Postoperative radiotherapy with docetaxel versus cisplatin for high-risk oral squamous cell carcinoma: a randomized phase II trial with exploratory analysis of ITGB1 as a potential predictive biomarker.

BACKGROUND: Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). METHODS: In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III-IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin ß1 (ITGB1) expression was analyzed as a biomarker for efficacy. RESULTS: After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. CONCLUSIONS: This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . NCT02923258 (date of registration: October 4, 2016).

Adiposity modifies the association between heart failure risk and glucose metabolic disorder in older individuals: a community-based prospective cohort study.

BACKGROUND: Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear. METHODS: A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period. RESULTS: A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, Padj.=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, Padj.<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, Padj.=0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all Padj.<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all Padj.<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all Padj.<0.05). CONCLUSIONS: Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF. TRIAL REGISTRATION: retrospectively registered number: ChiCTR-EOC-17,013,598.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia.

BACKGROUND: Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. METHODS: The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. RESULTS: There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. CONCLUSIONS: At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. TRIAL REGISTRATION: The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

Integrated Metabolome and Transcriptome Analysis Reveals a Potential Mechanism for Water Accumulation Mediated Translucency in Pineapple (Ananas comosus (L.) Merr.) Fruit.

A physiological disease of the pineapple fruit called pineapple translucency causes the pulp to become water-soaked, which affects the fruit's taste, flavor, shelf life, and integrity. In the present study, we analyzed seven pineapple varieties, of which three were watery and four were non-watery. There were no apparent macronutritional (K, P, or N) differences in their pulp, but the non-watery pineapple varieties had higher dry matter and soluble sugar content. The metabolomic analysis found 641 metabolites and revealed differential expression of alkaloids, phenolic acids, nucleotide derivatives, lipids, and other metabolites among the seven species. Transcriptome analysis and further KEGG enrichment showed downregulation of 'flavonoid biosynthesis' pathways, differential expression of metabolic pathways, secondary metabolites biosynthesis, plant-pathogen interaction, and plant hormone signal transduction. We believe this study will provide critical molecular data supporting a deeper understanding of pineapple translucency formation and greatly benefit future research on this commercially important crop.

Comparisons of care practices for very preterm infants and their short-term outcomes in two tertiary centers in northwest and south China: A retrospective cohort study.

BACKGROUND: Care practices for very preterm infants and the mortality and morbidity of the infants vary widely among countries and regions with different levels of economic development, including the different areas in China. We aimed to compare the obstetric and delivery room practices of two representative tertiary newborn centers in the northwestern and southern regions of China and the mortality and morbidity of their very preterm infants. METHODS: A retrospective cohort study was conducted. Very preterm infants born between 220/7 and 316/7 weeks of gestation, and admitted to Qinghai Red Cross Hospital (QHH) and Shenzhen Baoan Women's and Children's Hospital (SZH) from January 1, 2018 to December 31, 2020, were included. The infants' characteristics and short-term outcomes, and the hospitals' care practices were compared between the two cohorts. RESULTS: Three hundred and two infants in QHH and 505 infants in SZH were enrolled, and the QHH cohort was more mature than the SZH cohort was (gestational age 30.14 (29.14-31.14) vs. 29.86 (27.86-31.00 weeks, respectively), p < 0.001). Fewer antenatal steroids and more tracheal intubations were used in QHH than in SZH [(73.8% vs. 90.9%, p < 0.001) and (68.2% vs. 35.0%, p < 0.001, respectively)]. The odds of mortality [aOR = 10.31, 95%CI: (6.04, 17.61)], mortality or major morbidity [aOR = 5.95, 95%CI: (4.05, 8.74)], mortality despite active treatment [aOR = 3.14, 95%CI: (1.31, 7.53)], mortality or major morbidity despite active treatment [aOR = 3.35, 95%CI: (2.17, 5.17)], moderate or severe bronchopulmonary dysplasia [aOR = 3.66, 95%CI: (2.20, 6.06)], and severe retinopathy of prematurity [aOR = 3.24, 95%CI: (1.19, 8.83)] were higher in the QHH cohort. No significant difference in the rate of severe neurological injury or necrotizing enterocolitis ≥ Stage 2 was found between the cohorts. CONCLUSION: Obstetric and delivery room care practices used in the management of very preterm infants differed considerably between the QHH and SZH cohorts. Very preterm infants born in QHH have higher odds of mortality or severe morbidity compared with those born in SZH.

Genome-Wide Identification and Expression Patterns of AcSWEET Family in Pineapple and AcSWEET11 Mediated Sugar Accumulation.

Pineapple (Ananas comosus L.) is an important fruit crop in tropical regions, and it requires efficient sugar allocation during fruit development. Sugars Will Eventually be Exported Transporters (SWEETs) are a group of novel sugar transporters which play critical roles in seed and fruit development. However, the function of AcSWEETs remains unknown in the sugar accumulation. Herein, 17 AcSWEETs were isolated and unevenly located in 11 chromosomes. Analysis of a phylogenetic tree indicated that 17 genes were classified into four clades, and the majority of AcSWEETs in each clade shared similar conserved motifs and gene structures. Tissue-specific gene expression showed that expression profiles of AcSWEETs displayed differences in different tissues and five AcSWEETs were strongly expressed during fruit development. AcSWEET11 was highly expressed in the stage of mature fruits in 'Tainong16' and 'Comte de paris', which indicates that AcSWEET11 was important to fruit development. Subcellular localization analysis showed that AcSWEET11 was located in the cell membrane. Notably, overexpression of AcSWEET11 could improve sugar accumulation in pineapple callus and transgenic tomato, which suggests that AcSWEET11 might positively contribute to sugar accumulation in pineapple fruit development. These results may provide insights to enhance sugar accumulation in fruit, thus improving pineapple quality in the future.

[Determination Methods of 2019 Novel Coronavirus (SARS-CoV-2)].

This study summarized the determination methods and principles of 2019 novel coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2). The advantages and limitations of several methods was compared, which can provide a basis for the selection of 2019 novel coronavirus clinical diagnosis methods.

Genome-wide association study of the loci and candidate genes associated with agronomic traits in Amomum villosum Lour.

Amomum villosum Lour. (A. villosum) is a valuable herbaceous plant that produces the famous traditional Chinese medicine Amori Fructus. Identifying molecular markers associated with the growth of A. villosum can facilitate molecular marker-assisted breeding of the plant. This study employed 75 A. villosum accessions as the test material and utilized 71 pairs of polymorphic simple sequence repeat (SSR) molecular markers to genotype the population. The study analyzed the association between SSR markers and phenotypic traits through the linkage imbalance and population structure analysis. Candidate genes associated with the molecular markers were also identified. The results showed that the phenotypic diversity index range of the 12 agronomic traits was 4.081-4.312 and conformed to a normal distribution. Moreover, 293 allelic variations were detected in the 75 accessions, with an average of 5.32 amplified alleles per loci, ranging from 3 to 8. The maximum number of amplified alleles for AVL12 was 8. The population structure and cluster analysis indicated that the accessions could be divided into two subgroups. Using the mixed linear model (MLM) model of population structure (Q)+kinship matrix (K) for association analysis, three SSR molecular markers significantly associated with the agronomic traits were detected. Fluorescence quantification was used to analyze the expression levels of six candidate genes, and it was found that three of the genes were differentially expressed in phenotypically different accessions. This study is the first to use SSR markers for genome-wide association study (GWAS) mapping and identification of the associated agronomic traits in A. villosum. The results of this study provide a basis for identifying genetic markers for growth traits for marker-assisted breeding in A. villosum.

Amelioration of gait and balance disorders by rosuvastatin is associated with changes in cerebrovascular reactivity in older patients with hypertensive treatment.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration.

Cascade Nanoreactor Employs Mitochondrial-Directed Chemodynamic and δ-ALA-Mediated Photodynamic Synergy for Deep-Seated Oral Cancer Therapy.

The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. A cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment is introduced. Utilizing iron oxide and mesoporous silica, the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA), is developed. Triphenylphosphine (TPP) modification facilitates mitochondrial targeting, while tumor cell membrane (TCM) coating provides homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM demonstrate efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggers δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria undergoes Fenton chemistry for CDT. The synergistic interaction of PDT and CDT increases cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic mechanisms, ultimately leading to tumor cell death. PDT/CDT-induced apoptosis generates δ-ALA-containing apoptotic bodies, enhancing antitumor efficacy in deep tumor cells. The anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment.

Integrated Analysis of Metabolomics, Flavoromics, and Transcriptomics for Evaluating New Varieties of Amomum villosum Lour.

Amomum villosum Lour. (A. villosum) is the original plant of the medicinal and culinary spice Amomi Fructus (Sharen) and is an important economic crop in the Lingnan region of China. During the cultivation and production of A. villosum, prolonged reliance on single asexual reproduction has exacerbated the degradation of its varieties, leading to inconsistent yields and quality. Building upon earlier cultivar selection efforts, this study provides a comprehensive evaluation of two newly bred A. villosum varieties (A11 and A12) from perspectives including plant traits, product characteristics, active ingredients, and multi-omics analysis. It was found that A12 plants display enhanced robustness, more aromatic fruits, higher yields, and elevated levels of bornyl acetate, A11 shows the advantage of a high camphor content, and the different metabolites and differentially expressed genes of the two varieties were significantly enriched in multiple metabolic pathways. Additionally, A12 contained more terpenoids and substances with aromatic odors such as sweet, fruity, floral, and green. Furthermore, a key gene (Wv_032842) regulating the acetylation of bornyl was discovered, and its significantly higher expression, in A12. In conclusion, this study has a guiding significance for the evaluation of germplasm resources and the breeding of excellent varieties of A. villosum.

Excessive Dietary Salt Intake Exacerbates Cognitive Impairment Progression and Increases Dementia Risk in Older Adults.

OBJECTIVES: To investigate excessive dietary salt intake as an independent risk factor of cognitive impairment and dementia in older adults. DESIGN: Prospective, population-based cohort study. SETTINGS AND PARTICIPANTS: Two thousand forty-one community residents aged ≥60 years were recruited between April 2007 and August 2009 from the Shandong area of China. MEASUREMENTS: Participants were classified into low, mild, moderate, and high salt intake groups according to urinary sodium measurements for 7 consecutive days. Global cognitive function was assessed at baseline and biennially thereafter using the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Dementia Rating Scale (DRS), and Informant Questionnaire on Cognitive Decline in the Elderly. Demographics and apolipoprotein E (APOE) genotype were also obtained for each participant. Participants were monitored for 11.4 ± 2.0 years. RESULTS: During follow-up, MMSE, MoCA, and DRS scores decreased progressively faster with increasing salt intake (Padjustment < 0.05 among all intake groups). In total, 319 participants (13.74 per 1000 person-years) developed cognitive impairment. Compared with the low salt intake group, cognitive impairment risk was increased by 75% in the mild group (Padjustment = 0.027), 180% in the moderate group (Padjustment < 0.001), and 330% in the high group (Padjustment < 0.001) after adjustment for age, education, mean, and variability in visit-to-visit systolic and diastolic blood pressure, and APOE genotype. The hazard ratio for cognitive impairment increased by 1.59 (95% CI 1.40-1.79) with each 1-SD increment in salt intake after confounder adjustment (Padjustment < 0.001). CONCLUSIONS AND IMPLICATIONS: Excessive dietary salt impairs cognitive function and increases cognitive impairment risk in older adults independently of known risk factors, including hypertension and APOE genotype.

Excessive dietary sodium intake augments long-term risk of atrial fibrillation in older adults with hyperglycemia: A community-based prospective cohort study.

AIM: Studies investigating the association between sodium intake and new-onset atrial fibrillation (AF) have come to controversial results. This study aimed to assess the effect of excessive sodium intake on new-onset AF in individuals with hyperglycemia. METHODS: Between April 2007 and November 2011, 2841 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Dietary sodium intake was estimated using 24-hour urine collection within seven consecutive days. Fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were assessed. New-onset AF was diagnosed using ICD-10 with codes I48 (I48.0 - I48.9) during follow-up. RESULTS: The findings were that excessive sodium intake significantly and independently increased the risk of new-onset AF in older adults with hyperglycemia: hazard ratio (HR) 1.525 [95% confidence interval 1.147;2.029] adjusted P = 0.004. The risk of new-onset AF increased by 29.3% (HR 1.293 [1.108;1.509] adjusted P = 0.001) with a one-standard deviation increase in sodium intake. Excessive sodium intake synergistically interacted with hyperglycemia on the increased risk of new-onset AF (HR 1.599 [1.342;1.905] adjusted P < 0.001 for FPG and HR 1.516 [1.271;1.808] adjusted P < 0.001 for HbA1c). CONCLUSION: Our findings indicate that excessive sodium intake independently enhances the risk of new-onset AF among patients with hyperglycemia. A sodium-restricted diet may perhaps result in a multiplier effect on reducing the risk of new-onset AF.

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma.

Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first-line therapy was well tolerable and had potentially favorite efficacy in PD-L1-positive patients with R/M OSCC.

Short-term prognosis of very-preterm infants of ethnic minorities and Han nationality at high altitude: a single-center, retrospective study.

OBJECTIVE: We aimed to analyze the perinatal care of very-preterm infants (VPIs) in plateau areas of China and to explore any differences in short-term outcomes between ethnic minorities and Han nationality. METHODS: VPIs with gestational age (GA) <32 weeks admitted to Qinghai Red Cross Hospital from 1 January 2018 to 31 December 2020 were enrolled. Maternal information, neonatal information, perinatal care and discharge outcomes were retrospectively collected and analyzed. RESULTS: A total of 302 VPIs were examined, including 143 (47.4%) ethnic minority infants and 159 (52.6%) Han infants. Mothers of ethnic minority infants were significantly younger than those of Han infants (27 y vs. 30 y, p < .001). There were no differences in the incidence of assisted reproduction, multiple pregnancies, maternal hypertension, clinical chorioamnionitis or premature rupture of membranes >18 h between ethnic minority mothers and Han mothers. Lower proportions of cesarean section and incidence of maternal diabetes were observed in ethnic minority mothers than in Han mothers [(9.1 vs.17.6%, p < .05) and (42.7 vs. 57.9%, p < .05, respectively)]. Meanwhile, fewer antenatal steroids were used in minority group than Han group (65.7 vs. 81.1%, p < .05). No significant differences in rates of death, active treatment, necrotizing enterocolitis stage ≥2, moderate-to-severe BPD, and incidence of severe retinopathy of prematurity in VPIs were found between the two groups and in all GA subgroups. Severe neurological injury was significantly less common in the minority newborns than in the Han infants (1.2 vs. 6.1%, p < .05). Compared with Han group, no excess risk of death, death or major morbidity, death despite active treatment, death or major morbidity despite active treatment was observed in ethnic minorities, with or without adjusting for gestational age and prenatal steroids. CONCLUSIONS: Short-term prognosis of VPIs of ethnic minorities were similar to those of Han nationality.

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery.

Objectives: The role of re-irradiation after salvage surgery for recurrent oral cavity cancer (OCC) is controversial. We evaluated the efficacy and safety of adjuvant toripalimab (PD-1 antibody) in this patient setting. Materials and methods: In this phase II study, patients after salvage surgery with OCC occurring in an area of previously irradiated were enrolled. Patients received toripalimab 240 mg once every 3 weeks for 12 months, or combined with S-1 orally for 4-6 cycles. The primary endpoint was 1-year progression-free survival (PFS). Results: Between April 2019 and May 2021, 20 patients were enrolled. Sixty percent patients had ENE or positive margins, 80% were restaged as stage IV, and 80% were previously treated with chemotherapy. The 1-year PFS and overall survival (OS) were 58.2%, and 93.8%, respectively, for patients with CPS ≥ 1, which was significantly better than those of the real-world reference cohort (p = 0.001 and 0.019). No grade 4-5 toxicities were reported, and only one patient experienced grade 3 immune related adrenal insufficiency and discontinued treatment. The 1-year PFS and OS were significantly different for patients with CPS < 1, CPS 1-19 and CPS ≥ 20 (p = 0.011 and 0.017, respectively). The peripheral blood B cell proportion was also correlated with PD in 6 months (p = 0.044). Conclusion: Adjuvant toripalimab or combine with S-1 after salvage surgery showed improved PFS compared with a real-world reference cohort in recurrent, previously irradiated OCC, and favorable PFS were observed in patients with a higher CPS and peripheral B cell proportion. Further randomized trials are warranted.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

Expression patterns, activities and carbohydrate-metabolizing regulation of sucrose phosphate synthase, sucrose synthase and neutral invertase in pineapple fruit during development and ripening.

Differences in carbohydrate contents and metabolizing-enzyme activities were monitored in apical, medial, basal and core sections of pineapple (Ananas comosus cv. Comte de paris) during fruit development and ripening. Fructose and glucose of various sections in nearly equal amounts were the predominant sugars in the fruitlets, and had obvious differences until the fruit matured. The large rise of sucrose/hexose was accompanied by dramatic changes in sucrose phosphate synthase (SPS) and sucrose synthase (SuSy) activities. By contrast, neutral invertase (NI) activity may provide a mechanism to increase fruit sink strength by increasing hexose concentrations. Furthermore, two cDNAs of Ac-sps (accession no. GQ996582) and Ac-ni (accession no. GQ996581) were first isolated from pineapple fruits utilizing conserved amino-acid sequences. Homology alignment reveals that the amino acid sequences contain some conserved function domains. Transcription expression analysis of Ac-sps, Ac-susy and Ac-ni also indicated distinct patterns related to sugar accumulation and composition of pineapple fruits. It suggests that differential expressions of multiple gene families are necessary for sugar metabolism in various parts and developmental stages of pineapple fruit. A cycle of sucrose breakdown in the cytosol of sink tissues could be mediated through both Ac-SuSy and Ac-NI, and Ac-NI could be involved in regulating crucial steps by generating sugar signals to the cells in a temporally and spatially restricted fashion.

Birth growth curves of neonates in high-altitude areas: A cross-sectional study.

Background: Since the current commonly used birth growth curves are unsuitable for neonates in high-altitude areas; this study aimed to establish birth growth curves for full-term neonates residing at 2,000-3,000 m. Methods: This cross-sectional study retrospectively analyzed the physical measurement data of 1,546 full-term neonates delivered at the Red Cross Hospital of Qinghai province, China, from July 2021 to April 2022. The percentile curves of birth weight, length, and head circumference of neonates of different gestational ages and genders were developed using curve fitting. The newly developed birth-weight percentile reference was compared with the INTERGROWTH-21st Neonatal Growth Curve (International Standard) and the Chinese Neonate Growth Curve (Chinese Standard). Results: The median birth weight, length, and head circumference of the study population were 3,200 g, 52.0 cm, and 32.8 cm, respectively, except for the group with a gestational age of 37 weeks. The growth indicators of male infants in all groups were higher than those of the female infants (P < 0.05). We found differences between the newly developed birth-weight percentile curves in the high-altitude areas and the International and Chinese Standards. Conclusion: Establishing birth growth curves corresponding to altitude may be more suitable than the existing standards for local medical staff to conduct health assessments of neonates.

Metabolomic and transcriptomic analyses reveal the mechanism of sweet-acidic taste formation during pineapple fruit development.

Pineapple (Ananas comosus L.) is one of the most valuable subtropical fruit crop in the world. The sweet-acidic taste of the pineapple fruits is a major contributor to the characteristic of fruit quality, but its formation mechanism remains elusive. Here, targeted metabolomic and transcriptomic analyses were performed during the fruit developmental stages in two pineapple cultivars ("Comte de Paris" and "MD-2") to gain a global view of the metabolism and transport pathways involved in sugar and organic acid accumulation. Assessment of the levels of different sugar and acid components during fruit development revealed that the predominant sugar and organic acid in mature fruits of both cultivars was sucrose and citric acid, respectively. Weighted gene coexpression network analysis of metabolic phenotypes and gene expression profiling enabled the identification of 21 genes associated with sucrose accumulation and 19 genes associated with citric acid accumulation. The coordinated interaction of the 21 genes correlated with sucrose irreversible hydrolysis, resynthesis, and transport could be responsible for sucrose accumulation in pineapple fruit. In addition, citric acid accumulation might be controlled by the coordinated interaction of the pyruvate-to-acetyl-CoA-to-citrate pathway, gamma-aminobutyric acid pathway, and tonoplast proton pumps in pineapple. These results provide deep insights into the metabolic regulation of sweetness and acidity in pineapple.