Altered microbial diversity and composition of multiple mucosal organs in cervical cancer patients.

OBJECTIVES: The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients. METHODS: We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases. RESULTS: Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota (pOral_Sob < 0.001, pOral_Shannon = 0.049, pOral_Simpson = 0.013 pFecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota (pVaginal_Pielou = 0.028, pVaginal_Simpson = 0.006). There were also significant differences in the ß-diversity of the microbiota at each site between cases and controls (pOral = 0.002, pFecal = 0.037, pUrine = 0.001, pVaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma (pUrine = 0.036) and lymph node metastasis (pUrine_Sob = 0.027, pUrine_Pielou = 0.028, pUrine_Simpson = 0.021, pUrine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages (p = 0.002), tumor stages (p = 0.001) and lymph node metastasis (p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors. CONCLUSIONS: Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.

Supercapacitively Liquid-Solid Dual-State Optoelectronics.

Photo-transduction of solid-state optoelectronics occurs in semiconductors or their interfaces. Considering the confined active area and interfacial capacitance of solid-state materials, solid-state optoelectronics faces inherent limitations in photo-transduction, especially for bionic vision, and the performance is lower than that of living systems. For example, a photoreceptor generates pA-level photocurrent when absorbing a single photon. Here, a liquid-solid dual-state phototransistor is demonstrated, in which photo-transduction and modulation take place at the microporous interface between semiconductors and water, mimicking principles of the photoreceptor. When operating in the water, an orderly stacked photo-harvesting covalent organic framework layer generates supercapacitively photogating modulation of the channel conductivity via a dual-state interface, achieving responsivity of 4.6 × 1010 A W-1 and detectivity of 1.62 × 1016 Jones at room temperature, several orders of magnitude higher than other photodetectors. Such bio-inspired dual-state optoelectronics enables high-contrast scotopic neuromorphic imaging with responsivity greater than photoreceptors, holding promise for constructing optoelectronic systems with performance beyond conventional solid-state optoelectronics.

A prediction model based on MRI and ultrasound to predict the risk of PAS in patient with placenta previa.

INTRODUCTION: To investigate the risk factors affecting patients with placenta previa (PP) and to construct an effective prediction model for the severity of PAS in PP. METHODS: A total of 240 pregnant women with PP were enrolled in this study. An MRI+Ultrasound-based model was developed to classify patients into placental implantation and non-placental implantation groups. Multivariate nomograms were created based on imaging features. The model was evaluated using Receiver Operating Characteristic (ROC) curve analysis. The predictive accuracy of the nomogram was assessed through calibration plots and decision curve analysis. RESULTS: The MRI+Ultrasound-based prediction model demonstrated favorable discrimination between the placental implantation and non-placental implantation groups. The calibration curve exhibited agreement between the estimated and actual probability of placental implantation. Additionally, decision curve analysis indicated a high clinical benefit across a wide range of probability thresholds. The Area under the ROC curve (AUC) was 0.911 (95 % CI: 0.76-0.947), with a sensitivity of 88.40 % and specificity of 88.10 %. CONCLUSION: The MRI+Ultrasound-based prediction model could be a valuable tool for preoperative prediction of the percentage of implantation. Our study enables obstetricians to conduct more adequate preoperative evaluations.

Hepatitis B virus infection and the risk of gynecologic cancers: a systematic review and meta-analysis.

OBJECTIVES: The relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis. METHODS: Two independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model. RESULTS: We collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09-1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95-1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79-1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13-1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10-1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07-1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14-1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04-2.49, P = 0.032). The results of Begg's and Egger's tests showed no publication bias. CONCLUSIONS: This meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Balancing the nutrient needs: Optimising growth in Malus sieversii seedlings through tailored nitrogen and phosphorus effects.

The impact of nitrogen (N) and phosphorus (P) on the physiological and biochemical processes crucial for tree seedling growth is substantial. Although the study of plant hydraulic traits in response to N and P is growing, comprehensive research on their combined effects remains limited. Malus sieversii, a key ancestral species of modern apples and a dominant species in Xinjiang's Tianshan wild fruit forest, is witnessing a decline due to climate change, pests and diseases, compounded by challenges in seedling regeneration. Addressing this, a 4-year study was conducted to determine the optimal fertilisation method for it. The experiment explored varying levels of N (N10, N20 and N40) and P (P2, P4 and P8), and their combined effects (N20Px: N20P2, N20P4, N20P8; NxP4: N10P4, N20P4 and N40P4), assessing their impact on gas exchange, hydraulic traits, and the interplay among functional traits in Tianshan Mountains' M. sieversii seedlings. Our study revealed that All N-inclusive fertilisers slightly promoted the net photosynthetic rate. N10 significantly increasing leaf hydraulic conductivity. All P-inclusive fertilisers adversely affected hydraulic conductivity. P8, N20P4 and N20P8 notably increased seedlings' vulnerability to embolism. Seedlings can adaptively adjust multiple functional traits in response to nutrient changes. The research suggests N10 and N20 as the most effective fertilisation treatments for M. sieversii seedlings in this region, while fertilisation involving phosphorus is less suitable. This study contributes valuable insights into the specific nutrient needs of it, vital for conservation and cultivation efforts in the Tianshan region.

Population pharmacokinetics and dose optimization of magnesium sulfate in Chinese preeclampsia population.

OBJECTIVE: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. METHODS: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. RESULTS: A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. CONCLUSIONS: The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.

Transcriptomics Reveals the Mechanism of Purpureocillium lilacinum GZAC18-2JMP in Degrading Keratin Material.

Microbial degradation of keratin is characterized by its inherent safety, remarkable efficiency, and the production of copious degradation products. All these attributes contribute to the effective management of waste materials at high value-added and in a sustainable manner. Microbial degradation of keratin materials remains unclear, however, with variations observed in the degradation genes and pathways among different microorganisms. In this study, we sequenced the transcriptome of Purpureocillium lilacinum GZAC18-2JMP mycelia on control medium and the medium containing 1% feather powder, analyzed the differentially expressed genes, and revealed the degradation mechanism of chicken feathers by P. lilacinum GZAC18-2JMP. The results showed that the chicken feather degradation rate of P. lilacinum GZAC18-2JMP reached 64% after 216 h of incubation in the fermentation medium, reaching a peak value of 148.9 µg·mL-1 at 192 h, and the keratinase enzyme activity reached a peak value of 211 U·mL-1 at 168 h, which revealed that P. lilacinum GZAC18-2JMP had a better keratin degradation effect. A total of 1001 differentially expressed genes (DEGs) were identified from the transcriptome database, including 475 upregulated genes and 577 downregulated genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the DEGs revealed that the metabolic pathways related to keratin degradation were mainly sulfur metabolism, ABC transporters, and amino acid metabolism. Therefore, the results of this study provide an opportunity to gain further insight into keratin degradation and promote the biotransformation of feather wastes.

INSM1 is a useful neuroendocrine marker to differentiate pancreatic serous cystadenoma from pancreatic well-differentiated neuroendocrine tumors in cytology and surgical specimens.

INTRODUCTION: Differentiating pancreatic serous cystadenoma (SCA) from well-differentiated neuroendocrine tumors (WDNETs) based on histomorphology is critical yet challenging, particularly in small biopsy samples. Our study aimed to examine the expression profile of INSM1 in cytologic and surgical resection specimens from pancreatic SCA to evaluate its potential as a discriminative marker against pancreatic WDNET. METHODS: We characterized INSM1 immunohistochemistry in 34 patients with pancreatic SCA, comprising 23 surgical resections and 11 cytology specimens. As a control, we used 28 cytology specimens from pancreatic WDNET. Clinical information was retrieved through a review of electronic medical records. RESULTS: All 11 pancreatic SCA cytology specimens and 15 of 23 pancreatic SCA surgical resections exhibited absent INSM1 immunostaining. Each of the remaining eight surgical resection specimens demonstrated 1 % immunoreactivity. In contrast, 27 out of 28 (96 %) pancreatic WDNET cytology specimens were positive for INSM1 immunostaining, with a median immunoreactivity of 90 % and a range of 30-90 %. Overall, INSM1 immunostains perform similarly to chromogranin and synaptophysin in pancreatic SCA. CONCLUSIONS: The results indicate that INSM1 immunohistochemistry staining may serve as a useful neuroendocrine marker to differentiate pancreatic SCA from pancreatic WDNET in clinical practice. To our knowledge, this represents the first large-scale study to evaluate INSM1 immunostaining in surgical and cytology specimens from pancreatic SCA.

CD36-mediated podocyte lipotoxicity promotes foot process effacement.

Background: Lipid metabolism disorders lead to lipotoxicity. The hyperlipidemia-induced early stage of renal injury mainly manifests as podocyte damage. CD36 mediates fatty acid uptake and the subsequent accumulation of toxic lipid metabolites, resulting in podocyte lipotoxicity. Methods: Male Sprague-Dawley rats were divided into two groups: the normal control group and the high-fat diet group (HFD). Podocytes were cultured and treated with palmitic acid (PA) and sulfo-N-succinimidyl oleate (SSO). Protein expression was measured by immunofluorescence and western blot analysis. Boron-dipyrromethene staining and Oil Red O staining was used to analyze fatty acid accumulation. Results: Podocyte foot process (FP) effacement and marked proteinuria occurred in the HFD group. CD36 protein expression was upregulated in the HFD group and in PA-treated podocytes. PA-treated podocytes showed increased fatty acid accumulation, reactive oxygen species (ROS) production, and actin cytoskeleton rearrangement. However, pretreatment with the CD36 inhibitor SSO decreased lipid accumulation and ROS production and alleviated actin cytoskeleton rearrangement in podocytes. The antioxidant N-acetylcysteine suppressed PA-induced podocyte FP effacement and ROS generation. Conclusions: CD36 participated in fatty acid-induced FP effacement in podocytes via oxidative stress, and CD36 inhibitors may be helpful for early treatment of kidney injury.

An activatable fluorescent-photoacoustic dual-modal probe for highly sensitive imaging of nitroxyl in vivo.

Nitroxyl (HNO) plays a vital role in various biological functions and pharmacological activities, so the development of an excellent near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modality probe is crucial for understanding HNO-related physiological and pathological progression. Herein, we proposed and synthesized a novel NIRF/PA dual probe (QL-HNO) by substituting an indole with quinolinium in hemicyanine for the sensitive detection of exogenous and endogenous HNO in vivo. The designed probe showed the highest sensitivity in NIRF mode and a desirable PA signal-to-noise ratio for HNO detection in vitro and was further applied for NIRF/PA dual-modal imaging of HNO with high contrast in living cells and tumor-bearing animals. Based on the excellent performance of QL-HNO, we believe that this study provides a promising molecular tool for further understanding of HNO-related physiological and pathological progression.

The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis.

As a fatal occupational disease with limited therapeutic options, molecular mechanisms underpinning silicosis are still undefined. Herein, single-cell RNA sequencing of the lung tissue of silicosis mice identified two monocyte subsets, which were characterized by Cxcl10 and Mmp14 and enriched in fibrotic mouse lungs. Both Cxcl10+ and Mmp14+ monocyte subsets exhibited activation of inflammatory marker genes and positive regulation of cytokine production. Another fibrosis-unique neutrophil population characterized by Ccl3 appeared to be related to the pro-fibrotic process, specifically the "inflammatory response". Meanwhile, the proportion of monocytes and neutrophils was significantly higher in the serum of silicosis patients and slices of lung tissue from patients with silicosis further validated the over-expression of Cxcl10 and Mmp14 in monocytes, also Ccl3 in neutrophils, respectively. Mechanically, receptor-ligand interaction analysis identified the crosstalk of Cxcl10+/Mmp14+ monocytes with Ccl3+ neutrophils promoting fibrogenesis via coupling of HBEGF-CD44 and CSF1-CSF1R. In vivo, administration of clodronate liposomes, Cxcl10 or Mmp14 siRNA-loaded liposomes, Ccl3 receptor antagonist BX471, CD44 or CSF1R neutralizing antibodies significantly alleviated silica-induced lung fibrosis. Collectively, these results demonstrate that the newly defined Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils participate in the silicosis process and highlight anti-receptor-ligand pair treatment as a potentially effective therapeutic strategy in managing silicosis.

Ultra-fast supercritically solvothermal polymerization for large single-crystalline covalent organic frameworks.

Crystalline polymer materials, e.g., hyper-crosslinked polystyrene, conjugate microporous polymers and covalent organic frameworks, are used as catalyst carriers, organic electronic devices and molecular sieves. Their properties and applications are highly dependent on their crystallinity. An efficient polymerization strategy for the rapid preparation of highly or single-crystalline materials is beneficial not only to structure-property studies but also to practical applications. However, polymerization usually leads to the formation of amorphous or poorly crystalline products with small grain sizes. It has been a challenging task to efficiently and precisely assemble organic molecules into a single crystal through polymerization. To address this issue, we developed a supercritically solvothermal method that uses supercritical carbon dioxide (sc-CO2) as the reaction medium for polymerization. Sc-CO2 accelerates crystal growth due to its high diffusivity and low viscosity compared with traditional organic solvents. Six covalent organic frameworks with different topologies, linkages and crystal structures are synthesized by this method. The as-synthesized products feature polarized photoluminescence and second-harmonic generation, indicating their high-quality single-crystal nature. This method holds advantages such as rapid growth rate, high productivity, easy accessibility, industrial compatibility and environmental friendliness. In this protocol, we provide a step-by-step procedure including preparation of monomer dispersion, polymerization in sc-CO2, purification and characterization of the single crystals. By following this protocol, it takes 1-5 min to grow sub-mm-sized single crystals by polymerization. The procedure takes ~4 h from preparation of monomer dispersion and polymerization in sc-CO2 to purification and drying of the product.

Early Predictive Value of Different Indicators for Persistent Organ Failure in Acute Pancreatitis: A Systematic Review and Network Meta-Analysis.

GOALS: In this study, we conducted this network meta-analysis (based on the ANOVA model) to evaluate the predictive efficacy of each early predictor. BACKGROUND: Persistent organ failure (POF) is one of the determining factors in patients with acute pancreatitis (AP); however, the diagnosis of POF has a long-time lag (>48 h). It is of great clinical significance for the early noninvasive prediction of POF. STUDY: We conducted a comprehensive and systematic search in PubMed, Cochrane library, Embase, and Web of Science to identify relevant clinical trials, case-control studies, or cohort studies, extracted the early indicators of POF in studies, and summarized the predictive efficacy of each indicator through network meta-analysis. The diagnostic odds ratio (DOR) was used to rank the prediction efficiency of each indicator. RESULTS: We identified 23 studies in this network meta-analysis, including 10,393 patients with AP, of which 2014 patients had POF. A total of 10 early prediction indicators were extracted. The mean and 95% CI lower limit of each predictive indicator were greater than 1.0. Albumin had the largest diagnostic odds ratio, followed by high-density lipoprotein-cholesterol (HDL-C), Ranson Score, beside index for severity in acute pancreatitis Score, acute physiology and chronic health evaluation II, C-reactive protein (CRP), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Systemic Inflammatory Response Syndrome (SIRS) and blood urea nitrogen. CONCLUSIONS: Albumin, high-density lipoprotein-cholesterol, Ranson Score, and beside index for severity in acute pancreatitis Score are effective in the early prediction of POF in patients with AP, which can provide evidence for developing effective prediction systems. However, due to the limitations of the extraction method of predictive indicators in this study, some effective indicators may not be included in this meta-analysis.

Nuclear localization of Argonaute 2 is affected by cell density and may relieve repression by microRNAs.

Argonaute protein is associated with post-transcriptional control of cytoplasmic gene expression through miRNA-induced silencing complexes (miRISC). Specific cellular and environmental conditions can trigger AGO protein to accumulate in the nucleus. Localization of AGO is central to understanding miRNA action, yet the consequences of AGO being in the nucleus are undefined. We show nuclear enrichment of AGO2 in HCT116 cells grown in two-dimensional culture to high density, HCT116 cells grown in three-dimensional tumor spheroid culture, and human colon tumors. The shift in localization of AGO2 from cytoplasm to nucleus de-represses cytoplasmic AGO2-eCLIP targets that were candidates for canonical regulation by miRISC. Constitutive nuclear localization of AGO2 using an engineered nuclear localization signal increases cell migration. Critical RNAi factors also affect the localization of AGO2. Knocking out an enzyme essential for miRNA biogenesis, DROSHA, depletes mature miRNAs and restricts AGO2 localization to the cytoplasm, while knocking out the miRISC scaffolding protein, TNRC6, results in nuclear localization of AGO2. These data suggest that AGO2 localization and miRNA activity can be regulated depending on environmental conditions, expression of mature miRNAs, and expression of miRISC cofactors. Localization and expression of core miRISC protein machinery should be considered when investigating the roles of miRNAs.

Rapid and Accurate Detection of Marssonina coronariae in Apple Trees using Loop-Mediated Isothermal Amplification (LAMP).

Marssonina blotch of apple is a well-known plant disease caused by Marssonina coronariae, which can cause severe economic consequences. Due to the importance of early diagnosis for effective plant disease management, we aimed to develop a loop-mediated isothermal amplification (LAMP) assay that could rapidly detect M. coronariae in apple plants. The ribosomal DNA internal transcribed spacer (rDNA-ITS) sequence of M. coronariae was selected as the target for primer design. Our results showed optimal conditions for the LAMP reaction at 62℃ for 50 min, as indicated by color change and gel electrophoresis. The LAMP assay demonstrated specific discriminatory capability in differentiating M. coronariae from other pathogenic fungi in apple plants. In addition, the sensitivity tests revealed a detection limit of 100 fg µL-1 genomic DNA and 100 spores of M. coronariae for the LAMP assay. Finally, we successfully applied the LAMP assay to detect M. coronariae in apple leaf samples from the field. In general, our study provided a straightforward and efficient method for rapid diagnosis of apple blotch caused by M. coronariae, which could be applied in field condition and early occurrence of disease caused by M. coronariae could be detected.

CircZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and its translation function.

BACKGROUND: Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica. METHODS: We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of circZNF609, miR-145-5p, and KLF4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), Western blotting, immunofluorescence assays, and CCK8 were performed to investigate the role of the circZNF609/miR-145-5p/KLF4 axis and circZNF609-encoded peptides in fibroblast activation. RESULTS: Our data showed that circZNF609 was downregulated in activated fibroblasts and silica-induced fibrotic mouse lung tissues. Overexpression of circZNF609 could inhibit fibroblast activation induced by transforming growth factor-ß1 (TGF-ß1). Mechanically, we revealed that circZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and circZNF609-encoded peptides. Furthermore, circZNF609 was highly methylated and its expression was controlled by N6-methyladenosine (m6A) modification. Lastly, in vivo studies revealed that overexpression of circZNF609 attenuates silica-induced lung fibrosis in mice. CONCLUSIONS: Our data indicate that circZNF609 is a critical regulator of fibroblast activation and silica-induced lung fibrosis. The circZNF609 and its derived peptides may represent novel promising targets for the treatment of pulmonary fibrosis.

POEMS syndrome characterized by bone lesions: A case report.

RATIONALE: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes) syndrome is a rare clinical syndrome characterized by multiple peripheral neuropathies, hepatosplenomegaly, endocrine disorders, monoclonal paraproteinemia, and dermatosis. The main manifestations of POMES were nerve and skin changes, and bone disease was not reported. Here, we report a case of POEMS syndrome with the main manifestation of bone lesions. PATIENT CONCERNS: POMES is rare and its clinical manifestations are complex, making it difficult for patients to find the department they should visit. It is easy to miss diagnosis and misdiagnosis, delay the treatment time of patients, and affect the prognosis. DIAGNOSIS INTERVENTIONS: The patient was admitted to the gastroenterology department due to hepatic insufficiency. Multiple osteogenic changes were found by improved enhanced CT due to screening for causes of hepatic insufficiency, and spleen enlargement was indicated by abdominal ultrasound. Due to the involvement of multiple system problems, and follow-up of medical history, it was found that there was a history of discoloration of the distal limb in cold weather in the past 5 years. All things considered, it may be POMES. Further refinement of the bone marrow examination revealed active proliferation of granulocytes and erythrocytes. Bone marrow biopsy showed active hyperplasia, dominated by granulocytes. IFE showed IgA (type λ) and monoclonal myeloma (M) protein bands. To sum up, POMES diagnosis is considered. OUTCOMES: After the diagnosis is clear and the informed consent of the patient and his family is obtained, prednisone acetate is anti-inflammatory, lenalidomide is used to regulate immune function, liver and stomach protection treatment and bile secretion promotion are given. The patient reported improvement in liver function, significant improvement in overall and limb stiffness, and was discharged with improvement. LESSONS: Although bone lesions are not typically the main manifestation of POEMS syndrome, this diagnosis should be considered when this manifestation is combined with organ enlargement, skin changes, and peripheral neuropathy. In addition, the collection of medical history is crucial, when there is a clinical manifestation and auxiliary examination does not match, the idea should be expanded according to the relevant evidence, and finally make the corresponding diagnosis.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

A Rare Case of a Pancreatic Intraductal Oncocytic Papillary Neoplasm Associated With Invasive Adenocarcinoma Presenting as a Gastric Mass.

The World Health Organization recently recognized intraductal oncocytic papillary neoplasms of the pancreas (IOPNs) as distinct, pre-malignant pancreatic neoplasms. Due to their unique macroscopic and microscopic features, IOPNs are typically easy to diagnose and yield an indolent prognostic outcome. The diagnosis may be more complicated, and the prognosis may differ if an associated invasive carcinoma is present. Owing to the rarity of this entity, the available data is severely limited. Herein, we report a diagnostically challenging case of an IOPN associated with invasive carcinoma, initially presenting as a gastric mass with distinctive radiological and histopathological features.