resluts Compared with the control group, the cell viablity of CNE1 cells, the levels of mitochondrial membrane potential, the proteins expression of PCNA and cyclin D1 in hinokiol treatment groups were markedly decreased (all P values<0.05), while the proportion of G 0 /G 1 phase cells and the ratio of TUNEL-positive cells were significantly increased (both P values<0.05). Transcriptome analysis showed that differential genes were mainly enriched in Wnt signaling pathway, tumor necrosis factor pathway, and Hippo signaling pathway. The mRNA level of YAP and the protein expression of YAP in the nucleus were decreased and the level of p-YAP protein was increased in cells treated with hinokiol, which were significantly different from control group (all P values<0.05). Compared with the hinokiol group, XMU-MP-1+hinokiol groups showed the decrease of p-YAP protein expression (1.157±0.076 vs 0.479±0.038, t =37.120, P <0.05), the increase of YAP protein expression in the nucleus (0.143±0.012 vs 0.425±0.031, t =29.181, P <0.05), the reduced proportion of cells in G 0 /G 1 phase [(72.494±3.309)% vs (58.747±2.865)%, t =17.265, P <0.05], and the decrease of apoptosis ratio [(53.158±3.376)% vs (29.621±2.713)%, t =28.584, P <0.05]. Conclusion: Hinokiol can arrest the cell cycle and induce the cell apoptosis of CNE1 cells via Hippo/YAP signaling pathway.

Objective: To investigate the regulatory role of miR-26b-3p in proliferation, migration and invasion of glioma., Methods: The expressions of miR-26b-3p and cAMP-responsive element binding protein 1 (CREB1) in gliomas of different pathological grades were detected with RT-qPCR and Western blotting. Bioinformatic methods were used to analyze the target sequence of miRNA-26b-3p binding to CREB1, and dual luciferase gene reporter experiment was performed to explore the mechanism for targeted regulation of CREB1 by miR-26b-3p. Glioma U251 cells were treated with miR-26b-3p mimic or inhibitor, and the changes in CREB1 expression and cell proliferation, migration, invasion and apoptosis were determined with Western blotting, CCK-8 assay, wound healing assay, Transwell assay, and flow cytometry., Results: The expression of miR-26b-3p decreased while CREB1 expression increased significantly as the pathological grade of gliomas increased ( P < 0.05). Dual luciferase gene reporter experiment confirmed that CREB1 was a downstream target of miR-26b-3p. Inhibition of miR-26b-3p significantly upregulated the expression of CERB1, suppressed apoptosis and promoted proliferation and invasion of glioma cells, and overexpression of miR-26b-3p produced the opposite effects ( P < 0.05)., Conclusion: MiR-26b-3p regulates CREB1 expression to modulate apoptosis, proliferation, migration and invasion of glioma cells, thereby participating in tumorigenesis and progression of glioma.

Objective: To investigate the efficacy and safety of endoscopic resection of infratemporal fossa mass and to determine the indications for surgery. Methods: A retrospective case series study was conducted, including a total of 29 patients who underwent endoscopic surgery to treat infratemporal fossa mass in the Department of Rhinology of Beijing Tongren Hospital, Capital Medical University, from April 2008 to December 2021. Ten males and 19 females were included in the study, with age of (46.5±13.7) years. Pre-and post-operative sinus CT, sinus or nasopharyngeal enhanced MRI were evaluated, respectively. The main outcome measurements were the total resection of mass and the incidence of surgery-related complications. Results: Among the 29 cases of infratemporal fossa mass, 22 were schwannomas, 3 were cysts, 2 were neurofibromas, 1 was pleomorphic adenoma and 1 was basal cell adenoma. Preoperative imaging showed well-defined lesion boundaries, and postoperative pathology confirmed the benign nature of all cases. The endoscopic transnasal approach was used in 28 patients, while the combination of the transnasal approach and the transoral approach was used in 1 patient. Complete tumor removal was achieved in all cases with a 100% resection rate. The average follow-up time was 38 months (7-168 months), and no tumor recurrence was observed. Conclusions: The Endoscopic transnasal approach is a safe and effective surgical approach for the treatment of benign tumors or masses in the infratemporal fossa.

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ 2 =1.88, 1.47, P =0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective: This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction. Methods: In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications. Results: All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case. Conclusion: The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

Aim: To develop and validate a predictive model based on 2-[ 18 F]-fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron-emission tomography (PET)/computed tomography (CT) radiomics features and clinicopathological parameters to preoperatively identify microvascular invasion (MVI) and perineural invasion (PNI), which are important predictors of poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC)., Materials and Methods: Preoperative 18 F-FDG PET/CT images and clinicopathological parameters of 170 patients in PDAC were collected retrospectively. The whole tumour and its peritumoural variants (tumour dilated with 3, 5, and 10 mm pixels) were applied to add tumour periphery information. A feature-selection algorithm was employed to mine mono-modality and fused feature subsets, then conducted binary classification using gradient boosted decision trees., Results: For MVI prediction, the model performed best on a fused subset of 18 F-FDG PET/CT radiomics features and two clinicopathological parameters, with an area under the receiver operating characteristic curve (AUC) of 83.08%, accuracy of 78.82%, recall of 75.08%, precision of 75.5%, and F1-score of 74.59%. For PNI prediction, the model achieved best prediction results only on the subset of PET/CT radiomics features, with AUC of 94%, accuracy of 89.33%, recall of 90%, precision of 87.81%, and F1 score of 88.35%. In both models, 3 mm dilation on the tumour volume produced the best results., Conclusions: The radiomics predictors from preoperative 18 F-FDG PET/CT imaging exhibited instructive predictive efficacy in the identification of MVI and PNI status preoperatively in PDAC. Peritumoural information was shown to assist in MVI and PNI predictions., (Copyright © 2023. Published by Elsevier Ltd.)

The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization. This study uses a data sample of ultraperipheral lead-lead collisions at sqrt[s&#95;{NN}]=5.02  TeV, corresponding to an integrated luminosity of 0.38  nb^{-1}, collected with the CMS experiment at the LHC. The measured second harmonic of the correlation between the sum and difference of the two jet transverse momentum vectors is found to be positive, and rising, as the dijet transverse momentum increases. A well-tuned model that has been successful at describing a wide range of proton scattering data from the HERA experiments fails to describe the observed correlations, suggesting the presence of gluon polarization effects.

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [ M ( Q 1 , Q 3 )]. The change of Ki-67 before and after NACT was statistically significant ( Z =-24.24, P <0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P <0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

Oxidative stress closely related to the progression and severity of myocardial infarction (MI). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the major enzymes that generate reactive oxygen species (ROS) in cardiovascular system. Here, we aim to elucidate the pathological role of NOX4 in MI. MI mouse model was created by the coronary artery ligation. NOX4 was specifically knocked down in heart through intramyocardial injection of siRNA. NOX4 expression and oxidative stress indicators were determined at different time points using qRT-PCR, Western blot, and ELISA, and then analyzed by Pearson's correlation. Cardiac function was evaluated by using echocardiographic technique. NOX4 was upregulated in myocardial tissues of MI mice, which positively correlated with the elevation of oxidative stress indicators. Knockdown of NOX4 in heart significantly reduced the production of ROS and the level of oxidative stress in left ventricle tissues, which was accompanied by significant improvement of cardiac function in MI mice. Selective knockdown of NOX4 in heart attenuates MI-induced oxidative stress and improves cardiac function, suggesting inhibition of NOX4/ROS axis in heart using siRNA is a potential therapeutic treatment for MI-induced cardiac dysfunction.

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees ( P <0.001), and the axial length of the right/left eye increased in various degrees ( P <0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant ( P <0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m 2 was the protective factor of eye axis length ( HR =0.778, 95% CI : 0.659-0.918, P =0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length ( HR =0.685, 95% CI : 0.592-0.793, P <0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length ( HR =0.456, 95% CI : 0.534-0.761, P <0.001; HR =0.794, 95% CI : 0.705-0.895, P <0.001; HR =0.690, 95% CI : 0.619-0.768, P <0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length ( HR =1.528, 95% CI : 1.018-2.293, P =0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length ( HR =0.542, 95% CI : 0.404-0.726, P <0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length ( HR =0.820, 95% CI : 0.698-0.965, P =0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter ( HR =0.638, 95% CI : 0.534-0.761, P <0.001; HR =0.911, 95% CI : 0.848-0.978, P =0.011; HR =0.750, 95% CI : 0.702-0.801, P <0.001). The average illumination of desktop 500- lx was a protective factor of a diopter ( HR =0.855, 95% CI : 0.763-0.958, P =0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.

Exercise can improve the cardiovascular health. However, the mechanism contributing to its beneficial effect on elderly patients with myocardial infarction is obscure. 20-month-old male Sprague-Dawley rats were used to establish myocardial infarction (MI) model by permanent ligation of the left anterior descending coronary artery (LAD) of the heart, followed by 4-week interval exercise training on a motor-driven rodent treadmill. The cardiac function, myocardial fibrosis, apoptosis, oxidative stress, and inflammatory responses were determined by using pressure transducer catheter, polygraph physiological data acquisition system, Masson's trichrome staining, and ELISA to evaluate the impact of post-MI exercise training on MI. Western blot were performed to detect the activation of AMPK/SIRT1/PGC-1alpha signaling in the hearts of aged rats. Exercise training significantly improved cardiac function and reduced the cardiac fibrosis. In infarcted heart, the apoptosis, oxidative stress, and inflammation were significantly reduced after 4-week exercise training. Mechanistically, AMPK/SIRT1/PGC-1alpha pathway was activated in the myocardial infarction area after exercise training, which might participate in the protection of cardiac function. Exercise training improves cardiac function in MI rats through reduction of apoptosis, oxidative stress, and inflammation, which may mediate by the activation of AMPK/SIRT1/PGC-1alpha signaling pathway.

Background: Large-scale preclinical Alzheimer's disease study based on β-amyloid positron emission tomography (PET) has not been conducted in China., Objectives: Establish a cohort on Alzheimer's disease spectrum, especially the preclinical stages, and determine the factors influencing the acceptance of β-amyloid PET scan screening in China., Design: Longitudinal., Setting: Shanghai, China., Participants: A total of 4386 participants were screened and 2451 participants who met enrollment criteria were eventually included in this report., Measurements: The multidimensional data was collected, including comprehensive assessments, PET and magnetic resonance imaging scans, genetics, and plasma biomarkers., Results: There were 571 participants in the normal cognition group, 625 participants in the subjective cognitive decline group, 155 participants in the objectively defined subtle cognitive decline group, 501 participants in the mild cognitive impairment group, 471 participants in Alzheimer's disease group, and 128 participants with cognitive impairment from other known causes. Significant differences in demographics, florbetapir PET, APOE, and neuropsychological tests were found among the groups. Eight hundred and seventeen participants (33.3%) completed the florbetapir PET scanning. Non-demented individuals with higher age, lower education years, male, with a family history of dementia, and higher self-report depression prefer to undergo PET scans. Acceptance of PET scans did not correlate with objectively assessed cognitive impairment., Conclusions: The Chinese Preclinical Alzheimer's Disease Study was designed to establish a large-scale cohort with comprehensive data collection. Our findings may help to understand the factors affecting the acceptance of β-amyloid PET in urban areas of China and help us address the low acceptance challenge., Competing Interests: No other disclosure was reported.

Type 2 diabetes mellitus (T2DM) is a huge challenge for global public health systems. Currently, healthcare policies advocate the prevention of the onset and progression of T2DM by improving individual lifestyles. The increasing benefits of intermittent fasting (IF) as a dietary intervention have been elucidated. However, the beneficial effects of IF in T2DM remain inconclusive. We demonstrated the physiological mechanisms underlying the positive effects of IF in T2DM. IF could trigger metabolic transformation to improve systemic metabolism and induce tissue-specific metabolic adaptations through alterations in the gut microbiota, adipose tissue remodeling, correction of circadian rhythm disturbances, and increased autophagy in peripheral tissues. The efficacy and safety of IF regimens in clinical applications carry a risk of hypoglycemia and require monitoring of blood glucose and timely adjustment of medications. However, there is limited evidence of a positive effect of IF in weight loss and improvement of glycemic variables. Overall, IF serves as a promising therapeutic target for T2DM and needs to be established by a large randomized controlled trial.

We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust.

Background: Methotrexate (MTX) is the first-line medicine to treat psoriasis. So far, there has been less research on protein biomarkers to predict its efficacy by the proteomic technique., Objectives: To evaluate differentially expressed proteins in peripheral mononuclear cells (PBMCs) between good responders (GRs) and non-responders (NRs) after MTX treatment, compared with normal controls (NCs)., Methods: We quantified protein expression of PBMCs with four GRs and four NRs to MTX and four NCs by isobaric tags for relative and absolute quantification (iTRAQ), analysing and identifying proteins related to efficacy of MTX in 18 psoriatic patients., Results: A total of 3177 proteins had quantitative information, and 403 differentially expressed proteins (fold change ≥1.2, P < 0.05) were identified. Compared to NCs, upregulated proteins (ANXA6, RPS27A, EZR, XRCC6), participating in the activation of NF-κB, the JAK-STAT pathway and neutrophil degranulation were detected in GRs. The proteins (GPV, FN1, STOM), involving platelet activation, signalling and aggregation as well as neutrophil degranulation were significantly downregulated in GRs. These proteins returned to normal levels after MTX treatment. Furthermore, Western blotting identified the expression of ANXA6 and STAT1 in PBMCs, which were significantly downregulated in GRs, but not in NRs., Conclusions: We identified seven differentially expressed and regulated proteins (ANXA6, GPV, FN1, XRCC6, STOM, RPS27A and EZR) as biomarkers to predict MTX efficacy in NF-κB signalling, JAK-STAT pathways, neutrophil degranulation, platelet activation, signalling and aggregation., (© 2022 European Academy of Dermatology and Venereology.)

Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.

Objective: To summarize the follow-up outcomes of frontal drill out procedures (draf Ⅱb, extended draf Ⅱb and draf Ⅲ) using mucosal flaps, and discuss the surgical indications of different mucosal flaps and their potential benefits to the opening of the frontal neo-ostium. Methods: A total of 48 patients with chronic rhinosinusitis or frontal mucoceles treated by draf Ⅱb, extended draf Ⅱb and draf Ⅲ between 2013 and 2019 in Beijing TongRen Hospital were enrolled in this study. Twenty-four patients who were treated with mucosal flaps were considered as mucosal flap group (including 19 males and 5 females, aging from 19 to 71 years), and the other 24 patients who didn't have neo-ostium reconstruction were considered as control group (including 18 males and 6 females, aging from 21 to 63 years). The frontal neo-ostium crosssectional area was measured with osiriX ® 7 days and 1 year postoperatively. Lund-Kennedy score (LKS) was also completed to analyze the difference of therapeutic effect between mucosal flap group and control group. SPSS 23.0 software was used for statistical analysis. Results: The postoperative follow-up time was 18 to 102 months. The postoperative epithelialization time in the mucosal flap group and the control group was (2.5±0.9) months and (3.0±0.7) months (Mean±SD), respectively, with statistically significant ( t =1.97, P =0.024). At the end of follow-up, 23 cases (95.8%) had well opened frontal neo-ostium, 1 case (4.2%) was re-stenosed, and there was no revision surgery in the mucosal flap group. In the control group, 16 cases (66.7%) had well opened frontal neo-ostium, 8 cases (33.3%) were re-stenosed, 4 cases (16.7%) had revision surgery. The mucosal flap group had much fewer stenosis cases than control group ( χ 2 =4.92, P =0.027). The neo-ostium area in the mucosal flap group and the control group was reduced by (0.87±0.58) cm 2 and (1.54±1.15) cm 2 1 year after operation respectively, with statistically significant ( t =1.72, P =0.046). There was no case of frontal sinus atresia and no surgical complication in both groups. The two-factor repeated measurement analysis of variance after surgery showed that the average LKS of the mucosal flap group was 0.78 points lower than that of the control group. In other words, the influence of grafting technique on LKS was statistically significant ( F =5.33, P =0.035). Conclusions: The application of mucosal flaps to cover the denuded bone during frontal drill out procedures can prohibit mucosal scar and new bone formation, and significantly reduce the stenosis rate of frontal neo-ostium.

Objective: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats., Methods: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation ( n =5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group ( n =5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA., Results: The rat models of ICH showed significantly increased mNSS ( P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb ( P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons ( P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 ( P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 ( P < 0.05), and increased the content of HMGB1 ( P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons ( P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 ( P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 ( P < 0.05), and reduced the content of HMGB1 in ICH rats ( P < 0.05)., Conclusion: Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.