Overview of the early campaign diagnostics for the SPARC tokamak (invited).

The SPARC tokamak is a high-field, Bt0 ∼12 T, medium-sized, R0 = 1.85 m, tokamak that is presently under construction in Devens, MA, led by Commonwealth Fusion Systems. It will be used to de-risk the high-field tokamak path to a fusion power plant and demonstrate the commercial viability of fusion energy. SPARC's first campaign plan is to achieve Qfus > 1 using an ICRF-heated, <10 MW, high current, Ip ∼ 8.5 MA, L-mode fueled by D-T gas injection, and its second campaign will investigate H-mode operations in D-D. To facilitate plasma control and scientific learning, a targeted set of ∼50 plasma diagnostics are being designed and built for operation during these campaigns. While nearly all diagnostics are based on established techniques, the pace of deployment, relative to the first plasma, and the harshness of the thermal, electromagnetic, and radiation environment are unprecedented for medium-sized tokamaks. An overview of the SPARC diagnostic set is given, providing context to further details communicated by the SPARC team in companion publications that are system-specific. The system engineering philosophy for SPARC diagnostics is outlined, and the design and engineering verification process for components inside and outside the primary vacuum boundary are described. Diagnostics are mounted directly to the vacuum vessel as well as housed within a series of eight midplane and 24 off-midplane replaceable port plugs. With limited exceptions, signal conditioning, digitization electronics and cameras as well as lasers and microwave sources are localized to a series of five Diagnostic Lab spaces, totaling ∼350 m2, located >15 m from the center of the tokamak, on the other side of a 2.4 m concrete shielding wall. A series of 31 large-scale penetrations have been included in the SPARC Tokamak Hall to facilitate integration of early campaign diagnostics and to provide upgradability.

Recursive partitioning analysis model for de novo metastatic nasopharyngeal carcinoma treated with locoregional radiotherapy following chemoimmunotherapy.

BACKGROUND: Chemoimmunotherapy is the first-line treatment of de novo metastatic nasopharyngeal carcinoma (dmNPC), with additional locoregional radiotherapy (LRRT) significantly prolonging patient survival. De novo metastatic nasopharyngeal carcinoma, however, demonstrates considerable heterogeneity, resulting in significant variability in patient outcomes. We developed and validated a prognostic tool for patients undergoing first-line chemoimmunotherapy plus LRRT and to evaluate the benefit of local therapy (LT) for distant metastases across different risk levels. PATIENTS AND METHODS: We studied 364 dmNPC patients receiving initial platinum-based chemotherapy and anti-programmed cell death protein 1 immunotherapy followed by LRRT. Patients were randomly divided into training and validation cohorts (7 : 3 ratio). The primary endpoint was progression-free survival (PFS). A prognostic model for PFS was developed using recursive partitioning analysis (RPA). RESULTS: An RPA model categorized patients into five prognostic groups based on number of metastatic lesions, liver metastasis status, and post-treatment Epstein-Barr virus DNA levels. Survival analysis identified three distinct risk groups. High-risk patients had significantly poorer PFS compared with medium- and low-risk groups (2-year PFS rate: training cohort: 13.7% versus 69.4% versus 94.4%, P < 0.001; validation cohort: 7.8% versus 65.1% versus 87.3%, P < 0.001). We investigated the impact of LT for distant metastases across these risk groups and found that only patients in the medium-risk group derived benefit from LT (2-year PFS rate: 77.5% versus 64.0%; hazard ratio = 0.535, 95% confidence interval 0.297-0.966, P = 0.035). Conversely, no survival benefit from LT for distant metastases was observed in the low-risk (P = 0.218) and high-risk subgroups (P = 0.793). CONCLUSIONS: Our RPA-based prognostic model integrates number of metastatic lesions, liver metastasis status, and post-treatment Epstein-Barr virus DNA levels to predict PFS in dmNPC patients undergoing chemoimmunotherapy plus LRRT. This model offers personalized treatment guidance, suggesting that patients in the medium-risk group may benefit from LT for distant metastases, while those in high- and low-risk groups may not.

[Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos].

Objective: To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells. Methods: In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5µg/cm(2) chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet-t test. Results: Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells (P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased (P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Conclusion: Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

Prototype optical enhancement cavity for steady-state microbunching.

The innovative mechanism of steady-state microbunching (SSMB) promises a potent light source, featuring high repetition rate and coherent radiation. The laser modulator, comprising an undulator and an optical enhancement cavity, is pivotal in SSMB. A high-finesse prototype optical enhancement cavity for SSMB with an average power of 55 kW is described in this paper. Preliminary design of the laser modulator, experimental setup, and methods to address frequency degeneracy and power coupling issues are discussed. D-shaped mirrors are utilized to successfully suppress the modal instability. This study is the first to illustrate the finesse reduction caused by high-order mode damping during experiments. The experimental and simulation results match closely. A cavity power coupling model is established, and the experimental results verify the correctness of the coupling model. A method for estimating the absorption coefficient through thermal-induced evolution of cavity mode has been implemented. Experimental results demonstrate a high-average-power enhancement cavity with a finesse of 16 518 ± 103 and an estimated average absorption coefficient of 12 ppm for the cavity mirrors. The findings contribute to the advancement of SSMB by providing insights into the design and operation of high-power optical enhancement cavities.

Development of a thermal diagnostic system for the SPARC tokamak.

The SPARC tokamak will have scrape-off layer parallel heat fluxes on the order of GW/m2. Managing power exhaust of this magnitude will be mandatory for a reactor-scale device. To enable this mission, a thermal diagnostic suite will be deployed to measure the in-vessel structural temperatures to ensure they do not exceed their design limits and to determine the spatial distribution and magnitude of energy deposited onto the first wall. Thermocouples and fiber Bragg gratings have been selected for their environmental compatibility and proven useful on other fusion devices. High-density thermocouple arrays in the divertor will have two spring-loaded thermocouples per divertor target tile, which are being used as calorimeters, and will look to resolve the temperature distribution within the tile due to a swept or static strike point. All systems will need to survive the vacuum vessel bake, set at a minimum plasma facing surface temperature of 350 °C, which presents a particularly challenging environment for the fiber-based subsystem. Along with this temperature design requirement, all the materials in the primary vacuum need to be ultra-high vacuum compatible, able to handle the expected neutron and gamma radiation, as well as tritium exposure, all of which restrict material options. Finally, due to the expected activated environment in SPARC, there will be little chance to replace defective sensors, so system resilience is ensured through toroidal redundancy, probe material selection, and mitigating the impact of common-mode failures. Initial testing of sensors show that intershot structural measurements are sufficiently captured with the raw output, but intrashot measurements of the plasma facing material requires model-based interpretive tools.

Development of the neutral gas diagnostic system for neutral pressure measurements and gas analysis on the SPARC tokamak.

A suite of plasma diagnostics will be installed on the SPARC tokamak to allow for real-time plasma control, an investigation of high-field tokamak physics, and to de-risk the design of ARC, a compact fusion power plant with the aim to supply electricity to the grid. Among these diagnostics is the neutral gas diagnostics system (NTGS), a set of pressure sensors and gas analyzers used to monitor neutral pressure and gas composition for plasma control, optimization of wall conditioning, and helium ash removal, among other measurement functions linked to operational and scientific research needs. While reliable measurements of neutral pressure and gas composition have been fielded on existing magnetic-confinement fusion devices, SPARC represents a step increase in challenge due to its larger power density, higher field, high vacuum vessel bake temperatures, and higher neutron flux environment, as well as a step decrease in the accessibility for maintenance of in-vessel sensors. Multiple sensor types will be employed to have defense-in-depth and mitigate common failure modes. The NTGS system is currently progressing through final design, working to close out decisions using prototyping and analysis, and then moving on to procuring sensors for assembly and installation on SPARC. This paper outlines the current status of the system design and the diagnostic requirements that motivate neutral gas measurements on SPARC, as well as highlights the planned prototyping activities.

[Call attention to the reproductive disorders of chronic endometritis].

Chronic endometritis (CE) is an important factor leading to decreased endometrial receptivity, infertility, and repeated pregnancy loss; endometrial immune dysfunction, abnormal microbial flora, inflammatory status, and other factors play important roles in the occurrence and development of CE. Meanwhile, these factors are closely related to the pathophysiological mechanisms of common diseases that cause infertility, such as endometriosis, polycystic ovary syndrome, tubal diseases, and endometrial polyps. Through further development of high-quality prospective clinical research, microbiome and immunomics of CE and endometriosis,polycystic ovary syndrome and other diseases, to provide a new therapeutic idea for the treatment of refractory CE. In the course of clinical practice, the effective integration of the diagnosis and treatment principles of CE concomitant diseases in the treatment of CE is expected to provide a new choice for preventing the recurrence of CE.

[Biological characteristics of triple negative breast cancer with low expression of HER2].

Objective: To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low). Methods: A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups. Results: Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different (P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions: There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

Inherent uncertainty in pedestrian collision reconstruction: How evidence variability affects head kinematics and injury prediction.

Reconstructing individual cases from real-world collision data is used as a tool to better understand injury biomechanics and determine injury thresholds. However, real-world data tends to have inherent uncertainty within parameters, such as ranges of impact speed, pre-impact pedestrian stance or pedestrian anthropometric characteristics. The implications of this input parameter uncertainty on the conclusions made from case reconstruction about injury biomechanics and risk is not well investigated, with a 'best-fit' approach more frequently adopted, leaving uncertainty unexplored. This study explores the implications of uncertain parameters in real-world data on the biomechanical kinematic metrics related to head injury risk in reconstructed real-world pedestrian-car collisions. We selected six pedestrian-car cases involving seven pedestrians from the highly detailed GB Road Accident In-Depth Studies (RAIDS) database. The collisions were reconstructed from the images, damage measurements and dynamics available in RAIDS. For each case, we varied input parameters within uncertain ranges and report the range of head kinematic metrics from each case. This includes variations of reconstructed collision scenarios that fits within the constraints of the available evidence. We used a combination of multibody and finite element modelling in Madymo to test whether the effect of input data uncertainty is the same on the initial head-vehicle and latter head-ground impact phase. Finally, we assessed whether the predicted range of head kinematics correctly predicted the injuries sustained by the pedestrian. Varying the inputs resulted in a range of output head kinematic parameters. Real-world evidence such as CCTV footage enabled predicted simulated values to be further constrained, by ruling out unrealistic scenarios which do not fit the available evidence. We found that input data uncertainty had different implications for the initial head-vehicle and latter head-ground impact phase. There was a narrower distribution of kinematics associated with the head-vehicle impact (initial 400 ms of the collision) than in the latter head-ground impact. The mean head-vehicle kinematics were able to correctly predict the presence or absence of both subdural haematoma (using peak rotational acceleration) and skull vault fracture (using peak contact force) in all pedestrians presented. This study helps increase our understanding of the effects of uncertain parameters on head kinematics in pedestrian-car collision reconstructions. Extending this work to a broad range of pedestrian-vehicle collision reconstructions spanning broad population demographics will improve our understanding of injury mechanisms and risk, leading to more robust design of injury prevention measures.

[Knowledge, attitude and practices of adult vaccine among the staff of vaccination units in Shandong Province].

In order to understand the knowledge, attitude and practice (KAP) of vaccination against influenza, pneumonia, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, and hepatitis B among staff of vaccination units in Shandong Province, a sample survey was conducted among 797 staffs of adult vaccination units in 12 counties (cities and districts) of Shandong Province from August to September 2022. The results showed that the respondents had the highest total score of knowledge and attitude for the COVID-19 vaccine, with the M (Q1, Q3) of 23 (20, 25) and 10 (10, 10), respectively, and had the lowest score of knowledge and attitude for the herpes zoster vaccine, with the M (Q1, Q3) of 19 (15, 22) and 8 (8, 10), respectively. The vaccine-related knowledge point"vaccine applicable population"had the highest score, with the M (Q1,Q3) of 26 (23, 30). The "contraindications/adverse reactions" and "adverse reaction management" had the lowest score, with the M (Q1, Q3) of 24 (20, 29) and 24 (20, 28), respectively. About 89.71% of respondents received one adult vaccine within two years at least. The principal driver for vaccination of 53.58% of recipients was their understanding of vaccines, which was"it was necessary to receive the vaccine". About 66.00% of respondents who had not received any adult vaccine in the past two years had insufficient awareness of the necessity of vaccination and believed that they were in good health and did not need to receive it. In summary, the staff of adult vaccination units in Shandong Province have a poor understanding of the herpes zoster vaccine in terms of vaccines and a relatively poor understanding of"contraindications/adverse reaction and management"in adult vaccination knowledge points.

Development of a bolometry diagnostic for SPARC.

To control and optimize the power of the SPARC tokamak, we require information on the total radiated power of the plasma and its 2D and 3D spatial distribution. The SPARC bolometry diagnostic is being designed and built to measure the radiated power for controlling power balance, investigating the dissipation capabilities of various divertor concepts, and measuring the efficacy of the disruption thermal load mitigation. Proven resistive bolometer sensor technology will be used, with 248 lines of sight integrated into pinhole cameras in 20 different locations. This diversity of views will allow the bolometers to view the core, divertor, and particularly X-points of the plasma with high resolution. 14 of these camera locations are dedicated to 2D equilibrium radiated power, while the remaining six locations are designed to measure 3D radiated energy during disruptions. The bolometer sensor holders, pinhole camera boxes, and cabling have been designed to survive the high neutron flux (but low fluence) and up to 400 °C temperatures seen during operation and vacuum bake. The resistive bolometer sensors use Au absorbers with an Al heat conduction layer and C anti-reflective layer. These sensor chips are wire-bonded to an AlN circuit board, both of which are held inside a custom AlN and stainless steel bolometer holder. Design and optimization of the pinhole camera lines of sight are performed using Cherab. This work details the current state of the design of the SPARC bolometry diagnostic and its interfaces, as well as ongoing work to validate the design.

[Clinical characteristics analysis of heterotopic cervical pregnancy].

Objective: To investigate the clinical characteristics of heterotopic cervical pregnancy (HCP). Methods: A retrospective analysis was conducted based on the general clinical data, assisted reproductive technology (ART) data, diagnosis and treatment data, and pregnancy outcomes of 17 patients diagnosed with HCP who received ART at the Reproductive Medicine Center of Peking University Third Hospital from January 2011 to April 2022. Results: The age of 17 HCP patients was (34.2±1.5) years, all of whom occurred after the application of ART; Among them, 11 cases had a history of uterine cavity operation. All 17 patients had vaginal bleeding, with only 1 case accompanied by abdominal pain. The gestational age at the diagnosis of HCP was [6+2 (5+2-6+4)] weeks. Two patients underwent conservative observation and were closely followed up. Both of them had intrauterine pregnancy until full-term and underwent cesarean section; One patient underwent ultrasound-guided cervical pregnancy reduction surgery, resulting in miscarriage due to premature rupture of membranes at 18+1 weeks of intrauterine pregnancy; One patient underwent ultrasound-guided cervical pregnancy reduction surgery, followed by uterine artery embolization, hysteroscopy, removal of cervical pregnancy lesions, and curettage due to excessive bleeding; One patient underwent uterine artery embolization, hysteroscopy, cervical pregnancy lesion clearance, and curettage due to excessive vaginal bleeding; One patient underwent hysteroscopy examination, cervical pregnancy lesion removal surgery, and uterine curettage due to embryo arrest during intrauterine pregnancy; 11 cases underwent ultrasound-guided cervical pregnancy lesion clearance surgery, all of which resulted in live births. Among the 13 delivery patients, 4 cases were premature and 9 cases were full-term; 5 cases of vaginal delivery and 8 cases of cesarean section. Conclusions: The most common clinical manifestation of HCP is vaginal bleeding. Ultrasound guided cervical pregnancy lesion clearance surgery is safe and feasible, and with good pregnancy outcomes.

Construction and validation of a prediction model for preoperative prediction of Ki-67 expression in endometrial cancer patients by apparent diffusion coefficient.

AIM: Ki-67 is a marker of cell proliferation and is increasingly being used as a primary outcome measure in preoperative window studies of endometrial cancer (EC). This study explored the feasibility of using apparent diffusion coefficient (ADC) values in noninvasive prediction of Ki-67 expression levels in EC patients before surgery, and constructs a nomogram by combining clinical data. MATERIAL AND METHODS: This study retrospectively analyzed 280 EC patients who underwent preoperative magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in our hospital from January 2017 to February 2023. Evaluate the potential nonlinear relationship between ADC values and Ki-67 expression using the nomogram. The included patients were randomized into a training set (n = 186) and a validation set (n = 84). Using a combination of logistic regression and LASSO regression results, from which the four best predictors were identified for the construction of the nomogram. The accuracy and clinical applicability of the nomogram were assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The results of this study showed a nonlinear correlation between ADCmin and Ki-67 expression (nonlinear P = 0.019), and the nonlinear correlation between ADCmean and Ki-67 expression (nonlinear P = 0.019). In addition, this study constructed the nomogram by incorporating ADCmax, International Federation of Gynecology and Obstetrics (FIGO), and chemotherapy. The area under the curve (AUC) values of the ROC for nomogram, ADCmax, FIGO, chemotherapy and grade in the training set were 0.783, 0.718, 0.579, 0.636, and 0.654, respectively. In the validation set, the AUC values for nomogram, ADCmax, FIGO, chemotherapy, and grade were 0.820, 0.746, 0.558, 0.542, and 0.738, respectively. In addition, the calibration curves and the DCA curves suggested a better predictive efficacy of the model. CONCLUSION: A nomogram prediction model constructed on the basis of ADCmax values combined with clinical data can be used as an effective method to noninvasively assess Ki-67 expression in EC patients before surgery.

[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

[Interpretation of Chinese guideline for the clinical management of patients with ruptured intracranial aneurysms (2024)].

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurological emergency with high mortality, and even patients receiving optimal medical care may develop long-term disability, which seriously affects their quality of life and increases the heavy medical burden on society and families. To provide comprehensive clinical management advice, the Society of Neurosurgery of the Chinese Medical Association, the Society of the Chinese Stroke Association of the National Medical Center for Neurological Diseases, and the National Clinical Research Center for Neurological Diseases jointly formulate "Chinese Guidelines for the Clinical Management of Patients With Ruptured Intracranial Aneurysms in 2024". The evidence sources are divided into the Chinese population and other populations, using a modular format to provide recommendations, summaries of relevant opinions, and future research directions on epidemiology, clinical imaging diagnosis, prognosis evaluation, treatment strategies and choices, anesthesia management, perioperative care, and recommendations for the management of aSAH in special populations. It provides practical clinical guidance and recommendations for doctors and related professionals.

[Oral submucosal fibrosis induced by active components in areca nut: a network pharmacology-based analysis and validation of the mechanism].

OBJECTIVE: To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis (OSF) and the possible mechanism. METHODS: The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software. The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia (2015), PubChem, Chemical book, and SciFinder databases. The potential active components, core targets, biological functions and signaling pathways affecting OSF were analyzed by network pharmacology. The targets of OSF were obtained by integrating Genecards and KEGG databases. The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine (TCMSP), and the target-compound, compound-TCM, target-compound-TCM network was constructed. Molecular docking was used to analyze the component-target binding. Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF. RESULTS: The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways. In the clinical samples, the expressions of PI3K protein decreased and the expressions p-PI3K, AKT1 and PAkt all increased significantly in OSF tissue, where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected. The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals. CONCLUSION: The main active ingredients including arecoline, arecaine, and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia, thus leading to the occurrence of oral submucosal fibrosis.

[Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China].

Objective: To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors. Methods: This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels. Results: Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M (Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) (OR=1.23, 95%CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced (OR=0.68, 95%CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95%CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95%CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95%CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95%CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions: Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.