[Characteristics and Source Analysis of Volatile Organic Compounds in Typical Ozone Pollution Processes During Summer in Jinan, China].

Based on a typical ozone （O3） pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds （VOCs） during different pollution periods （clean period （CP）, pollution rise period （PRP）, heavy pollution period （HPP）, and pollution decline period （PDP）） in the urban area were analyzed. Both positive matrix factorization （PMF） and an observation-based model （OBM） were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρ（O3-8h） during the HPP period in the urban area was （246.67±11.24） µg·m-3, and ρ（O3-1h） had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds （OVOCs）, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential （OFP）. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals （HO2·ï¼‰ and methyl peroxide radicals （CH3O2·ï¼‰ with NO, and the net ozone generation rate during the HPP phase [P（O3）net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.

Association of Lung Cancer Risk With the Presence of Both Lung Nodules and Emphysema in a Lung Cancer Screening Trial.

Background: The coexistence of emphysema and lung nodules could interact with each other and then lead to potential higher lung cancer risk. The study aimed to explore the association between emphysema combined with lung nodules and lung cancer risk. Methods: A total of 21,949 participants from the National Lung Screening Trial (NLST) who underwent low-dose computed tomography (LDCT) examination were included. Participants were categorized into four groups (NENN group (non-emphysema and non-nodules), E group (emphysema without nodules), N group (nodules without emphysema), and E + N group (nodules with emphysema)) according to whether there were lung nodules and emphysema. Multivariable Cox regression and stratified analyses were performed to estimate the association between the four groups and lung cancer risk. Results: Among the 21,949 participants, there were 9,040 (41.2%), 5,819 (26.5%), 4,737 (21.6%), and 2,353 (10.7%) participants in the NENN group, E group, N group, and E + N group. The risk of lung cancer incidence increased in turn in NENN group, E group, N group and E + N group. Compared with NENN group, the age-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of lung cancer incidence were 2.07 (1.69 - 2.54) for E group, 4.13 (3.47 - 5.05) for N group, and 6.26 (5.14 - 7.62) for E + N group. The association was robust to adjustment for potential confounders (1.83 (1.47 - 2.27) for E group, 3.97 (3.24 - 4.86) for N group, and 5.23 (4.28 - 6.48) for E + N group). Comparable results as the lung cancer incidence were observed for lung cancer mortality, whether in age-adjusted model (E group: 1.85 (1.39 - 2.46), N group: 2.49 (1.89 - 3.29), E + N group: 4.27 (3.21 - 5.68)) or fully adjusted model (E group: 1.56 (1.15 - 2.11), N group: 2.43 (1.81 - 3.26), E + N group: 3.39 (2.50 - 4.61)). However, the trend of all-cause mortality risk among the four groups was somewhat different from that of lung cancer risk, whether in age-adjusted model (1.37 (1.21 - 1.54) for E group, 1.06 (0.92 - 1.21) for N group, and 1.75 (1.51 - 2.02) for E + N group) or fully adjusted model (1.26 (1.10 - 1.44) for E group, 1.09 (0.94 - 1.27) for N group, and 1.52 (1.30 - 1.79) for E + N group). Conclusion: Based on a large-scale lung cancer screening trial in the United States, this study demonstrated that either emphysema or lung nodules can increase lung cancer risk, and lung nodules combined with emphysema can further increase the lung cancer risk and all-cause mortality. The significance of these findings for lung cancer screening should be evaluated.

Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.

Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB.

Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent studies have indicated the activation of Sigma-1 receptor plays an important role in providing neuroprotection, especially in ALS and Alzheimer's disease. Nevertheless, the mechanisms underlying Sigma-1R activation and its effect on (G4C2)n-RNA-induced cell death remain unclear. In this study, we demonstrated that fluvoxamine is a Sigma-1R agonist that can increase chaperone activity and stabilize the protein expression of Pom121 in (G4C2)31-RNA-expressing NSC34 cells, leading to increased colocalization at the nuclear envelope. Interestingly, fluvoxamine treatment increased Pom121 protein expression without affecting transcription. In C9orf72-ALS, the nuclear translocation of TFEB autophagy factor decreased owing to nucleocytoplasmic transport defects. Our results showed that pretreatment of NSC34 cells with fluvoxamine promoted the shuttling of TFEB into the nucleus and elevated the expression of LC3-II compared to the overexpression of (G4C2)31-RNA alone. Additionally, even when used alone, fluvoxamine increases Pom121 expression and TFEB translocation. To summarize, fluvoxamine may act as a promising repurposed medicine for patients with C9orf72-ALS, as it stabilizes the nucleoporin Pom121 and promotes the translocation of TFEB in (G4C2)31-RNA-expressing NSC34 cells.

Noninvasive carotid ultrasound for predicting vulnerable plaques of the coronary artery based on optical coherence tomography images.

Background: The risk factors for coronary and carotid plaque development are consistent. Coronary plaque rupture is a major cause of adverse cardiovascular events. Ultrasound can evaluate vulnerable carotid plaques and provide information for predicting vulnerable coronary plaques identified by optical coherence tomography (OCT). This study aimed to investigate the predictive role of non-invasive carotid ultrasound in OCT diagnosis of atherosclerotic vulnerable plaque. Methods: A total of 70 participants, including 35 patients with and 35 without vulnerable coronary plaque, were enrolled in this case-control study at Beijing Anzhen Hospital from 2016 to 2021. The data of 70 patients with suspected coronary heart disease who had undergone OCT examination during percutaneous coronary intervention (PCI) surgery and completed carotid ultrasound examination within 3 days before PCI were analyzed retrospectively. According to the OCT diagnostic criteria for vulnerable plaques, the patients were divided into the vulnerable-plaque group and the stable-plaque group. Univariate and binary logistic regression analyses assessed risk factors for vulnerable coronary plaque. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive power of carotid plaque features. Results: The univariate analysis demonstrated that the differences in high-sensitivity C-reactive protein levels and carotid plaque characteristics (irregular fibrous cap, heterogeneous plaque, hypoechoic plaque, plaque calcification, and a plaque thickness of greater than 3 mm) between the two groups were statistically significant. The logistic multivariate regression analysis revealed that an irregular fibrous cap of a carotid plaque [odds ratio (OR) =4.819; 95% confidence interval (CI): 1.106-22.867; P=0.048] and a hypoechoic plaque (OR =9.632; 95% CI: 2.138-43.384; P<0.05) were independent risk factors for predicting vulnerable plaques of the coronary artery. Conclusions: Noninvasive carotid ultrasound is feasible and clinically valuable for predicting vulnerable and asymptomatic coronary plaques defined by OCT. With this method, adverse events can be diagnosed and treated in advance.

Enhanced skin neocollagenesis through the transdermal delivery of poly-L-lactic acid microparticles by using a needle-free supersonic atomizer.

In this study, a spindle-type nozzle was designed to accelerate poly-L-lactic acid (PLLA) microparticles to supersonic velocities for the transdermal delivery of these microparticles to rats. This approach is needle- and pain-free and enhances skin collagen regeneration. The addition of PLLA microparticles at a concentration of 2 mg/mL did not hinder the growth of 3 T3 fibroblasts and Raw264.7 macrophages. The TNF-α assay revealed no obvious inflammation effect of PLLA microparticles at a concentration of 1 mg/mL. A time-lapse recording revealed that after being cocultured with PLLA microparticles for 24 h, Raw264.7 macrophages gradually approached and surrounded the PLLA microparticles. When 3 T3 fibroblasts were cocultured with Raw264.7 macrophages, which were stimulated using PLLA microparticles, collagen synthesis was increased by approximately 60 % compared with that in samples without PLLA microparticles. In vivo animal experiments indicated that after the transdermal delivery of 10 shots of PLLA microparticles through the supersonic atomizer, no obvious changes or damage to the back skin of Sprague-Dawley rats was observed. More importantly, numerous PLLA microparticles penetrated the rat epidermis into the dermal layer. We found macrophages and fibroblasts present close to the PLLA microparticles. Moreover, only mild or no inflammation reaction was observed. Masson staining revealed that after 6-week implantation, 6 % and 12 % of PLLA microparticles significantly stimulated collagen regeneration in 6-week-old and 32-week-old rats. In addition, picrosirius red staining revealed a significant increase in collagen regeneration, especially for type III collagen, following the 6-week implantation of PLLA microparticles. In summary, this study demonstrated an easy, pain-free, nondestructive approach for introducing PLLA microparticles into the dermal layer by using a supersonic atomizer to stimulate collagen regeneration in vivo.

A high-gain dual-band shared-aperture array integrating zero-order-resonance patch and higher-order metasurface antenna.

This letter proposes a high-gain shared-aperture array for vehicular communications which integrates the hybrid zeroth-order-resonance (ZOR) patch and the higher-order metasurface antenna (MA). In terms of each array element, four hybrid ZOR patches with shorting pins form a metasurface which is fed by slot coupling. Different from some reported designs which have more high-frequency elements than low-frequency ones, the whole array is composed of 4 [Formula: see text] 4 hybrid ZOR patches operating in C band (4.74-5.12 GHz) and 2 [Formula: see text] 2 MAs working in Ku band (13.0-14.0 GHz). Such a layout brings that the designed array has the benefit to reduce Ku-band loss. Measure results validate the dual-band operation and show that the antenna has its peak gains of 12.7 dBi and 17.2 dBi in these two bands, respectively, which can support vehicle-to-base station and vehicle-to-satellite communications.

Peer victimization and adolescent problematic social media use: The mediating role of psychological insecurity and the moderating role of family support.

Peer victimization is a serious risk factor for the development of problematic social media use (PSMU) among adolescents. However, little is known about the mediating and moderating mechanisms underlying this association. The current study tested whether psychological insecurity mediated the relation between peer victimization and PSMU, and whether this mediating process was moderated by family support among adolescents. A large sample of 1506 Chinese adolescents (Mage = 13.74 years, SD = 0.98) completed self-report measures regarding peer victimization, psychological insecurity, family support, and PSMU. After controlling for age, gender, and family economic status, results indicated that increased peer victimization was associated with higher psychological insecurity, which in turn predicted a greater incidence of PSMU. Moreover, family support moderated the first part of the mediation process, such that the relation between peer victimization and psychological insecurity was exacerbated for adolescents with high family support. This study advanced the current understanding of the mediating and moderating mechanisms associating peer victimization with PSMU among adolescents.

Clinical study of carotid superb microvascular imaging in evaluating the activity of Takayasu's arteritis.

Objective: The goal of this study is to use superb microvascular imaging (SMI) to observe neovascularization in the carotid vessel wall to identify potential Takayasu's arteritis (TAK) inflammation markers. Methods: Bilateral carotid arteries from 96 patients with TAK were imaged by a Doppler ultrasound and SMI. The one-way analysis of variance (ANOVA) was used to document significant differences between the activity and inactivity stages of TAK and the factors closely related to its activity in the binary logistics regression equation. Clinical and laboratory data included age, gender, duration of disease, treatment history, NIH score, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein. Imaging data included the arterial wall thickness, degree of lesion, SMI grade, and arterial aneurysm formation. Results: There were 45 patients in the active TAK stage and 51 in the inactive stage. The one-way ANOVA showed significant differences in SMI (p = 0.001) and ESR (p = 0.022) between the active and inactive groups. The binary logistics regression analysis showed that SMI was an independent risk factor for TAK activity (B = -1.505, S.E = 0.340, Wald = 19.528, OR = 0.222 95%, CI = 0.114-0.433, p < 0.01). Using SMI G1 or G2 as the cutoff values for the diagnosis of active TAK, the positive predictive value, sensitivity, and specificity were 60 and 86%, 84% and 56%, and 54% and 92%, respectively. Conclusion: The SMI grade is a potential marker of disease activity in patients with TAK.

Testis and epididymis-unusual sites of metastatic gastric cancer: A case report and review of the literature.

BACKGROUND: Although gastric cancer is one of the most prevalent cancers worldwide, cases of gastric cancer metastasis to the male reproductive system are rare. Here, we report a case involving testicular and epididymal gastric cancer metastases. CASE SUMMARY: A 75-year-old Chinese man complained of experiencing a palpable painful mass in the right scrotum for 6 mo. He had undergone distal gastrectomy with chemotherapy for pT3N3aMx poorly differentiated gastric adenocarcinoma 9 mo before. Physical examination revealed a moderate right hydrocele and a painful mass in the right testis and epididymis. Serum tumor biomarkers were all normal except for elevated beta-human chorionic gonadotropin levels. Computed tomography urography and B-ultrasound imaging revealed a moderate right hydrocele and a mixed solid-cystic mass in the right testicular and epididymal area. Thus, the patient underwent right radical orchiectomy. Immunohistochemical analysis revealed that the tumor cells were positive for pancytokeratins and caudal related homeodomain transcription 2. Metastatic, poorly differentiated gastric adenocarcinoma of the testis and epididymis was confirmed by pathology. He continued to undergo chemotherapy at the department of oncology of our hospital. Mesenteric lymph node metastases were found at the postoperative 1-mo follow-up. CONCLUSION: Palpable, painful scrotal mass, history of gastric cancer, and imaging features may indicate testicular and epididymal metastatic gastric cancer.

Ocular Perfusion Pressure in 7- and 12-Year-Old Chinese Children: The Anyang Childhood Eye Study.

Purpose: The purpose of this study was to report the distribution of mean ocular perfusion pressure (MOPP) and its associated factors in Chinese children. Methods: We enrolled 3048 grade 1 students and 2258 grade 7 students of the Anyang Childhood Eye Study in central China. Systolic and diastolic blood pressure (SBP and DBP) were recorded with a digital automatic sphygmomanometer. Intraocular pressure (IOP) was assessed by a non-contact tonometer. MOPP was calculated as 2/3 × (DBP + 1/3[SBP - DBP]) - IOP. Risk factors for myopia were obtained through a questionnaire survey. Results: The MOPP was 33.83 ± 6.37 mm Hg (mean ± SD) in grade 1, which was lower than 36.99 ± 6.80 mm Hg in grade 7 (P < 0.001). Compared with myopic eyes, non-myopic eyes had higher MOPP in grade 7 (37.72 ± 6.72 mm Hg versus 36.58 ± 6.57 mm Hg, P < 0.001) and in grade 1 (33.88 ± 6.29 mm Hg versus 33.12 ± 7.03 mm Hg, P = 0.12). Multivariable analysis showed that higher MOPP was associated with less myopia (P < 0.001), higher body mass index (BMI; P < 0.001), thinner central corneal thickness (P < 0.001), less time on near work (P < 0.001), and more time on sleeping (P = 0.04). Conclusions: MOPP was higher in children of older age, with higher BMI, less time on near work, and more time on sleeping, and was higher in eyes with less myopia. Translational Relevance: We found that MOPP might be an indicator for the detection of myopia development.

Descriptive peer drinking norms and binge drinking: Enhancement motives as a mediator and alcohol resistance self-efficacy as a moderator.

The association between descriptive norms regarding peer drinking and college students' binge drinking has been established; however, the mediating and moderating mechanisms underlying this relationship among first-and second-year college students remain minimally explored. Drawing on social norms theory, motivational model of alcohol use, and the theory of normative social behavior, the current study investigated whether enhancement drinking motives mediated the relationship between descriptive norms regarding peer drinking and college students' binge drinking, and whether this relationship was moderated by alcohol resistance self-efficacy. Five hundred and nineteen first-and second-year college students (M age = 19.19 years, SD = 0.98) who were from four universities and had at least one time of heavy episodic drinking during the last year completed self-report questionnaires. After controlling for sex, age, and university variable, stronger descriptive norms regarding peer drinking were positively associated with a greater frequency of binge drinking. Enhancement drinking motives partially mediated the effects of descriptive peer drinking norms on binge drinking. Furthermore, alcohol resistance self-efficacy moderated the direct effects of descriptive peer drinking norms on binge drinking. Compared with college students who reported high alcohol resistance self-efficacy, the direct effects of descriptive peer drinking norms on binge drinking were stronger among students with low alcohol resistance self-efficacy. These findings point to the potential value of alcohol intervention approaches including efforts to help first-and second-year college students change enhancement drinking motives and increase their ability of resisting drinks in the context of pervasive peer drinking.

Puerarin: A review of its mechanisms of action and clinical studies in ophthalmology.

BACKGROUND: Pueraria is the common name of the dried root of either Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) or Pueraria montana var. thomsonii (Benth.) M.R.Almeida (syn. Pueraria thomsonii Benth.). Puerarin is a C-glucoside of the isoflavone daidzein extracted from Pueraria. It has been widely investigated to explore its therapeutic role in eye diseases and the molecular mechanisms. PURPOSE: To collect the available literature from 2000 to 2022 on puerarin in the treatment of ocular diseases and suggest the future required directions to improve its medicinal value. METHOD: The content of this review was obtained from databases such as Web of Science, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and the Wanfang Database. RESULTS: The search yielded 428 articles, of which 159 articles were included after excluding duplicate articles and articles related to puerarin but less relevant to the topic of the review. In eleven articles, the bioavailability of puerarin was discussed. Despite puerarin possesses diverse biological activities, its bioavailability on its own is poor. There are 95 articles in which the therapeutic mechanisms of puerarin in ocular diseases was reported. Of these, 54 articles discussed the various signalling pathways related to occular diseases affected by puerarin. The other 41 articles discussed specific biological activities of puerarin. It plays a therapeutic role in ophthalmopathy via regulating nuclear factor kappa-B (NF-ĸB), mitogen-activated protein kinases (MAPKs), PI3K/AKT, JAK/STAT, protein kinase C (PKC) and other related pathways, affecting the expression of tumour necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), superoxide dismutase (SOD), B-cell lymphoma-2 (Bcl-2) and other cytokines resulting in anti-inflammatory, antioxidant and anti-apoptotic effects. The clinical applications of puerarin in ophthalmology were discussed in 25 articles. Eleven articles discussed the toxicity of puerarin. The literature suggests that puerarin has a good curative effect and can be used safely in clinical practice. CONCLUSION: This review has illustrated the diverse applications of puerarin acting on ocular diseases and suggested that puerarin can be used for treating diabetic retinopathy, retinal vascular occlusion, glaucoma and other ocular diseases in the clinic. Some ocular diseases are the result of the combined action of multiple factors, and the effect of puerarin on different factors needs to be further studied to improve a more complete mechanism of action of puerarin. In addition, it is necessary to increase the number of subjects in clinical trials and conduct clinical trials for other ocular diseases. The information presented here will guide future research studies.

Involvement of NO and Ca2+ in the enhancement of cold tolerance induced by melatonin in winter turnip rape (Brassica rapa L.).

As a multifunctional phytohormone, melatonin (Mel) plays pivotal roles in plant responses to multiple stresses. However, its mechanism of action remains elusive. In the present study, we evaluated the role of NO and Ca2+ signaling in Mel enhanced cold tolerance in winter turnip rape. The results showed that the NO content and concentration of intracellular free Ca2+ ([Ca2+]cyt) increased by 35.42% and 30.87%, respectively, in the leaves of rape seedlings exposed to cold stress. Compared with those of the seedlings in cold stress alone, the NO content and concentration of [Ca2+]cyt in rape seedlings pretreated with Mel increased further. In addition, the Mel-mediated improvement of cold tolerance was inhibited by L-NAME (a NO synthase inhibitor), tungstate (a nitrate reductase inhibitor), LaCl3 (a Ca2+ channel blocker), and EGTA (a Ca2+ chelator), and this finding was mainly reflected in the increase in ROS content and the decrease in osmoregulatory capacity, photosynthetic efficiency and antioxidant enzyme activities, and expression levels of antioxidant enzyme genes. These findings suggest that NO and Ca2+ are necessary for Mel to improve cold tolerance and function synergistically downstream of Mel. Notably, the co-treatment of Mel with L-NAME, tungstate, LaCl3, or EGTA also inhibited the Mel-induced expression of MAPK3/6 under cold stress. In conclusion, NO and Ca2+ are involved in the enhancement of cold tolerance induced by Mel through activating the MAPK cascades in rape seedlings, and a crosstalk may exist between NO and Ca2+ signaling.

A unique hub-and-spoke model to optimize patient management in lymphoma using novel CAR-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The CAR-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been at least 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

A unique hub-and-spoke model to optimize patient management in lymphoma using novel chimeric antigen receptor-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The chimeric antigen receptor (CAR)-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been about 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Interaction of genotype-ecological type-plant spacing configuration in sorghum [Sorghum bicolor (L.) Moench] in China.

Grain sorghum has been a significant contributor to global food security since the prehistoric period and may contribute even more to the security of both food and energy in the future. Globally, precise management techniques are crucial for increasing grain sorghum productivity. In China, with diverse ecological types, variety introduction occasionally occurs across ecological zones. However, few information is available on the effect of ecological type on genotype performance and how plant spacing configuration influences grain yield in various ecological zones. Hence, a series of two-year field experiments were conducted in 2020 and 2021 in four ecological zones of China, from the northeast to the southwest. The experiments included six widely adapted sorghum varieties under six plant spacing configurations (two row spacing modes: equidistant row spacing (60 cm) mode and wide (80 cm)-narrow (40 cm) row spacing mode; three in-row plant spacings: 10 cm, 15 cm, and 20 cm). Our results indicated that ecological type, variety, and plant spacing configuration had a significant effect on sorghum yield. Ecological type contributed the highest proportion to the yield variance (49.8%), followed by variety (8.3%), while plant spacing configuration contributed 1.8%. Sorghum growth duration was highly influenced by the ecological type, accounting for 87.2% of its total variance, whereas plant height was mainly affected by genotype, which contributed 81.6% of the total variance. All test varieties, developed in the south or north, can reach maturity within 94-108 d, just before fall sowing in central China. Generally, sorghum growth duration becomes longer when a variety is introduced from south to north. A late-maturing variety, developed in the spring sowing and late-maturing regions, possibly could not reach maturity in the early-maturing region. The row spacing modes had no significant affect on sorghum yield, but the equal-row spacing mode consistently caused higher yields with only one exception; this might imply that equal-row spacing mode was more advantageous for boosting sorghum yield potential. In contrast, decreasing in-row plant spacing showed significant positive linear associations with sorghum grain yield in most cases. In addition, these results demonstrated that sorghum is a widely adapted crop and enables success in variety introduction across ecological zones.

Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable.

Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.

Endu combined with concurrent chemotherapy and radiotherapy for stage IIB-IVA cervical squamous cell carcinoma patients.

BACKGROUND: In recent years, the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles, posing a serious threat to women's physical and mental health. AIM: To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma. METHODS: A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects. They were equally divided into the test group and the control group (60 patients each) with a random number table. The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy, and the control group was treated with concurrent radiotherapy and chemotherapy. We compared the serum thymidine kinase 1 (TK1), human epididymis protein 4 (HE4), vascular endothelial growth factor (VEGF), and squamous cell carcinoma-associated antigen (SCC-Ag) levels, the clinical effects and survival before and after radiotherapy and chemotherapy, the quality score, and the 3-year follow-up outcomes between the two groups. RESULTS: After chemotherapy, the complete remission + partial remission rate was 85.00% in the test group and 68.33% in the control group; the difference was not statistically significant (P > 0.05). Before chemotherapy, the serum TK1, HE4, VEGF, and SCC-Ag levels of the two groups were not significantly different (P > 0.05). After chemotherapy, the levels of serum TK1 (1.27 ± 0.40 pmol/L), HE4 (81.4 ± 24.0 pmol/L), VEGF (235.1 ± 38.0 pg/mL), and SCC-Ag (1.76 ± 0.55 ng/mL) were lower than those in the control group [TK1 (1.58 ± 0.51 pmol/L), HE4 (98.0 ± 28.6) pmol/L, VEGF (284.2 ± 54.1 pg/mL), and SCC-Ag (2.34 ± 0.78 ng/mL)]. The difference was statistically significant (P < 0.05). Before chemotherapy, there were no significant differences in the physical, role, mood, cognition, social and symptom scale scores of the two groups (P > 0.05). After chemotherapy, the physical, role, mood, cognitive and social scores were higher in the test group than in the control group, and the difference was statistically significant (P < 0.05). The symptom scale scores of the test group were all lower than those of the control group, and the difference was statistically significant (P < 0.05). The 3-year progression-free survival (PFS) rate was 43.33% in the test group and 26.67% in the control group; the overall survival (OS) rate was 48.33% in the test group and 33.33% in the control group; the differences were not statistically significant (P > 0.05). The 3-year PFS time of the test group was 20.0 mo, which was longer than that of the control group (15.0 mo), and the difference was significant (P < 0.05). The OS time of the test group was 30.0 mo, which was longer than that of the control group (18.0 mo), and the difference was significant (P < 0.05). CONCLUSION: Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients, prolonging the PFS and OS times of patients, and improving the quality of life.