Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.

Background: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine. Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 µg·kg-1 (RD0.5 Group) or 1.0 µg·kg-1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 µg·kg-1·h-1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery. Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness. Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 µg·kg-1) may be a more appropriate choice. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study.

OBJECTIVE: Heterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients. METHODS: We conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed. RESULTS: The study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel's diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel's diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient's age, the lesion site and size, and coexisting diseases. CONCLUSIONS: Only one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel's diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

The Role Played by Mitochondria in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) refers to an endocrine disorder syndrome that are correlated with multiple organs and systems. PCOS has an effect on women at all stages of their lives, and it has an incidence nearly ranging from 6% to 20% worldwide. Mitochondrial dysfunctions (e.g., oxidative stress, dynamic imbalance, and abnormal quality control system) have been identified in patients and animal models of PCOS, and the above processes may play a certain role in the development of PCOS and its associated complications. However, their specific pathogenic roles should be investigated in depth. In this review, recent studies on the mechanisms of action of mitochondrial dysfunction in PCOS and its associated clinical manifestations are summarized from the perspective of tissues and organs, and some studies on the treatment of the disease by improving mitochondrial function are reviewed to highlight key role of mitochondrial dysfunction in this syndrome.

[Characterization of sequences, expression profiling, and natural allelic variation analysis of the MYC gene family in sorghum (Sorghum bicolor)].

Sorghum aphid (Melanaphis sacchari) and head smut fungi (Sporisorium reilianum) infesting sorghum cause delayed growth and development, and reduce yield and quality. This study use bioinformatics and molecular biological approaches to profile the gene expression pattern during sorghum development and under pest infestation, and analyzed the natural allelic DNA variation of sorghum MYC gene family. The findings provide insights for potential application in breeding the stress resistant and high productivity sorghum varieties. The results indicated that there are 28 MYC genes identified in sorghum genome, distributed on 10 chromosomes. The bHLH_MYC_N and HLH domains are the conserved domains of the MYC gene in sorghum. Gene expression analysis showed that SbbHLH35.7g exhibited high expression levels in leaves, SbAbaIn showed strong expression in early grains, and SbMYC2.1g showed high expression levels in mature pollen. In anti-aphid strains at the 5-leaf stage, SbAbaIn, SbLHW.4g and SbLHW.2g were significantly induced in leaves, while SbbHLH35.7g displayed the highest expression level in panicle tissue, which was significantly induced by the infection of head smut. Promoter cis-element analysis identified methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA) and MYB-binding sites related to drought-stress inducibility. Furthermore, genomic resequencing data analysis revealed natural allelic DNA variations such as single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) for the key SbMYCs. Protein interaction network analysis using STRING indicated that SbAbaIn interacts with TIFYdomain protein, and SbbHLH35.7g interacts with MDR and imporin. SbMYCs exhibited temporal and spatial expression patterns and played vital roles during the sorghum development. Infestation by sugarcane aphids and head smut fungi induced the expression of SbAbaIn and SbbHLH35.7g, respectively. SbAbaIn modulated the jasmonic acid (JA) pathway to regulate the expression of defensive genes, conferring resistance to insects. On the other hand, SbbHLH35.7g participated in detoxification reactions to defend against pathogens.

mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients.

Recent progress of CDK4/6 inhibitors' current practice in breast cancer.

Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

Decreased FGF23 inhibits placental angiogenesis via the ERK1/2-EGR-1 signaling pathway in preeclampsia.

PURPOSE: This study aimed to investigate the expression of fibroblast growth factor 23 (FGF23) in pregnant women with preeclampsia and elucidate its role in promoting placental angiogenesis through the ERK1/2-EGR-1 signaling pathway. METHODS: Serum FGF23 levels were measured by ELISA in healthy pregnant women and patients with preeclampsia during the first, second, and third trimesters of pregnancy. Wound healing, Transwell, and tube formation assays were performed to investigate the effects of FGF23 on cell migration, invasion and tube formation. The expression of vascular endothelial growth factor A (VEGF-A) and its upstream signaling molecules, p-ERK, and EGR-1, in placental tissues was detected by RT-qPCR and western blotting. Additionally, the effect of FGF23 on VEGF-A, p-ERK, and EGR-1 expression was further explored in vitro. RESULTS: Serum FGF23 levels increased with gestational age. During the third trimester, the control group exhibited a more pronounced increase in FGF23 levels than the preeclampsia group. Administering exogenous FGF23 promoted trophoblast cell migration, invasion and enhanced tube formation in vascular endothelial cells. The expression levels of VEGF-A, p-ERK, and EGR-1 in the placental tissues were significantly lower in the preeclampsia group than in the control group. In vitro experiments confirmed that FGF23 up-regulated VEGF-A expression through the p-ERK/EGR-1 signaling pathway. CONCLUSION: The serum level of FGF23 decreased in pregnant women with preeclampsia, inhibiting the ERK1/2-EGR-1 pathway and resulting in decreased expression of VEGF-A, thereby inhibiting placental angiogenesis. This could be a potential mechanism involved in the progression of preeclampsia.

Comprehensive evaluation of smoking exposures and their interactions on DNA methylation.

BACKGROUND: Smoking impacts DNA methylation, but data are lacking on smoking-related differential methylation by sex or dietary intake, recent smoking cessation (<1 year), persistence of differential methylation from in utero smoking exposure, and effects of environmental tobacco smoke (ETS). METHODS: We meta-analysed data from up to 15,014 adults across 5 cohorts with DNA methylation measured in blood using Illumina's EPIC array for current smoking (2560 exposed), quit < 1 year (500 exposed), in utero (286 exposed), and ETS exposure (676 exposed). We also evaluated the interaction of current smoking with sex or diet (fibre, folate, and vitamin C). FINDINGS: Using false discovery rate (FDR < 0.05), 65,857 CpGs were differentially methylated in relation to current smoking, 4025 with recent quitting, 594 with in utero exposure, and 6 with ETS. Most current smoking CpGs attenuated within a year of quitting. CpGs related to in utero exposure in adults were enriched for those previously observed in newborns. Differential methylation by current smoking at 4-71 CpGs may be modified by sex or dietary intake. Nearly half (35-50%) of differentially methylated CpGs on the 450 K array were associated with blood gene expression. Current smoking and in utero smoking CpGs implicated 3049 and 1067 druggable targets, including chemotherapy drugs. INTERPRETATION: Many smoking-related methylation sites were identified with Illumina's EPIC array. Most signals revert to levels observed in never smokers within a year of cessation. Many in utero smoking CpGs persist into adulthood. Smoking-related druggable targets may provide insights into cancer treatment response and shared mechanisms across smoking-related diseases. FUNDING: Intramural Research Program of the National Institutes of Health, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, Chief Scientist Office of the Scottish Government Health Directorates and the Scottish Funding Council, Medical Research Council UK and the Wellcome Trust.

Clinical features and imaging examination assessment of cervical lymph nodes for thyroid carcinoma.

BACKGROUNDS: The purpose of this study is to investigate the relationship between clinical characteristics and cervical lymph node metastasis (LNM) in patients with thyroid carcinoma, as well as estimate the preoperative diagnosis values of ultrasound (US) and contrast enhanced computed tomography (CECT) examinations on the neck for detection of cervical LNM in thyroid carcinoma. METHODS: A retrospective analysis of 3 026 patients with surgically proven thyroid carcinoma was conducted. Patients' clinical characteristics, including gender, age, tumor size, bilateral lesions, multifocality, adenomatous nodules, Hashimoto's thyroiditis (HT), and extrathyroidal extension, were collected to explore their association with cervical LNM in thyroid carcinoma. Preoperative assessments for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were conducted through US and CECT. The diagnostic value of US, CECT and US combined with CECT for detection of LNM located in various cervical compartments was estimated based on the pathological results. RESULTS: The risk of cervical LNM was higher in thyroid cancer patients who were male, age < 55 years old, tumor size > 10 mm, bilateral lesions, and extrathyroidal extension, while multifocality, adenomatous nodules and HT had no significant effect on LNM. US, CECT and US combined with CECT all had a higher sensitivity to LLNM (93.1%, 57.8%, 95.4%) than to CLNM (32.3%, 29.0%, 43.4%). US and CECT had a high specificity to both CLNM and LLNM (94.3-97.8%). CONCLUSION: Preoperative clinical characteristics and imaging examinations on patients with thyroid carcinoma are crucial to the evaluation of cervical lymph nodes and conducive to individualizing surgical treatments by clinicians. US combined with CECT are superior to single US or CECT alone in detection of CLNM and LLNM.

O-GlcNAc has crosstalk with ADP-ribosylation via PARG.

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation "eraser", ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs.

Factors influencing extrathyroidal extension of papillary thyroid cancer and evaluation of ultrasonography for its diagnosis: a retrospective analysis.

Pathologists usually explore extrathyroidal extensions (ETEs) in thyroid cancer; however, sonographers are often not concerned with ETEs. We investigated factors influencing ETEs and the efficacy of ultrasound evaluation of thyroid capsule invasion. We retrospectively analysed 1933 papillary thyroid carcinoma patients who underwent thyroidectomy during 2018-2021. Patients were divided into three groups: no ETE, minor ETE (mETE), and gross ETE. Clinical characteristic differences were assessed using binary logistic regression analysis to identify ETE predictors, and the kappa test was performed to analyse consistency between ultrasonographic and pathological diagnoses of ETE. The mETE group was more likely to have larger tumour diameters and more extensive lymph node metastasis (LNM) than the no ETE group and more likely to be diagnosed in the isthmus. In the multivariate logistic regression analysis, longest tumour diameter, lesion site, LNM extent, and thyroglobulin concentration were significant mETE predictors. Minimal consistency existed between pathological and ultrasonographic examinations for neighbouring tissue invasion. Many clinical differences were observed between the no ETE and mETE groups, suggesting the importance of considering mETE. Therefore, sonographers should pay more attention to relationships between nodules and capsule and indicate these on ultrasound reports to provide more accurate preoperative ETE information for surgeons.

Processable circularly polarized luminescence material enables flexible stereoscopic 3D imaging.

Endowing three-dimensional (3D) displays with flexibility drives innovation in the next-generation wearable and smart electronic technology. Printing circularly polarized luminescence (CPL) materials on stretchable panels gives the chance to build desired flexible stereoscopic displays: CPL provides unusual optical rotation characteristics to achieve the considerable contrast ratio and wide viewing angle. However, the lack of printable, intense circularly polarized optical materials suitable for flexible processing hinders the implementation of flexible 3D devices. Here, we report a controllable and macroscopic production of printable CPL-active photonic paints using a designed confining helical co-assembly strategy, achieving a maximum luminescence dissymmetry factor (glum) value of 1.6. We print customized graphics and meter-long luminous coatings with these paints on a range of substates such as polypropylene, cotton fabric, and polyester fabric. We then demonstrate a flexible textile 3D display panel with two printed sets of pixel arrays based on the orthogonal CPL emission, which lays an efficient framework for future intelligent displays and clothing.

Design and synthesis of 1H-benzo[d]imidazole selective HDAC6 inhibitors with potential therapy for multiple myeloma.

Pan-HDAC inhibitors exhibit significant inhibitory activity against multiple myeloma, however, their clinical applications have been hampered by substantial toxic side effects. In contrast, selective HDAC6 inhibitors have demonstrated effectiveness in treating multiple myeloma. Compounds belonging to the class of 1H-benzo[d]imidazole hydroxamic acids have been identified as novel HDAC6 inhibitors, with the benzimidazole group serving as a specific linker for these inhibitors. Notably, compound 30 has exhibited outstanding HDAC6 inhibitory activity (IC50 = 4.63 nM) and superior antiproliferative effects against human multiple myeloma cells, specifically RPMI-8226. Moreover, it has been shown to induce cell cycle arrest in the G2 phase and promote apoptosis through the mitochondrial pathway. In a myeloma RPMI-8226 xenograft model, compound 30 has demonstrated significant in vivo antitumor efficacy (T/C = 34.8%) when administered as a standalone drug, with no observable cytotoxicity. These findings underscore the immense potential of compound 30 as a promising therapeutic agent for the treatment of multiple myeloma.

Understanding the role of environmental and socioeconomic factors in the geographic variation of breast cancer risk in the US-wide Sister Study.

OBJECTIVE: To describe the geographic pattern of breast cancer incidence in a nationwide prospective cohort and investigate whether environmental exposures and/or neighborhood socioeconomic status explain observed geographic disparities. METHODS: Using accelerated failure time models with a spatial random effect term, we mapped the health region-level association between residential location and breast cancer incidence for 44,707 participants in the Sister Study after controlling for established individual-level breast cancer risk factors. We performed a variable selection process to select environmental exposures [i.e., ambient nitrogen dioxide (NO2) and fine particulate matter (PM2.5), PM2.5 chemical composition, outdoor light at night (LAN), ambient noise, ultraviolet radiation, and greenspace] and neighborhood-level factors [i.e., population density and area deprivation index (ADI)] that predicted breast cancer incidence and quantified the spatial variation explained by the selected factors. We also considered whether the geographic pattern and predictors were similar when restricting to estrogen receptor-positive (ER+) tumors. RESULTS: We observed a spatial patterning in the incidence of overall breast cancer (Moran's I = 16.7, p < 0.05) and ER+ breast cancer (Moran's I = 13.2, p < 0.05), with a lower risk observed in the South and Southeast and a greater risk in the Northwest and certain areas of the Midwest and Northeast. NO2, LAN, and ADI explained 21.4% of the spatial variation in overall breast cancer incidence whereas NO2, PM2.5 chemical composition, LAN, greenspace, and ADI together explained 63.3% of the spatial variation in ER+ breast cancer incidence. CONCLUSIONS: Our findings provide additional evidence for a role of environmental exposures in breast cancer incidence and suggest that geographic-based risk factors may vary according to breast cancer subtype. Our findings support the need for additional research to quantify the relative contributions of geographic-based risk factors for breast cancer.

Next-generation sequencing-based detection in a breast MMPMN patient with EGFR T790M mutation: a rare case report and literature review.

Multiple primary malignant neoplasms (MPMNs) are difficult to identify from the metastasis or recurrence of malignant tumors. Additionally, the genetic mutations in each primary tumor vary from each other; therefore, it is critical to explore potential abnormal genes. Next-generation sequencing (NGS) technology has emerged as a reliable approach for detecting mutated genes in primary tumors and can provide several targeted therapeutic options for patients with MPMNs. Here, we report a case of metachronous multiple primary malignant neoplasm (MMPMN) patient with primary ovarian and breast cancer. Targeted NGS genetic profiling revealed a rare EGFR T790M mutation in this patient's primary breast tumor tissue, which has only been reported previously in breast cancer (BC). Based on the NGS results, osimertinib was recommended for this patient. Although this patient did not receive osimertinib because of gastrointestinal hemorrhage, this case highlights the significance of NGS technology in the diagnosis and treatment of MPMNs.

Influence of Cmr1 in the Regulation of Antioxidant Function Melanin Biosynthesis in Aureobasidium pullulans.

We have successfully identified the transcription factor Cmr1 from the fungus Aureobasidium pullulans Hit-lcy3T, which regulates melanin biosynthesis genes. Bioinformatics analysis revealed that the Cmr1 gene encodes a protein of 945 amino acids, containing two Cys2His2 zinc finger domains and a Zn(II)2Cys6 binuclear cluster domain located at the N-terminus of Cmr1. To investigate the function of the Cmr1 gene, we performed gene knockout and overexpression experiments. Our results showed that Cmr1 is a key regulator of melanin synthesis in Hit-lcy3T, and its absence caused developmental defects. Conversely, overexpression of Cmr1 significantly increased the number of chlamydospores in Hit-lcy3T and improved melanin production. RT-qPCR analysis further revealed that overexpression of Cmr1 enhanced the expression of several genes involved in melanin biosynthesis, including Cmr1, PKS, SCD1, and THR1. Melanin extracted from the Hit-lcy3T was characterized using UV and IR spectroscopy. Furthermore, we assessed the antioxidant properties of Hit-lcy3T melanin and found that it possesses strong scavenging activity against DPPH·, ABTS·, and OH·, but weaker activity against O2-·. These findings suggest that Hit-lcy3T melanin holds promise for future development as a functional food additive.

A step closer to real practice: Integrated tandem photocatalysis-biofilm process towards degradation of crude oil.

Intimately coupled photocatalysis and biodegradation (ICPB) systems represent a promising wastewater treatment technology. The implementation of ICPB systems for oil spill treatment is a pressing concern. In this study, we developed an ICPB system comprising BiOBr/modified g-C3N4 (M-CN) and biofilms for the treatment of oil spills. The results demonstrate that the ICPB system achieved the rapid degradation of crude oil, outperforming the single photocatalysis and biodegradation methods by degrading 89.08 ± 5.36% within 48 h. The combination of BiOBr and M-CN formed a Z-scheme heterojunction structure, enhancing the redox capacity. The interaction between the holes (h+) and the negative charge on the biofilm surface promoted the separation of electrons (e-) and h+, thereby accelerating the degradation process of crude oil. Moreover, ICPB system maintained an excellent degradation ratio after three cycles and its biofilms progressively adapted to the adverse effects of crude oil and light. The microbial community structure remained stable throughout the degradation of crude oil, with Acinetobacter and Sphingobium identified as the dominant genera in biofilms. The proliferation of the Acinetobacter genus appeared to be the main factor contributing to the promotion of crude oil degradation. Our work demonstrates that the integrated tandem strategies perhaps represent a feasible pathway toward practical crude oil degradation.

Development and validation of a gene expression-based nomogram to predict the prognosis of patients with cholangiocarcinoma.

AIM: To establish and validate a prognostic nomogram of cholangiocarcinoma (CCA) using independent clinicopathological and genetic mutation factors. METHODS: 213 patients with CCA (training cohort n = 151, validation cohort n = 62) diagnosed from 2012 to 2018 were included from multi-centers. Deep sequencing targeting 450 cancer genes was performed. Independent prognostic factors were selected by univariate and multivariate Cox analyses. The clinicopathological factors combined with (A)/without (B) the gene risk were used to establish nomograms for predicting overall survival (OS). The discriminative ability and calibration of the nomograms were assessed using C-index values, integrated discrimination improvement (IDI), decision curve analysis (DCA), and calibration plots. RESULTS: The clinical baseline information and gene mutations in the training and validation cohorts were similar. SMAD4, BRCA2, KRAS, NF1, and TERT were found to be related with CCA prognosis. Patients were divided into low-, median-, and high-risk groups according to the gene mutation, the OS of which was 42.7 ± 2.7 ms (95% CI 37.5-48.0), 27.5 ± 2.1 ms (95% CI 23.3-31.7), and 19.8 ± 4.0 ms (95% CI 11.8-27.8) (p < 0.001), respectively. The systemic chemotherapy improved the OS in high and median risk groups, but not in the low-risk group. The C-indexes of the nomogram A and B were 0.779 (95% CI 0.693-0.865) and 0.725 (95% CI 0.619-0.831), p < 0.01, respectively. The IDI was 0.079. The DCA showed a good performance and the prognostic accuracy was validated in the external cohort. CONCLUSION: Gene risk has the potential to guide treatment decision for patients at different risks. The nomogram combined with gene risk showed a better accuracy in predicting OS of CCA than not.

A Novel Clinical Prognostic Model for Breast Cancer Patients with Malignant Pleural Effusion: Avoiding Chemotherapy in Low-Risk Groups?

Purpose: Malignant pleural effusion (MPE) is a severe complication in patients with advanced cancer that is associated with a poor prognosis. Breast cancer is the second leading cause of MPE after lung cancer. We therefore aim to describe clinical characteristics of the patients with MPE combined with breast cancer and construct a machine learning-based model for predicting the prognosis of such patients. Methods: This study is a retrospective and observational study. Least absolute shrinkage and selection operator (LASSO) and univariate Cox regression analyses were applied to identify eight key clinical variables, and a nomogram model was established. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses. Results: 196 patients with both MPE and breast cancer (143 in the training group and 53 in the ex-ternal validation group) were analyzed in this study. The median overall survival in two cohorts was 16.20 months and 11.37 months. Based on the ROC curves for 3-, 6-, and 12-month survival, the areas under the curves were 0.824, 0.824, and 0.818 in the training set and 0.777, 0.790, and 0.715 in the validation set, respectively. In the follow-up analysis, both systemic and intrapleural chemotherapy significantly increased survival in the high-risk group compared to the low-risk group. Conclusion: Collectively, MPE confers a poor prognosis in breast cancer patients. We have developed a first-ever survival prediction model for breast cancer patients with newly diagnosed MPE and validated the model using an independent cohort.