Arthroscopic Resection for Extra-articular Ganglion Cysts of Gastrocnemius Near Vessels.

Extra-articular ganglion cysts arising from the gastrocnemius tendon near popliteal vessels can cause pain and claudication. Open resection of this kind of cyst has been described frequently because the vessels can be well protected with a retractor. However, it's a challenge to remove cysts that are near vessels under arthroscopy, because a retractor cannot be used in arthroscopic surgery. This article will report a method of arthroscopic resection for extra-articular ganglion cysts near popliteal vessels.

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay.

Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

Zero-valent iron enhanced methane production of anaerobic digestion by reinforcing microbial electron bifurcation coupled with direct inter-species electron transfer.

Zero-valent iron (ZVI) can facilitate methanogens of anaerobic digestion (AD). However, the impact of ZVI on the micro-energetic strategies of AD microorganisms remains uncertain. This study aimed to elucidate the development of an energy conservation model involving direct interspecies electron transfer (DIET) and electron bifurcate (EB) by using four types of ZVI. Overall, the ZVI addition resulted in a substantial increase in methane production (1.26 to 2.18 times higher), and the effect of boron (B) doped ZVI was particularly pronounced. The underlying mechanism may be the formation of energy harvest pathway related to DIET. In detail, B-doped ZVI could enhance its interfacial binding to cytochrome c. Decreased polar solvation energy from 20.473 to 1.509 kJ/mol is beneficial for electron transfer, thereby augmenting the flavin-bounded Cytc activity and DIET process. Besides, ZVI-enhanced EB enzyme activity like HdrA2B2C2-MvhAGD could improve the EB process, which can couple with DIET for electron transfer and energy conservation. Energy analysis based on EB-coupled DIET metabolism pathways demonstrated that the ATP saved in this coupled model theoretically line in 0.25 to 0.5 mol ATP/mol substrate. Overall, this study offers valuable insights into microbial energetic strategies pertaining to the utilization of conductive materials, with the target of enhancing methane recovery efficiency from organic waste.

Phase angle - A screening tool for malnutrition, sarcopenia, and complications in gastric cancer.

BACKGROUND: Patients with gastric cancer (GC) are more likely to experience malnutrition and muscle wasting. This study aims to investigate the potential of phase angle (PhA) as a screening tool for identifying malnutrition and sarcopenia in GC patients, as well as its association with short-term outcomes after radical gastrectomy. METHODS: This cross-sectional study enrolled patients diagnosed with GC at The Affiliated People's Hospital of Jiangsu University from October 2021 to September 2022. PhA was measured using bioelectrical impedance analysis. Computed tomography scan images were analyzed for body composition at the level of the third lumbar vertebra. Malnutrition was diagnosed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Sarcopenia diagnosis was based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. RESULTS: A total of 248 patients with GC were analyzed, including 188 patients who underwent radical gastrectomy. Of these, 71.4 % (n = 177) were male and 28.6 % (n = 71) were female and the median overall age was 68 years (IQR: 61-72 years). According to GLIM criteria, 49.2 % (n = 122) of patients were malnourished and 19.8 % (n = 49) had sarcopenia based on AWGS criteria. A one-degree decrease in PhA was significantly associated with GLIM malnutrition (Odds Ratio [OR] = 8.108, 95 % CI:3.181-20.665) and sarcopenia (OR = 2.903, 95 % CI:1.170-7.206). PhA exhibited fair to good diagnostic accuracy in identifying GLIM malnutrition (male: AUC = 0.797; female: AUC = 0.816) and sarcopenia (male: AUC = 0.814; female: AUC = 0.710). Low PhA (OR = 3.632, 95 % CI: 1.686-7.824) and operation time (OR = 2.434, 95 % CI:1.120-5.293) were independently associated with the risk of postoperative complications. CONCLUSIONS: PhA can serve as a reliable screening tool for identifying patients at risk of malnutrition, sarcopenia, and postoperative complications in GC.

The Role of Thoracic Vertebral Body Dosimetry in Minimizing Acute Hematologic Toxicities of Patients With Non-Small Cell Lung Cancer Receiving Lung Radiation Therapy and Immunotherapy.

PURPOSE: Hematologic toxicities (HTs) are among the most common toxicities of combined immunotherapy and radiation therapy (RT). It remains essential to prevent RT-induced HTs because they can cause treatment discontinuation (influencing antitumoral effects) and because lymphopenia might dampen the effects of immunotherapy. To date, there are no studies examining the effect of thoracic vertebral body (TVB) RT dose on HTs in patients with non-small cell lung cancer receiving combined lung RT and programmed cell death (ligand) 1 immunotherapy. METHODS AND MATERIALS: For standardization, all doses were reported as 2-Gy equivalents (EQD2). Mirroring publications before the immunotherapy era, TVB volumes referred to T1-T10, and specific dosimetric parameters (DmeanEQD2, V5EQD2-V60EQD2) were analyzed. Logistic regression estimated associations between grade ≥3 HTs (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability (NTCP) models were constructed by logistic regression analysis modeling for HT3+. Receiver operating characteristic (ROC) analysis delineated TVB dosimetric thresholds, the stratification of which was able to evaluate post-RT absolute lymphocyte count and immunotherapy responses. Areas under the curve (AUCs) for NTCP models were corroborated by bootstrapping (optimism-corrected) methodology. RESULTS: In 132 patients, there were 26 (19.7%) instances of HT3+. On multivariate analysis, DmeanEQD2 and V5EQD2 to V20EQD2 were associated with HT3+ (P < .05 for all). The NTCP models illustrated a 50% probability of HT3+ at a DmeanEQD2 = 39.8 Gy, V5EQD2 = 87.4%, V10EQD2 = 77.0%, and V20EQD2 = 68.4%. ROC analysis delineated optimal thresholds of HT3+ with DmeanEQD2 ± 30.2 Gy, V5EQD2 ± 69.1%, V10EQD2 ± 64.6%, and V20EQD2 ± 53.5%. Patients treated with values above those cutoffs had over double the risk of HT3+, with significant differences in post-RT absolute lymphocyte count and immunotherapy responses (P < .05 for all). AUCs for each individual parameter ranged from 0.743 to 0.798, and combining all 4 aforementioned cutoffs into a ROC curve resulted in a qualitatively higher AUC (0.836). CONCLUSIONS: This hypothesis-generating work suggests that TVB dosimetry may equate with HT3+ in patients with non-small cell lung cancer undergoing combined lung RT/immunotherapy. Applying TVB dose constraints in this population could reduce HT3+ and avoid dampening of immunotherapy responses, but prospective validation is required.

Enhanced thermophilic dark fermentation of hydrogen production from food waste by Fe-modified biochar.

The industrialization of hydrogen production through dark fermentation of food waste faces challenges, such as low yields and unpredictable fermentation processes. Biochar has emerged as a promising green additive to enhance hydrogen production in dark fermentation. Our study demonstrated that the introduction of Fe-modified biochar (Fe-L600) significantly boosted hydrogen production during thermophilic dark fermentation of food waste. The addition of Fe-L600 led to a remarkable 31.19% increase in hydrogen yield and shortened the time needed for achieving stabilization of hydrogen production from 18 h to 12 h. The metabolite analysis revealed an enhancement in the butyric acid pathway as the molar ratio of acetic acid to butyric acid decreased from 3.09 to 2.69 but hydrogen yield increased from 57.12 ± 1.48 to 76.78 ± 2.77 mL/g, indicating Fe-L600 improved hydrogen yield by regulating crucial metabolic pathways of hydrogen production. The addition of Fe-L600 also promoted the release of Fe2+ and Fe3+ and increased the concentrations of Fe2+ and Fe3+ in the fermentation system, which might promote the activity of hydrogenase and ferredoxin. Microbial community analysis indicated a substantial increase in the relative abundance of Thermoanaerobacterium after thermophilic dark fermentation. The relative abundances of microorganisms responsible for hydrolysis and acidogenesis were also observed to be improved in the system with Fe-L600 addition. This research provides a feasible strategy for improving hydrogen production of food waste and deepens the understanding of the mechanisms of biochar.

High HPK1+PD-1+TIM-3+CD8+ T cells infiltration predicts poor prognosis to immunotherapy in NSCLC patients.

At present the efficacy of immune checkpoint inhibitors (ICIs) remains limited. The lack of responsiveness in certain patients may be attributed to CD8+ T cell exhaustion within the tumor microenvironment (TME). Hematopoietic progenitor kinase 1 (HPK1) has been identified as a mediator of T cell dysfunction, leading to our hypothesis that HPK1 positive exhausted CD8+ T cells could serve as a predictor for ICIs' efficacy in NSCLC patients, and potentially indicate key cellular subset causing ICIs resistance. Here, we retrospectively collected tumor tissue samples from 36 NSCLC patients who underwent first-line immunotherapy. Using multiplex immunohistochemistry, we visualized various PD-1+CD8+ T cell subsets and explore biomarkers for response. The analysis endpoints included overall response rate (ORR), progression free survival (PFS), and overall survival (OS), correlating them with levels of cell infiltration or effective density. We found that the proportion of PD-1+CD8+ T cell subsets did not align with predictions for ORR, PFS, and OS. Conversely, a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells was identified as an independent risk factor for both PFS (P = 0.019) and OS (P = 0.03). These cells were found to express the highest levels of Granzyme B, and the secretion of Granzyme B in CD8+ T cell subsets was related to TCF-1. In conclusion, these data suggest that a high infiltration of HPK1+PD-1+TIM-3+CD8+ T cells correlates with poor clinical outcomes in NSCLC patients receiving immunotherapy. These cells may represent terminally exhausted T cells that fail to respond to ICIs, thereby laying the groundwork for the potential integration of HPK1 inhibitors with immunotherapy to enhance treatment strategy.

Comprehensive analysis of thirteen-gene panel with prognosis value in Multiple Myeloma.

BACKGROUND: Although there are many treatments for Multiple myeloma (MM), patients with MM still unable to escape the recurrence and aggravation of the disease. OBJECTIVE: We constructed a risk model based on genes closely associated with MM prognosis to predict its prognostic value. METHODS: Gene function enrichment and signal pathway enrichment analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, univariate and multivariate Cox regression analysis, Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) analysis were used to identify the prognostic gene signature for MM. Finally, the prognostic gene signature was validated using the Gene Expression Omnibus (GEO) database. RESULTS: Thirteen prognostic genes were screened by univariate Cox analysis and LASSO regression analysis. Multivariate Cox analysis revealed risk score to be an independent prognostic factor for patients with MM [Hazard Ratio (HR) = 2.564, 95% Confidence Interval (CI) = 2.223-2.958, P< 0.001]. The risk score had a high level of predictive value according to ROC analysis, with an area under the curve (AUC) of 0.744. CONCLUSIONS: The potential prognostic signature of thirteen genes were assessed and a risk model was constructed that significantly correlated with prognosis in MM patients.

Prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit.

OBJECTIVE: To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. METHODS: Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system. RESULTS: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). CONCLUSION: The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

Exploring low-dose radiotherapy to overcome radio-immunotherapy resistance.

Immune checkpoint inhibitors (ICIs) have revolutionized the current treatment landscape for cancer, yet the response rates of ICIs remain unmet. Synergistic with immunotherapy, low-dose radiotherapy (LDRT) has been demonstrated to activate anti-tumor immunity - a transition from traditional radiation therapy geared toward local radical treatment to a type of immunological adjuvant. As such, studies utilizing LDRT to enhance the efficacy of immunotherapy have been increasing preclinically and clinically. This paper reviews the recent strategies of using LDRT to overcome the resistance of ICIs, as well as providing potential opportunities in cancer treatment. Despite the potential of LDRT in immunotherapy is recognized, the mechanisms behind this form of treatment remain largely elusive. Thus, we reviewed history, mechanisms and challenges associated with this form of treatment, as well as different modes of its application, to provide relatively accurate practice standards for LDRT as a sensitizing treatment when combined with immunotherapy or radio-immunotherapy.

First Report of Fusarium Root Rot of Tobacco Caused by Fusarium fujikuroi in Guangdong Province, China.

From March to June 2022, Fusarium tobacco root rot broke out in Shaoguan Guangdong Province, China, affecting approximately 15% of tobacco production fields, with an incidence of 24% to 66%. In the early stage, the lower leaves showed chlorosis, and the roots became black. In the later stage, the leaves became browned and withered, the root cortices were broken and shed, and only a small number of roots were left. Eventually, the entire plant died. Six diseased plant samples (cv. yueyan 97) from Shaoguan (113.8°E, 24.8°N) were collected as test materials. The diseased root tissues (4×4 mm) were surface-sterilized using 75% ethanol for 30 s and 2% NaOCl for 10 min, rinsed 3 times with sterile water and incubated for 4 days on potato dextrose agar (PDA) medium at 25 °C. Fungal colonies were subcultured on fresh PDA, grown for the next 5 d and purified by single-spore separation. Eleven isolates with similar morphological characteristics were obtained. Their colonies were white and fluffy, and the bottoms of the culture plates were pale pink after 5 days of incubation. The macroconidia were slender, slightly curved and measured 18.54~45.85 µm×2.35~3.84 µm (n=50), with 3 to 5 septa. The microconidia were oval or spindle shaped, with one to two cells, and measured 5.56~16.76 µm×2.32~3.86 µm (n=50). Chlamydospores were absent. Such characteristics are typical of the genus Fusarium (Booth C, 1971). The SGF36 isolate was chosen for further molecular analysis. The TEF-1α and ß-tubulin genes (Pedrozo et al.2015) were amplified. Based on a phylogenetic tree (neighbor-joining method and 1,000 bootstrap values) obtained using multiplex alignments of concatenations of these two genes from 18 Fusarium species, SGF36 was grouped into a clade with Fusarium fujikuroi strain 12-1 (MK443268.1/MK443267.1) and F. fujikuroi isolate BJ-1 (MH263736.1/MH263737.1). To further identity the isolate, five additional gene sequences (rDNA-ITS (OP862807.1), RPB2, histone 3, calmodulin, and mitochondrial small subunit) (Pedrozo et al.2015), were subjected to BLAST searches in GenBank, and the results indicated that they were most similar to F. fujikuroi sequences, with sequence identities greater than 99%. The phylogenetic tree obtained using six genes except mitochondrial small subunit gene showed that SGF36 was grouped together with four F. fujikuroi strains to form a single clade. Pathogenicity was determined by the inoculation of wheat grains with fungi in potted tobacco plants. The SGF36 isolate was inoculated onto sterilized wheat grains, which were then incubated at 25 °C for 7 d. Thirty wheat grains with fungi were added to 200 g of sterilized soil, which was then mixed well and placed into pots. One six-leaf-stage tobacco seedling (cv. yueyan 97) was planted in each pot. A total of 20 tobacco seedlings were treated. Another 20 control seedlings were treated with wheat grains without fungi. All seedlings were placed in a greenhouse at 25 °C with 90% relative humidity. After 5 d, the leaves of all inoculated seedlings showed chlorosis, and the roots became discolored. No symptoms were observed in the controls. The fungus was reisolated from symptomatic roots and confirmed to be F. fujikuroi based on the TEF-1α gene sequence. No F. fujikuroi isolates were recovered from control plants. F. fujikuroi was previously reported to be associated with rice bakanae disease (Ram et al., 2018), soybean root rot (Zhao et al., 2020) and cotton seedling wilt (Zhu et al., 2020). To our knowledge, this is the first report of F. fujikuroi causing root wilt on tobacco in China. The identification of the pathogen may help to establish appropriate measures for controlling this disease.

LINC00659 cooperated with ALKBH5 to accelerate gastric cancer progression by stabilising JAK1 mRNA in an m6 A-YTHDF2-dependent manner.

BACKGROUND: N6-methyladenosine (m6 A) RNA modification is known as a common epigenetic regulation form in eukaryotic cells. Emerging studies show that m6 A in noncoding RNAs makes a difference, and the aberrant expression of m6 A-associated enzymes may cause diseases. The demethylase alkB homologue 5 (ALKBH5) plays diverse roles in different cancers, but its role during gastric cancer (GC) progression is not well known. METHODS: The quantitative real-time polymerase chain reaction, immunohistochemistry staining and western blotting assays were used to detect ALKBH5 expression in GC tissues and human GC cell lines. The function assays in vitro and xenograft mouse model in vivo were used to investigate the effects of ALKBH5 during GC progression. RNA sequencing, MeRIP sequencing, RNA stability and luciferase reporter assays were performed to explore the potential molecular mechanisms involved in the function of ALKBH5. RNA binding protein immunoprecipitation sequencing (RIP-seq), RIP and RNA pull-down assays were performed to examine the influence of LINC00659 on the ALKBH5-JAK1 interaction. RESULTS: ALKBH5 was highly expressed in GC samples and associated with aggressive clinical features and poor prognosis. ALKBH5 promoted the abilities of GC cell proliferation and metastasis in vitro and in vivo. The m6 A modification on JAK1 mRNA was removed by ALKBH5, which resulted in the upregulated expression of JAK1. LINC00659 facilitated ALKBH5 binding to and upregulated JAK1 mRNA depending on an m6 A-YTHDF2 manner. Silencing of ALKBH5 or LINC00659 disrupted GC tumourigenesis via the JAK1 axis. JAK1 upregulation activated the JAK1/STAT3 pathway in GC. CONCLUSION: ALKBH5 promoted GC development via upregulated JAK1 mRNA expression mediated by LINC00659 in an m6 A-YTHDF2-dependent manner, and targeting ALKBH5 may be a promising therapeutic method for GC patients.

Prognostic value of an eighteen-genes panel in acute myeloid leukemia by analyzing TARGET and TCGA databases.

BACKGROUND: Acute myeloid leukemia (AML) has a poor prognosis, and the current 5-year survival rate is less than 30%. OBJECTIVE: The present study was designed to identify the significant genes closely related to AML prognosis and predict the prognostic value by constructing a risk model based on their expression. METHODS: Using bioinformatics (Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, univariate and multivariate Cox regression analysis, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) analysis) to identify a prognostic gene signature for AML. Finally, The Cancer Genome Atlas (TCGA) database was used to validate this prognostic signature. RESULTS: Based on univariate and multivariate Cox regression analysis, eighteen prognostic genes were identified, and the gene signature and risk score model were constructed. Multivariate Cox analysis showed that the risk score was an independent prognostic factor [hazard ratio (HR) = 1.122, 95% confidence interval (CI) = 1.067-1.180, P< 0.001]. ROC analysis showed a high predictive value of the risk model with an area under the curve (AUC) of 0.705. CONCLUSIONS: This study evaluated a potential prognostic signature with eighteen genes and constructed a risk model significantly related to the prognosis of AML patients.

A Familial Case of Multiple Endocrine Neoplasia 2A: From Morphology to Genetic Alterations Penetration in Three Generations of a Family.

This paper illustrates a rare syndrome of multiple endocrine neoplasia type 2A (MEN2A) in a family of three generations. In our case, the father, son and one daughter developed phaeochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) over a period of 35 years. Because of the metachronous onset of the disease and lack of digital medical records in the past, the syndrome was not found until a recent fine needle aspiration of an MTC-metastasized lymph node from the son. All resected tumors from the family members were then reviewed and supplemented with immunohistochemical studies, previously wrong diagnoses were then corrected. Further molecular study of targeted sequencing also revealed a RET germline mutation (C634G) in the family tree including the three members with onset of the disease and one granddaughter who had no disease at the time of testing. Despite the syndrome being well-known, it may still be misdiagnosed because of its rarity and long disease onset. A few lessons can be learned from this unique case. Successful diagnosis requires high suspicion and surveillance and a tri-level methodology including a careful review of family history, pathology and genetic counselling.

The Effect of immunotherapy on oligometastatic non-small cell lung cancer patients by sites of metastasis.

Introduction: The efficacy of immunotherapy for treatment of patients with oligometastatic non-small cell lung cancer (NSCLC) at different metastatic sites remains controversial. We investigated the effect of different metastatic sites on immunotherapy for oligometastatic NSCLC following local treatment (LT). Methods: We retrospectively analyzed patients with oligometastatic NSCLC from the latest 2018 registry on the SEER Stat software (8.3.9. Version) and a Chinese single-center cohort. The effects of immunotherapy on OS (overall survival) and CSS (cancer specific survival) were estimated for patients with different metastatic sites. Results: A total of 483 patients in the SEER-18 database and 344 patients in the single-center cohort were included. Immunotherapy was significantly correlated with improved OS (SEER: Hazard ratio 0.754, 95% CI 0.609-0.932; P=0.044; China: Hazard ratio 0.697, 95% CI 0.542-0.896; P=0.005) and CSS (SEER: Hazard ratio 0.743, 95% CI 0.596-0.928; P=0.009; China: Hazard ratio 0.725, 95% CI 0.556-0.945; P=0.018). Subgroup analysis showed that OS was improved after immunotherapy in the BRM (SEER: Hazard ratio 0.565, 95% CI 0.385-0.829; P=0.004; China: Hazard ratio 0.536, 95% CI 0.312-0.920; P=0.024) and MOM (SEER: Hazard ratio 0.524, 95% CI 0.290-0.947; P=0.032; China: Hazard ratio 0.469, 95% CI 0.235-0.937; P=0.032) subgroups, but not in the BOM (SEER: P=0.334; China: P=0.441), LIM (SEER: P=0.301; China: P=0.357), or OTM (SEER: P=0.868; China: P=0.489) subgroups. Conclusions: This study showed that immunotherapy conferred survival benefits on patients with oligometastatic NSCLC. Our subgroup analysis suggested that patients with oligometastatic NSCLC in the brain or multiple organs may particularly benefit from aggressive front-line therapies.

Novel gene signature reveals prognostic model in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a type of hematological malignancy and has a poor prognosis. In our study, we aimed to construct a prognostic model of ALL by identifying important genes closely related to ALL prognosis. We obtained transcriptome data (RNA-seq) of ALL samples from the GDC TARGET database and identified differentially expressed genes (DEGs) using the "DESeq" package of R software. We used univariate and multivariate cox regression analyses to screen out the prognostic genes of ALL. In our results, the risk score can be used as an independent prognostic factor to predict the prognosis of ALL patients [hazard ratio (HR) = 2.782, 95% CI = 1.903-4.068, p < 0.001]. Risk score in clinical parameters has high diagnostic sensitivity and specificity for predicting overall survival of ALL patients, and the area under curve (AUC) is 0.864 in the receiver operating characteristic (ROC) analysis results. Our study evaluated a potential prognostic signature with six genes and constructed a risk model significantly related to the prognosis of ALL patients. The results of this study can help clinicians to adjust the treatment plan and distinguish patients with good and poor prognosis for targeted treatment.

CXCL2 acts as a prognostic biomarker and associated with immune infiltrates in stomach adenocarcinoma.

BACKGROUND: STAD ranked 5th most common in the incidence of malignant tumors and 3rd most common in the death rate of cancer worldwide. CXC chemokines affect the biological progress of various tumors, resulting in therapeutic failure. The role of CXCL2 in STAD was still a mystery. METHODS: The expression, prognostic value, and clinical function of CXCL2 were analyzed using several online bioinformatics tools and clinical tissues. RESULTS: CXCL2 level was significantly upregulated in STAD tissues. Strong correlation was obtained between CXCL2 level and immune cells as well as immune biomarkers. High CXCL2 expression in STAD was correlated with a favorable prognosis. Further analysis revealed that CXCL2, pTNM stage and age were independent factors affecting the prognosis of STAD patients. A predictive nomogram indicated that the calibration plots for the 1-year, 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the entire cohort. Validation analysis revealed that CXCL2 expression was upregulated in STAD and high CXCL2 level had a better overall survival. CXCL2 was associated with resistance to numerous drugs or small molecules in STAD. CONCLUSIONS: We identified CXCL2 as a novel therapeutic target and associated with immune infiltration in STAD.

Multidisciplinary Progress in Obesity Research.

Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country's medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to secondary neuropathy. How to treat obesity and its secondary diseases has become an urgent problem for patients, doctors and society. This article will summarize the multidisciplinary research on obesity and its complications.

Population pharmacokinetics of posaconazole in Chinese pediatric patients with acute leukaemia: Effect of food on bioavailability and dose optimization.

This study aimed to investigate the effect of food on the pharmacokinetics of posaconazole suspension in pediatric patients with acute leukaemia and to recommend optimal dosing strategies. This single-site, prospective, open-label, observational study was conducted in 42 patients and included 186 plasma concentrations of posaconazole. Sparse data were analyzed using population pharmacokinetic modeling. Monte Carlo simulations were conducted to predict the morning trough concentrations at steady-state with the proposed dose of 2-7 mg/kg three times daily (tid) or four times daily (qid) for bodyweights of 10-36 kg. The target concentrations were 700 ng/mL for prophylaxis and 1000 ng/mL for treatment. Dosage regimens with percentage of target attainment (PTA) ≥70% were recommended. A one-compartment model with allometric scaling adequately described the pharmacokinetic profile. The apparent clearance was 9.05 L/h (95% confidence interval [CI] 7.14-11.09) and the apparent volume of distribution was 283 L (95% CI 168-491) for a typical individual of 17.5 kg. The relative bioavailability with high-fat diet was as high as 1.95-fold compared with regular food. Following the intake of regular meals, 4 mg/kg qid was adequate with a PTA ≥ 71.8% for prophylaxis. A dosage of 6 mg/kg qid under a regular diet reached a PTA ≥ 73.4% for treatment. The recommended dosage of posaconazole for prophylaxis and treatment could be predicted by the pharmacokinetic model based on bodyweight and diet type in pediatric patients.