Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Study on the Correlation between Urinary Sodium and Potassium Excretion and Blood Pressure in Adult Hypertensive Inpatients of Different Sexes.

Objective: This study aims to understand the difference in the influence of urinary sodium and potassium excretion on blood pressure in patients of different sexes with hypertension by analyzing the relationship between urinary sodium and potassium excretion and blood pressure. Methods: In this cross-sectional study, 606 hospitalized patients with essential hypertension were recruited from 16 hospitals in the Shanxi Province between June 2018 and December 2019. These patients were grouped by sex, with 368 males and 238 females. Basic information and relevant serum biochemical indexes of patients in the two groups were recorded. The 24-hour urinary sodium and potassium excretion were measured, and 24-hour ambulatory blood pressure monitoring was performed simultaneously. This was done to analyze and compare the relationship between urinary sodium and urinary potassium excretion and blood pressure in adult hospitalized patients of different sexes with hypertension. Results: The 24-hour urinary sodium excretion in male patients with hypertension was significantly higher than that in female patients (P < 0.001). There was no significant difference in 24-hour urinary potassium excretion between male patients with hypertension and female patients. Spearman correlation analysis showed that 24-hour urinary sodium excretion was positively correlated with 24-hour SBP and nSBP in male patients (P < 0.05), while 24-hour urinary potassium excretion was negatively correlated with 24-hour SBP and nSBP in male patients (P < 0.05). The 24-hour urinary sodium in female patients was significantly positively correlated with 24-hour SBP, 24-hour DBP, SBP, dDBP, nSBP, and nDBP (P < 0.01). The 24-hour urinary potassium was significantly negatively correlated with nSBP (P < 0.05). Multiple stepwise linear regression showed that 24-hour urinary sodium excretion was still significantly positively correlated with 24-hour SBP and nSBP in male patients with hypertension after adjusting for various confounding factors. Conclusion: High urinary sodium and low urinary potassium excretion are closely related to elevated blood pressure in adult patients with hypertension, and there are sex differences.

[Chemical functiomics: a new direction for modern research on traditional Chinese medicine--a case study of core component group of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs].

To analyze the complex relationship between chemical components and functions of traditional Chinese medicine, this study put forward the concept of "chemical functiomics" for the first time and defined the connotation and significance of "chemical functiomics" based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, which provided a new direction for modern research on traditional Chinese medicine. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Encyclopedia of Traditional Chinese Medicine(ETCM), and Natural Product Activity and Species Source Database(NPASS) were searched for the chemical components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs included in the Science of Chinese Materia Medica with the names of the above drugs as the key words. The pharmacological actions corresponding to the functions of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs were standardized with MESH2021 terms(Chinese version) as the standard. Discovery Studio 4.5 was used to calculate absorption, distribution, metabolism, excretion, and toxicity(ADMET) molecular descriptors. Principal component analysis and 95% confidence ellipse calculation were carried out using Origin 2021. Hydrogenation of chemical components and Murcko skeleton calculation were completed using the CDK algorithm and the RDKit algorithm packages in the KNIME 4.3.2. The results showed that there were 404 common components of hemostatic drugs and blood-activating/stasis-resolving drugs, accounting for 17.3% of the total components. The plotted chemical function diagrams of hemostatic drugs and blood-activating/stasis-resolving drugs showed that the pharmacological action group acting as a bridge connected the function group and the chemical composition group, and different combinations of pharmacological effects indicated different functions. The unique Murcko skeleton of the core components of hemostatic drugs mainly included naphthoquinone and tetracyclic triterpenes, while those of blood-activating/stasis-resolving drugs were mainly alkaloids. Based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, this study provides references for the study of "chemical functiomics" and support for the research on the functional material basis of traditional Chinese medicine.

A rare Bochdalek hernia in an adult: a case report.

BACKGROUND: Symptomatic Bochdalek hernias are found mainly in infants in respiratory distress and occur rarely in adults. CASE PRESENTATION: We report a rare case of Bochdalek hernia associated with developmental abnormalities in an adult who exhibited acute chest pain and dyspnea on exertion. CONCLUSIONS: This case highlights the importance of the differential diagnosis of acute left-sided chest pain and antenatal examination.

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety.

Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion of Connexin 26 (CX26) in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover, CX26-conditional knockout (CX26-cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion of CX26, decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore, CX26-cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.

Identifying EGFR mutations in lung adenocarcinoma by noninvasive imaging using radiomics features and random forest modeling.

OBJECTIVES: The tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models. METHODS: Five hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (n = 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: The performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point. CONCLUSION: Our results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool. KEY POINTS: • Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status. • In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions. • The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.

Amelioration of Inflammatory Cytokines Mix Stimulation: A Pretreatment of CD137 Signaling Study on VSMC.

Previous studies showed little CD137 expressed in normal vascular smooth muscle cells (VSMCs) and it is important to find a valid way to elevate it before studying its function. The level of CD137 was detected by RT-PCR, western blot, and flow cytometry, respectively. CD137 signaling activation was activated by agonist antibody and measured through phenotype transformation indicators and cell functions. Proteins in supernatants were detected by ELISA. The total CD137 elevates under different concentrations of CM treatment. Among these, 25 ng/ml CM treatment increases the CD137 expression mostly. However, flow cytometry demonstrates that 10 ng/ml CM elevates surface CD137 more significantly than other concentrations and reaches the peak at 36 h. At 10 ng/ml, but not 25 ng/ml CM pretreatment, the levels of phenotype related proteins such as SM-MHC, α-SMA, and calponin decrease while vimentin and NFATc1 increase, suggesting that VSMCs undergo phenotype transformation. Transwell, CCK-8 assay, and ELISA showed that the ability of VSMCs viability, migration, and IL-2 and IL-6 secretion induced by CD137 signaling was significantly enhanced by the pretreatment of 10 ng/ml CM. This research suggested that 10 ng/ml CM pretreatment is more reasonable than other concentrations when exploring CD137 function in VSMCs.

Interaction effects on cytochrome P450 both in vitro and in vivo studies by two major bioactive xanthones from Halenia elliptica D. Don.

The major components, 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1) and 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) isolated from Halenia elliptica D. Don (Gentianaceae), could cause vasodilatation in rat coronary artery with different mechanisms. In this work, high-performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMS-IT-TOF) was used to clarify the metabolic pathways, and CYP450 isoform involvement of HM-1 and HM-5 were also studied in rat. At the same time, in vivo inhibition effects of HM-1 and ethyl acetate extracts from origin herb were studied. Three metabolites of HM-5 were found in rat liver microsomes (RLMs); demethylation and hydroxylation were the major phase I metabolic reactions for HM-5. Multiple CYP450s were involved in metabolism of HM-1 and HM-5. The inhibition study showed that HM-5 inhibited Cyp1a2, 2c6 and 2d2 in RLMs. HM-1 inhibited activities of Cyp1a2, Cyp2c6 and Cyp3a2. In vivo experiment demonstrated that both HM-1 and ethyl acetate extracts could inhibit Cyp3a2 in rats. In conclusion, the metabolism of xanthones from the origin herb involved multiple CYP450 isoforms; in vitro, metabolism of HM-5 was similar to that of its parent drug HM-1, but their inhibition effects upon CYP450s were different; in vivo, Cyp3a2 could be inhibited by HM-1 and ethyl acetate extracts.

In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats.

Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.ex D. Don. The present study was designed to investigate the metabolic profiles of FR429 in rats in vivo. Using liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF), total eight metabolites were found in rat bile and urine after intravenous administration of FR429, but could not be detected in plasma. These metabolites were ellagic acid, mono-methylated FR429, ellagic acid methyl ether glucuronide, ellagic acid methyl ether diglucuronide, ellagic acid dimethyl ether glucuronide, and ellagic acid dimethyl ether diglucuronide. It was concluded that methylation and subsequent glucuronidation were the major metabolic pathways of FR429 in rats in vivo. This is the first report on the in vivo metabolism of the purified ellagitannin in rats.

[Treatment of Guishen Zhiyang Recipe for Senile Pruritus Patients with Blood Deficiency and Hy- peractivity of Gan-yang Syndrome].

Objective To observe the clinical efficacy of Guishen Zhiyang Recipe (GZR) in trea- ting senile pruritus patients with blood deficiency and hyperactivity of Gan-yang syndrome (BDHGYS) and to study the mechanism in nervous-endocrine-immune systems. Methods Ninety senile pruritus pa- tients were assigned to the treatment group and the control group by complete randomized lot, 45 in each group. Totally 41 patients in the treatment group and 38 patients in the control group completed the trial. Patients in the treatment group took GZR, while those in the control group took Fuyang Granule (FG). Ex- ternal application of Binghuang Fule Soft Ointment was performed to all patients. The therapeutic course for all was 8 weeks. Symptoms and efficacy changes in skin lesion were observed in the two groups. Lev- els of stem cell factor (SCF) , dynorphin (DYN) , testosterone (T) , estradiol (E2) , and IL-4 were detec- ted in the two groups using double antibody sandwich ELISA. Results Compared with before treatment, pruritus degree, scratching area, scaling, lichenoid lesion, irritability and restlessness, dysphoria, dry pharynx, dizziness, and tinnitus all decreased in the two groups after 8 weeks of treatment (P <0. 05). Scores of Chinese medical syndromes all decreased after 4 and 8 weeks of treatment (P <0. 05). Levels of SCF and DYN obviously decreased in the two groups after 4 and 8 weeks of treatment (P <0. 05,P < 0. 01). Compared with the control group, obvious improvement was seen in pruritus degree, scratching number, scaling, irritability and restlessness , dysphoria, dizziness , and tinnitus(P <0. 05) ; total scores of Chinese medical syndromes decreased (P <0. 05) ; SCF also decreased (P <0. 05) in the treatment group after 8 weeks of treatment. Conclusions Based on external application of Binghuang Fule Soft Ointment, GZR showed better efficacy than that of the control. It had certain roles in regulating related mediator levels that might affect nervous-endocrine-immune systems.

Effect of Berberine on promoting the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters.

BACKGROUND: Berberine (BBR), as a new medicine for hyperlipidemia, can reduce the blood lipids in patients. Mechanistic studies have shown that BBR activates the extracellular-signal regulated kinase pathway by stabilizing low-density-lipoprotein receptor mRNA. However, aside from inhibiting the intestinal absorption of cholesterol, the effects of BBR on other metabolic pathways of cholesterol have not been reported. This study aimed to investigate the action of BBR on the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters. METHODS: Golden hamsters were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia, followed by oral treatment with 50 and 100 mg/kg/day of BBR or 10 and 30 mg/kg/day of lovastatin for 10 days, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), transaminases, and total bile acid in the serum, liver, bile and feces were measured using an enzyme-linked immunosorbent assay. The cholesterol (as well as coprostanol) levels in the liver, bile and feces were determined by gas chromatography-mass spectrometry. RESULTS: The HFD hamsters showed significantly hyperlipidemic characteristics compared with the normal hamsters. Treatment with BBR for 10 days reduced the serum TC, TG and LDL-C levels in HFD hamsters by 44-70, 34-51 and 47-71%, respectively, and this effect was both dose- and time-dependent. Initially, a large amount of cholesterol accumulated in the hyperlipidemic hamster livers. After BBR treatment, reductions in the liver cholesterol were observed by day 3 and became significant by day 7 at both doses (P < 0.001). Meanwhile, bile cholesterol was elevated by day 3 and significantly increased at day 10 (P < 0.001). BBR promoted cholesterol excretion from the liver into the bile in hyperlipidemic hamsters but not in normal hamsters, and these results provide a link between the cholesterol-lowering effect of BBR with cholesterol excretion into the bile. CONCLUSIONS: We conclude that BBR significantly promoted the excretion of cholesterol from the liver to the bile in hyperlipidemic hamsters, which led to large decreases in the serum TC, TG and LDL-C levels. Additionally, compared with lovastatin, the BBR treatment produced no obvious side effects on the liver function.

Nail Fusion Plasty: Nail Cosmetic Results and Assessment Criteria of Nail Reconstruction.

PURPOSE: This study aimed to develop a scoring system for evaluating the nail appearance after nail fusion plasty of the duplicated thumb, and to investigate the operation indication of the combination procedure and its effect on the postoperative nail appearance. METHODS: The nail fusion plasty technique was carried out in 20 patients with congenital thumb duplication. The patients were followed up to observe the appearance of nail, and the results were assessed by our nail appearance evaluation criteria. RESULTS: Twenty patients were followed up for 18 to 92 months (48 months on average). According to our criteria, we achieved excellent results in 12 cases, good in 6 cases, fair in 1 case, and poor in 1 case. CONCLUSIONS: The combination procedure is recommended when the size of the thumb is less than 80% of the size of the normal side or the width of the nail is less than 80% of that of the normal side. Satisfactory results can be obtained by careful operation. The newly devised scoring system assesses the nail appearance in a very comprehensive manner.

Three new asperentin derivatives from the algicolous fungus Aspergillus sp. F00785.

Three new asperentin-type compounds, 6-O-α-d-ribosylasperentin (1) and 6-O-α-d-ribosyl-8-O-methylasperentin (2) and 5-hydroxyl-6-O-methylasperentin (3), along with asperentin (4) and its known analogues (5-9), were isolated from a halotolerant Aspergillus sp. strain F00785, an endotrophic fungus from marine alga. Their structures were determined using extensive NMR and HRESIMS spectroscopic analysis, including the X-ray crystallographic data for the assignment of the absolute configurations of compound 9. Compound 4 exhibited highly potent inhibitory activity against crop pathogens, Colletotrichum gleosporioides Penz. and Colletotrichum gleosporioides (Penz.) Sacc.

Biotransformation and in vitro metabolic profile of bioactive extracts from a traditional Miao-nationality herbal medicine, Polygonum capitatum.

Polygonum capitatum Buch.-Ham.ex D. Don, a traditional Miao-nationality herbal medicine, has been widely used in the treatment of various urologic disorders. Recent pharmacological studies demonstrated that a pure compound, FR429, isolated from the ethanol extracts of P. capitatum could selectively inhibit the growth of four hepatocellular carcinoma (HCC) cell lines in a dose-dependent manner. Thus, P. capitatum probably exhibits potential antitumor activity. However, there is very little information on the metabolism of substances present in P. capitatum extracts. In this study, gallic acid, quercetrin, ethanol extracts and ethyl acetate fraction of ethnolic extract (EtOAc fraction) of P. capitatum were cultured anaerobically with rat intestinal bacteria. A highly sensitive and selective liquid chromatography electrospray ionization-ion trap-time of fight mass spectrometry (LC/MSn-IT-TOF) technique was employed to identify and characterize the resulting metabolites. A total of 22 metabolites (M1-M22), including tannins, phenolic acids and flavonoids, were detected and characterized. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of P. capitatum, and the main metabolic pathways were hydrolysis, reduction and oxidation reactions. Our results provided a basis for the estimation of the metabolic transformation of P. capitatum in vivo.

Salivary microbiome is associated with the response to chemoradiotherapy in initially inoperable patients with esophageal squamous cell carcinoma.

Background: The salivary microbiome may interact with chemoradiotherapy through dynamic changes in microbial composition and systemic immunity. We aimed to explore the association between the salivary microbiome and response to chemoradiotherapy in initially inoperable patients with local advanced esophageal squamous cell carcinoma (LAESCC). Methods: Salivary and peripheral blood samples were collected before and after chemoradiotherapy. The microbiome and metabolic pathways were analyzed by 16S ribosomal RNA sequencing and liquid chromatography tandem mass spectrometry/Mass spectrometry analyses. Results: The salivary microbiome exhibited characteristic variations between patients and healthy controls. A significant correlation was found between Prevotella_salivae, Saccharibacteria_TM7_G3_bacterium_HMT_351, and Veillonellaceae_G1_bacterium_HMT_129 and pathological complete response (pCR) in initially inoperable patients who underwent surgery. The PICRUSt suggested that immune diseases and cell motility were different in tumor compared to normal groups. KEGG enrichment analysis showed enriched lipid metabolism, signal transduction, and membrane transport in the tumor group. CD3+CD8 T cells, IL6, IL10, and IFNγ exhibited an increasing trend during the treatment process of chemoradiotherapy. Conclusions: Our study demonstrated that variations in specific saliva taxa associated with host immunomodulatory cells and cytokines could be promising for early efficacy prediction of chemoradiotherapy in initially inoperable patients with LAESCC.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Identification of ALDOB as a novel prognostic biomarker in kidney clear cell renal cell carcinoma.

Kidney clear cell renal cell carcinoma (KIRC) is also the most lethal subtype among all kidney cancer subtypes, posing a severe threat to public health. Therefore, it is crucial to identify new, reliable biomarkers in KIRC. Therefore, it is crucial to identify novel, reliable biomarkers associated with KIRC. We analyzed RNA sequence results from TCGA and several GEO datasets. The commonly deregulated gene, ALDOB, was found in multiple data and confirmed its important prognostic value. Subsequently, we explored the specific mechanism by which ALDOB regulates anti-tumor immunity through in vivo and in vitro experiments. We found that ALDOB may play a role in regulating tumor growth by regulating CD8+ T cell infiltration. This is consistent with the results of our immune infiltration-related analysis. In addition, we have also discovered the effect of ALDOB in previous studies on other cancer types. Finally, we concluded that ALDOB may have potential reference value for immunotherapy and can also be used as an independent predictor of prognosis in KIRC.

The value of intervention with radiotherapy after first-line chemo-immunotherapy in locally advanced or metastatic esophageal squamous cell carcinoma: A multi-center retrospective study.

Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0-8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1-34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0-15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.