Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Analysis of current state, gaps, and opportunities for technologies in the Malaysian oil palm estates and palm oil mills towards net-zero emissions.

Malaysia is the second largest producer and exporter of palm oil. Though several works have explored achieving emissions reduction in the palm oil sector, there existing gaps in analysing pathways for achieving net-zero emissions. Moreover, there are limited studies that evaluate the potential of palm oil biomass utilisation pathways based on emissions reduction capabilities, the cost of emissions reduction, and the technology readiness for implementation. Therefore, this study analysed decarbonisation pathways for the upstream and midstream segments of the palm oil sector in Malaysia, encompassing oil palm plantations and palm oil mills. Various sources of greenhouse gas emissions in oil palm plantations and palm oil mills were identified and estimates of emissions were determined as theoretical emissions. The current emissions were established based on the current best practice in the plantation and mill. Several biomass conversion technologies for the recovery of palm-based by-products and conversion into value-added products to decarbonise the palm oil sector and evaluated strategies to attain net-zero status are considered. In this work, the analysis considered both the existing technologies that are adopted by plantations and mills as well as the emerging technologies that have scope for implementation. With the proposed approach, the current emissions level for crude palm oil (CPO) production in Malaysia is estimated as 1121.49 kg CO2-eq/t CPO. In current industry practice, empty fruit bunch (EFB) is underutilised as mills are typically located at rural areas with lack of suitable transportation. Besides, the lack of accessibility to the grid also limits the potential of converting EFB into electricity as supply for national grid. This work examined various pathways for EFB utilisation under different scenarios evaluating their contribution potential towards net-zero target in an energy self-sustained CPO production. As shown in the results, converting EFB to briquettes and pellets are able to achieve the net-zero objective. Furthermore, EFB-biochar and EFB-syngas pathways also exhibit the potential to accomplish the net-zero target. Note that this work also assessed the technologies' readiness levels, identified challenges in implementation, and proposed several recommendations.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Quality of life in patients with nasopharyngeal carcinoma receiving IMRT vs IMPT: a multicenter prospective longitudinal study.

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.

Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy.

BACKGROUND: Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. PURPOSE: This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. METHODS: One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain Inventory-Short Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. RESULTS: Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians.

An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy.

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, 'TOPAS,' and an image registration toolbox, 'Elastix,' to calculate 4D dose distributions from 5 patients' four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn't significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2-3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.

Effects of a return to work program on the health and barriers to returning to work in head and neck cancer patients: A randomized controlled trial.

Objective: The aim of the study was to evaluate the effects of a return to work (RTW) program on perceived health status, barriers to returning to work, fear of cancer progression, social support, physical function, and psychosocial function in head and neck cancer (HNC) patients. Methods: A randomized controlled trial with repeated measures was conducted. The 70 HNC patients were randomly assigned into two groups: 35 in the experimental group (RTW) and 35 in the control group (usual care). Patients were assessed at four time points: baseline (T0) (6 months after completing treatment), and then at 9-, 12-, and 15-months (T1, T2, and T3, respectively) after completing treatment. Patients completed a self-reported questionnaire, including measures of perceived health status, barriers to returning to work, fear of cancer progression, social support, physical function, and psychosocial function. Results: Patients in the experimental group had significantly greater perceived health status and better psychosocial function compared to those in the control group. Compared to T0, at T4, participants in both groups had significantly lower levels of barriers to returning to work, fear of cancer progression, social support, and higher levels of physical function. Conclusions: The RTW program effectively improved perceived health status and psychosocial function in HNC patients. Survivorship care should include a transitional return-to-work program to help patients transition back to work. Trial registration: NCT04322695.

Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Vertebral artery sparing volumetric modulated arc therapy in nasopharyngeal carcinoma.

Vascular stenosis is a late radiation complication that develops in long-term survivors of nasopharyngeal carcinoma. Vertebral arteries (VAs) are major vessels responsible for posterior circulation. In this study, we evaluated the feasibility of VA-sparing volumetric modulated arc therapy (VMAT) techniques. A total of 20 patients with nasopharyngeal carcinoma treated by a TrueBeam linear accelerator were enrolled in this study. The original VMAT plan was designed without the contouring of VAs as organs at risk (OARs). The same image set of the original VMAT plan was used to contour the VAs for each patient. A new VA-sparing VMAT plan was developed by avoiding VAs as OARs. Finally, a paired t-test was used to compare the dosimetric differences. The VA-sparing VMAT plan had similar target coverage and dose to those of other OARs. The VA-sparing plan yielded a significantly low VA dose from 53 to 40 Gy, with V35Gy changing from 97% to 56%, V50Gy changing from 67% to 35%, and V63Gy changing from 15% to approximately 7%-10% (p < 0.001 for all comparisons). VAs should be correctly identified as OARs. Photon VMAT with VA sparing can help substantially decrease the VA dose.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers.

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Smart solutions for clean air: An AI-guided approach to sustainable industrial pollution control in coal-fired power plant.

Conventional fossil fuels are relied on heavily to meet the ever-increasing demand for energy required by human activities. However, their usage generates significant air pollutant emissions, such as NOx, SOx, and particulate matter. As a result, a complete air pollutant control system is necessary. However, the intensive operation of such systems is expected to cause deterioration and reduce their efficiency. Therefore, this study evaluates the current air pollutant control configuration of a coal-powered plant and proposes an upgraded system. Using a year-long dataset of air pollutants collected at 30-min intervals from the plant's telemonitoring system, untreated flue gas was reconstructed with a variational autoencoder. Subsequently, a superstructure model with various technology options for treating NOx, SOx, and particulate matter was developed. The most sustainable configuration, which included reburning, desulfurization with seawater, and dry electrostatic precipitator, was identified using an artificial intelligence (AI) model to meet economic, environmental, and reliability targets. Finally, the proposed system was evaluated using a Monte Carlo simulation to assess various scenarios with tightened discharge limits. The untreated flue gas was then evaluated using the most sustainable air pollutant control configuration, which demonstrated a total annual cost, environmental quality index, and reliability indices of 44.1 × 106 USD/year, 0.67, and 0.87, respectively.

Rethinking of the future sustainable paradigm roadmap for plastic waste management: A multi-nation scale outlook compendium.

The myriad consumption of plastic regularly, environmental impact and health disquietude of humans are at high risk. Along the line, international cooperation on a global scale is epitomized to mitigate the environmental threats from plastic usage, not limited to implementing international cooperation strategies and policies. Here, this study aims to provide explicit insight into possible cooperation strategies between countries on the post-treatment and management of plastic. First, a thorough cradle-to-grave assessment in terms of economic, environmental, and energy requirements is conducted on the entire life cycle across different types of plastic polymers in 6 main countries, namely the United States of America, China, Germany, Japan, South Korea, and Malaysia. Subsequently, P-graph is introduced to identify the integrative plastic waste treatment scheme that minimizes the economic, environmental, and energy criteria (1000 sets of solutions are found). Furthermore, TOPSIS analysis is also being adapted to search for a propitious solution with optimal balance between the dominant configuration of economic, environmental, and energy nexus. The most sustainable configuration (i.e., integrated downcycle and reuse routes in a closed loop system except in South Korea, which proposed another alternative to treat the plastic waste using landfill given the cheaper cost) is reported with 4.08 × 108 USD/yr, 1.76× 108 kg CO2/yr, and 2.73 × 109 MJ/yr respectively. To attain a high precision result, Monte-Carlo simulation is introduced (10,000 attempts) to search for possible uncertainties, and lastly, a potential global plastic waste management scheme is proposed via the PESTLE approach.

Effects of a Nurse-led Survivorship Care Program on the Health and Resilience of Primary Caregivers of Patients With Advanced Head and Neck Cancer: A Randomized Controlled Trial.

OBJECTIVES: The present study aimed to evaluate the effects of a nurse-led survivorship care program (SCP) on emotional distress, social support, physical health, mental health, and resilience in primary caregivers of patients with advanced head and neck cancer. DATA SOURCES: A randomized controlled trial was conducted. One hundred patient-primary caregiver dyads were randomized into the nurse-led SCP group (experimental) or the usual care group (control). Participants completed a self-reported questionnaire, including measures of emotional distress, social support, physical health, mental health, and resilience. After 6 months, the experimental group reported a significant improvement in emotional distress, social support, physical health, mental health, and resilience. Compared with the control group, measures of emotional distress, physical health, overall resilience, and the resilience aspects of equanimity and perseverance improved in the experimental group. CONCLUSION: An SCP may feasibly help alleviate emotional distress, improve social support, increase physical and mental health, and strengthen resilience in the primary caregivers of patients with head and neck cancer. Health care providers should encourage primary caregivers to join an SCP. IMPLICATIONS FOR NURSING PRACTICE: The nurse-led SCP can be applied before patients complete treatment, which may increase the positive effect on physical health and adaptation.

Combination of Lenvatinib and Proton Beam Therapy in the Management of Patients With Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: This retrospective study was designed to investigate the efficacy and safety of concurrent lenvatinib and proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients. PATIENTS AND METHODS: Twenty HCC patients were identified, including Child-Pugh classification A in 16 patients and B (7) in four patients. Sixteen patients had macrovascular invasion, including four with main portal vein thrombosis (Vp4). The dose of lenvatinib depends on body weight; the median PBT dose was 72.6 Gy. RESULTS: The median progression-fee survival (PFS) and overall survival (OS) of the entire population were 8.3 months and 18.4 months, respectively. For PBT targeting intrahepatic lesions and great vessels, the objective response rate (ORR) showed a complete response and partial response (PR) of 20% and 65%, respectively. In the analysis of concurrent lenvatinib and PBT, the ORR included PR of 55% and stable disease of 25%, with disease control rate of 80%. For patients without distant metastasis upon treatment initiation, the time to local control failure (including proton in-field and out-field) was 14.3 months and distant metastasis-free survival was 17.7 months. There was no statistical difference in the analysis of PFS and OS in patients with or without portal vein thrombosis. The severity of most adverse events was grades 1-2, wherein most patients tolerated the toxicities. CONCLUSION: Our study confirmed the efficacy and safety of concurrent lenvatinib and PBT. Thus, this combination therapy may be a reasonable treatment option for selected patients with advanced HCC in clinical practice.

Factors Facilitating or Creating Barriers to Returning to Work in Head and Neck Cancer Patients Within the First 6 Months After Treatment.

Head and neck cancer (HNC) patients who are unable to return to work after completing treatment might face financial loss and reduced self-esteem. The aim of this study was to identify factors influencing a return to work in HNC cancer patients in the first 6 months after treatment. This cross-sectional study examined HNC patients who completed treatment from the outpatient radiation department of a single cancer center in northern Taiwan. Patients were assessed according to psychological distress, patient-perceived health status, barriers to returning to work, and facilitators of returning to work. Of the 106 HNC patients surveyed, 54.7% successfully returned to work. Barriers to returning to work included poor self-perception of health, greater psychological distress, and age ≥50 years. Patients who had higher psychological distress, returned to work after start of the pandemic, or received reconstruction surgery were less likely to experience a positive environment facilitating a return to work.

Post-irradiation sarcoma after definitive radiation therapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Postirradiation sarcoma (PIS) is a rare radiation-induced malignancy after nasopharyngeal carcinoma (NPC) treatment. MATERIALS AND METHODS: We retrospectively screened 9,185 NPC patients between 2000 and 2020 and identified 41 patients with PIS according to the modified Cahan's criteria: (1) the PIS must have arisen within a previous radiation field; (2) a latent period must have existed; (3) histologically proved sarcoma; (4) the tissue in which the PIS arose must have been healthy prior to the radiation. The initial radiation therapy techniques used were 2D (25; 61.0%), 3D (7; 17.1%), and IMRT (9; 22%). RESULTS: The time (year) from radiotherapy (RT) to PIS was longer when using 2D or 3D irradiation techniques (median, 14.2; range, 3.4-28.1; Q1-Q3, 8.6-19.7) than when using IMRT (median, 6.6; range, 3.8-15.7; Q1-Q3, 4.5-11.7; P =.026). The time (year) from RT to PIS diagnosis was significantly longer when using lower radiation energy from cobalt-60 (median, 15.8; range, 10.4-28.4; Q1-Q3, 12.5-23.8) than when using a higher radiation energy of 6 or 10 MV (median, 10.2; range, 3.4-23.3; Q1-Q3, 6.5-16.1; P =.006). The 2-year overall survival rates for patients who underwent surgery, radical radiotherapy, systemic therapy alone and no treatment were 60.7 %, 42.9 %, 0 % and 0 %, respectively (P =.000). Of the 3 retrievable initial RT dosimetry plans for NPC, the D95 values (dose that covers 95 % of the PIS volume) for PIS were 6267, 6344 and 5820 cGy, respectively. CONCLUSION: High radiation energy and modern techniques may shorten NPC PIS latency. Surgery may be associated with improved survival if feasible.

Role of PHB2 in mitochondrial calcium dynamics and mitophagy / 中国药理学与毒理学杂志

OBJECTIVE Mitochondria plays a crucial role in cellular homeostasis by regulating various pro-cesses,including calcium signaling and mitophagy.This study aimed to explore the involvement of prohibitin 2(PHB2),an inner mitochondrial membrane protein,in the modulation of mitochondrial calcium dynamics and mitoph-agy.METHODS HEK293T cells were used as the experi-mental cells and were divided into control,PHB2 knock-down,and PHB2 overexpression groups.To evaluate mitochondrial calcium dynamics,Rhod-2 AM and Mito-Tracker Green fluorescence dyesrhod-2 staining and laser confocal microscopy were employed to visualize mito-chondrial calcium imaging.Additionally,Green-5N was utilized to measure the rate of mitochondrial calcium uptake.The mitochondrial membrane potential was assessed using JC-10 staining and laser confocal micros-copy,while cellular ATP levels were determined using ATP assay kits.Furthermore,mitochondrial autophagy was induced by treatment with CCCP,and the expression lev-els of TOM20,LC3,and PARKIN,key mitophagy-related proteins,were analyzed using Western blotting.RESULTS The results demonstrated that compared to the control group,the overexpression of PHB2 increased mitochon-drial calcium concentration,mitochondrial calcium uptake rate,ATP level and expression levels of LC3 and PAR-KIN,but decreased mitochondrial membrane potential and TOM20 expression.In contrast,PHB2 knockdown reduced mitochondrial calcium concentration,ATP level and expression levels of LC3 and PARKIN,but elevated mitochondrial membrane potential,and TOM20 expres-sion.CONCLUSION This study provides evidence that PHB2 plays a vital role in regulating mitochondrial calci-um dynamics,which in turn influences mitochondrial func-tion and modulates mitochondrial autophagy.These find-ings contribute to our understanding of the molecular mechanisms underlying the interplay between PHB2,mitochondrial calcium signaling,and mitophagy.

Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Selective inhibition of inflammatory cytokine storm in macrophages by α-momorcharin / 中国药理学通报

Aim To observe the inhibitory effect of Alpha-momorcharin (α-MMC) on the inflammatory cytokine storm of Ml-type inflammatory macrophages induced by LPS and explore its possible targeting mechanism. Methods Western blot was used to detect the expression of WIL2-S B lymphocytes, H9 T lymphocytes, THP-1 monocytes and M0 macrophages LRP1 receptor protein. CCK-8 method was used to detect the survival rate of the four cells. ELISA was used to detect the expression level of inflammatory cytokines in Ml macrophages. Western blot was used to detect the expression of TLR4 signaling pathway-related protein in Ml macrophages. Results Macrophages had a high density of LRP1 receptors consistent with monocytes; the survival rate of α-MMC on the four cells was positively correlated with the density of this receptor; α-MMC inhibited the expression of inflammatory cytokinesTNF-α, IL-lβ, IL-6, IL-8, MlP-lα and MCP-1 in Ml macrophages in a dose-and time-dependent manner; α-MMC showed significant inhibition to TAKl/pTAK1, p-JNK, p-APl and p-p65 signaling proteins of the TLR4 signaling pathway, and this inhibition could be blocked by the LRP1 receptor blocker RAP. Conclusions α-MMC selectively inhibits macrophage inflammatory cytokine synthesis by inhibiting TAK1 of the TLR4 signaling pathway, which in turn inhibits the downstream NF-ΚB and MAPK pathways, mediated by the LRP1 receptor. The selective immunosuppressive effect of α-MMC on macrophages may make it a very promising agent for the treatment of acute infectious macrophage activation syndrome (MAS).

Multi-omics approaches for revealing the etiology of cancer: from genomics, exposomics, metabolomics to system epidemiology / 中华流行病学杂志

Identifying risk factors of the disease are one of the main tasks of epidemiology. With the advancement of omics technologies (e.g., genome, transcriptome, proteome, metabolome, and exposome), cancer etiology research has entered the stage of systems epidemiology. Genomic research identifies cancer susceptibility loci and uncovers their biological mechanisms. Exposomic research investigates the impact of environmental factors on biological processes and disease risks. The metabolome is downstream of biological regulatory networks, reflecting the effects of the gene, environment, and their interactions, which can help elucidate the biological mechanisms of genetic and environmental risk factors and identify new biomarkers. Here, we reviewed the applications of genomic, exposomic, and metabolomic studies in the etiologic research on cancer. We summarized the importance of multi-omics approaches and systems epidemiology in cancer etiology research and outlined future perspectives.