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Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans. The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

During tumor expansion, breast cancer (BC) cells often experience reactive oxygen species accumulation and mitochondrial damage because of glucose shortage. However, the mechanism by which BC cells deal with the glucose-shortage-induced oxidative stress remains unclear. Here, we showed that MANF (mesencephalic astrocyte derived neurotrophic factor)-mediated mitophagy facilitates BC cell survival under glucose-starvation conditions. MANF-mediated mitophagy also promotes fatty acid oxidation in glucose-starved BC cells. Moreover, during glucose starvation, SENP1-mediated de-SUMOylation of MANF increases cytoplasmic MANF expression through the inhibition of MANF's nuclear translocation and hence renders mitochondrial distribution of MANF. MANF mediates mitophagy by binding to PRKN (parkin RBR E3 ubiquitin protein ligase), a key mitophagy regulator, in the mitochondria. Under conditions of glucose starvation, protein oxidation inhibits PRKN activity; nevertheless, the CXXC motif of MANF alleviates protein oxidation in RING II-domain of PRKN and restores its E3 ligase activity. Furthermore, MANF-PRKN interactions are essential for BC tumor growth and metastasis. High MANF expression predicts poor outcomes in patients with BC. Our results highlight the prosurvival role of MANF-mediated mitophagy in BC cells during glucose starvation, suggesting MANF as a potential therapeutic target. Abbreviation: 2DG, 2-deoxy-D-glucose; 5TG, 5-thio-D-glucose; ACSL4/FACL4, acyl-CoA synthetase long chain family member 4; Baf A1, bafilomycin A1; BRCA, breast cancer; CHX, cycloheximide; DMF, distant metastasis-free; DMFS, distant metastasis-free survival; ECM, extracellular matrix; ER, endoplasmic reticulum; ERS, endoplasmic reticulum stress; F-1,6-BP, fructose-1,6-bisphosphate; FAO, fatty acid oxidation; GSH, reduced glutathione; GSVA, gene set variation analysis; HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; IF, immunofluorescence; MANF, mesencephalic astrocyte derived neurotrophic factor; Mdivi-1, mitochondrial division inhibitor 1; MFI, mean fluorescence intensity; NAC, N-acetyl-L-cysteine; OCR, oxygen-consumption rate; OS, overall survival; PMI, SQSTM1/p62-mediated mitophagy inducer; PPP, pentose phosphate pathway; PRKN, parkin RBR E3 ubiquitin protein ligase; RBR, RING in between RING; RFS, relapse-free survival; ROS, reactive oxygen species; SAPLIPs, saposin-like proteins; TCGA, The Cancer Genome Atlas; TNBC, triple-negative breast cancer; WT, wild type. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta‐like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is analyzed using real‐time PCR, western blotting, and immunohistochemistry in BC patient specimens. Kaplan–Meier survival analysis is employed to assess its prognostic significance. Proteomic analysis, immunoprecipitation tests, and protein immunoblotting are employed to examine the impact of TBL2 on AKT phosphorylation activation. The findings reveal selective overexpression of TBL2 in BC, correlating significantly with various clinicopathological characteristics and poor survival outcomes in patients with BC. Through in vivo and in vitro experiments, it is observed that TBL2 suppression inhibits BC cell proliferation, while TBL2 overexpression has the opposite effect. Mechanistically, TBL2 is identified as a scaffolding protein that promotes PRMT5 and WDR77 interaction. This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment. [ABSTRACT FROM AUTHOR]

Background: Intranasal administration is a convenient route for drug delivery that can be applied for procedural sedation. However, there is currently limited exploration into fixed dosing regimens. This study was to investigate the pharmacokinetics (PK), pharmacodynamics (PD), bioavailability (BA) and safety of dexmedetomidine after fixed doses of intranasal and intravenous administration in healthy male and female subjects. Methods: Group A subjects received intranasal or intravenous administration in two periods (12 subjects received intranasal dexmedetomidine (Dex) or the intravenous formulation, and four received the corresponding placebo). Groups B to F underwent single-period dose ascending, receiving only the intranasal Dex formulation or the corresponding placebo (the number of subjects receiving the drug/placebo in groups B to F were 12/2, 12/2, 12/2, 10/2, 10/2, respectively), with doses of 75 μg, 125 μg, 150 μg, 175 μg, and 200 μg, respectively. After administration of each group, blood samples were collected to investigate the plasma concentration of dexmedetomidine, adrenaline and noradrenaline using a HPLC-MS/MS method. Ramsay score, blood pressure and heart rate were collected for safety evaluation. Pharmacokinetic parameters (Cmax, Tmax, AUC0-24h, AUC 0 – ∞ , and t1/2) of dexmedetomidine were calculated. Results: A total of 82 subjects were randomized. One subject withdrew for personal reasons before administration and the other subjects completed the entire study process. At a dose of 25 μg, the absolute bioavailability was 59%. Across the dose range of 25 to 200 μg, the median Tmax was similar (0.5–1 h), and the mean elimination half-life was comparable (3.09–4.28 h), with exposure (Cmax and AUC0-t) increasing with dose. The pharmacokinetics after intranasal spray administration exhibited linear characteristics, although Cmax was similar in the higher dose groups (175 μg and 200 μg). PD results showed that ideal sedation effects (Ramsay score of 3 or higher in at least 90% of subjects) could be achieved within 30 min following intranasal administration of 75 μg or higher doses. All the subjects were well tolerated without any serious adverse events (SAEs). Conclusion: Dexmedetomidine nasal spray was well tolerated and achieved satisfactory sedation in the dose range of 25–200 μg in Chinese healthy male and female subjects. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/, identifier CTR20201650 [ABSTRACT FROM AUTHOR]

This paper presents an event-triggered sliding mode fault-tolerant control method for networked control systems with actuator faults and external disturbance. First, an event-triggered scheme in the networked control systems is proposed to reduce the number of data transmission. In addition, considering the event-triggering, a sliding mode surface based on the system structure is constructed. Besides, to obtain the controller parameters that meet the H ∞ performance, the bounded real lemma in the form of linear matrix inequality is obtained using the Lyapunov functional. In addition, a sliding mode fault-tolerant control is designed to guarantee that the system can still run stably under the condition of faults and disturbances. Finally, the simulation results of gas turbine system are given to verify the feasibility of the theoretical method. [ABSTRACT FROM AUTHOR]

We developed and validated a sensitive, heart-cutting, two-dimensional liquid chromatography–tandem mass spectrometry (2D-LC‒MS/MS) method to determine the concentration of mometasone furoate in human plasma after nasal spray administration. Isotopically labeled mometasone furoate-13C,d6 was used as an internal standard (IS). Plasma samples were prepared using a solid-phase extraction (SPE) method. With this 2D-LC strategy, the analytes were trapped in the first dimension (1D) column, and only judiciously selected portions of the 1D effluent were transferred to the second dimension (2D) column for further separation to obtain high-resolution information. MS/MS quantification was performed in positive ionization mode via multiple-reaction monitoring (MRM). This analytical method was fully validated according to related regulatory guidance, and the results showed that the method is robust and sensitive enough for pharmacokinetic investigation of mometasone furoate with satisfactory linearity from 0.25 to 30 pg mL−1. This method was successfully applied to a bioequivalence (BE) study of mometasone furoate aqueous nasal sprays in healthy volunteers. [ABSTRACT FROM AUTHOR]

Mesoscale eddies are active in the Bay of Bengal and have profound effects on the dynamic conditions, the transport of heat and salt, and the primary productivity. We report a pair of periodic eddies in the Bay of Bengal and examine their characteristics, dynamic mechanisms and interannual variability based on satellite observations and a nonlinear 1.5‐layer reduced‐gravity model. The eddy pair mainly occupies the northwestern Bay of Bengal from March to May and consists of a cyclonic eddy in the north and an anticyclonic eddy in the south. The anticyclonic eddy is generated by local wind forcing, whereas the cyclonic eddy is significantly contributed by equatorial and coastal Kelvin waves. On an interannual scale, the eddy pair was exceptionally weak in 1999, 2000 and 2008 due to the extreme La Niña events in these years when the westerly wind anomaly over the equatorial Indian Ocean weakened the local wind forcing and coastal Kelvin waves. This study provides new knowledge on periodic eddies in the Bay of Bengal and advances our understanding of the dynamic connections between this marginal sea and the equator. Plain Language Summary: We report a pair of periodic eddies that occur almost annually in a fixed time period and position in the northwestern Bay of Bengal. We examine their characteristics and mechanism of generation and suggest that the eddy pair is related to local wind forcing and remote coastal Kelvin waves. We also show that the eddy pair was exceptionally weak during extreme La Niña events because the westerly wind anomaly weakened both the local wind stress and the remote coastal Kelvin waves. This study provides substantial evidence that equatorial dynamics have an important role in mesoscale eddies in marginal seas. Key Points: We report a pair of periodic eddies in the northwestern Bay of BengalThe eddy pair is induced by local wind forcing and remote coastal Kelvin waves via nonlinear processesThe eddy pair was exceptionally weak in 1999, 2000 and 2008 due to the westerly wind anomaly over the equatorial Indian Ocean [ABSTRACT FROM AUTHOR]

Climate change and public health emergencies have severely threatened world food security. In response, the Chinese government has actively promoted sustainable agricultural practices (SAPs) and emphasized the importance of integrated packages to enhance the development of high-quality agriculture. However, due to information failure, farmers' adoption rate of SAPs is still very low. Meanwhile, internet use can effectively reduce the cost of information barriers and catalyze farmers to promote the joint adoption of SAPs. This paper aims to theoretically elucidate the logic of how internet use impacts farmers' joint adoption of SAPs. Empirical analysis based on data from 844 rice farmers in southern China reveals that internet use can significantly promote the joint adoption of SAPs, and adoption behaviours are complementary across multiple technologies. Furthermore, internet use in the group of rice farmers with more farmlands or those receiving subsidies is more inclined to adopt SAPs jointly. These findings suggest that developing countries should prioritize public investment in rural internet infrastructure to facilitate joint adoption of SAPs through farmers' internet use. The moderate scale of farmland usage and targeted agricultural subsidy policies can further enhance the effectiveness of ICT-based joint adoption of SAPs. [ABSTRACT FROM AUTHOR]

Urban agriculture has been seen as an essential strategy for enhancing food security and urban resilience and is valued by many countries, but its development faces many challenges. Whether farmland system reform can improve the factor allocation of urban farmer households and then promote the resilience of urban agriculture has not received sufficient attention. Therefore, this article uses property rights theory to explain the logic that farmland titling as a formal institution affects the factor allocation of urban farmer households (UFHs). Furthermore, empirical analysis of whether farmland titling positively affects the UFHs' willingness toward farmland, and capital allocation was performed based on household-level survey data from metropolitan Guangzhou, China. The implications of this research are as follows: emphasizing that the reform of farmland titling is vital for the farmland transaction market, strengthening talent cultivation, and increasing agricultural green input and investment, all of which are beneficial to promote the modernization and sustainability of urban agriculture, thus improving the resilience of urban regions. [ABSTRACT FROM AUTHOR]

Background: Host immunity plays an important role in tumor development and treatment. Tumor‐infiltrating lymphocytes (TILs) have been proven to predict the efficacy of neoadjuvant therapy (NAT) in breast cancer (BC) patients, but their application is limited due to various reasons. This study aims to explore the relationship between peripheral blood lymphocytes (PBLs) subsets distribution and the efficacy of NAT. Methods: Between December 2017 and March 2021, a total of 116 BC patients appropriate for NAT in Sun Yat‐Sen University cancer center were enrolled, pre‐NAC baseline blood samples were taken for further flow cytometry analysis to quantitatively evaluate the PBLs subsets distribution, and corresponding clinical information including pathological complete response (pCR) rate of NAT response were recorded. Results: Baseline CD3+ T cells(OR 1.11, 1.03–1.21, p = 0.011), CD8+ T cells (OR 1.09, 1.02–1.18, p = 0.015), and NK cells (OR 0.91, 0.83–0.98, p = 0.028) in PBLs subgroup distribution were independent predictors of pCR in BC patients receiving NAT, in which CD8+ T cells had the highest predictive ability (AUC = 0.76). Compared with some previous prediction indicators, its prediction ability has been improved to some extent. Conclusion: Peripheral baseline CD3+ T cells, CD8+ T cells, and NK cells were independent predictors of pCR in BC patients receiving NAT, in which CD8+ T cells had the highest predictive ability. Therefore, it can provide newly non‐invasive, relatively accurate and easily accessible predictors for corresponding patients, and help clinicians better understand tumor immunity. [ABSTRACT FROM AUTHOR]

Purpose: The authors aimed to evaluate the prognostic and predictive value of androgen receptor (AR) expression in patients with luminal/human EGFR2 negative (HER2-) T1N0 breast cancer. Methods: The cohort in this retrospective study comprised 471 patients with luminal/HER2- T1N0 breast cancer who had undergone surgery between 2013 and 2017 in the authors' center. Results: AR+ tumors were associated with favorable characteristics. AR+ patients had better 5-year recurrence-free survival rates and the risk of recurrence was greater for AR- than for AR+ patients. AR- status predicted the failure of adjuvant endocrine therapy with aromatase inhibitors and of adjuvant chemotherapy with docetaxel plus cyclophosphamide. Conclusion: AR+ expression is significantly related to a better prognosis. AR expression may be an additional biomarker for both endocrine and chemotherapy responsiveness. [ABSTRACT FROM AUTHOR]

UV/chlorine treatment is an efficient technology for removing organic pollutants in wastewater. Nevertheless, degradation of antihistamines in the UV/chlorine system, especially the underlying reaction mechanism, is not yet clear. In this study, the degradation of cetirizine (CTZ), a representative antihistamine, under UV/chlorine treatment was investigated. The results showed that CTZ could undergo fast degradation in the UV/chlorine system with an observed reaction rate constant (kobs) of (0.19 ± 0.01) min−1, which showed a first-increase and then-decrease trend with its initial concentration increased. The degradation of CTZ during the UV/chlorine treatment was attributed to direct UV irradiation (38.7%), HO• (35.3%), Cl• (7.3%), and ClO• (17.1%). The kobs of CTZ decreased with the increase in pH and the increase in concentrations of a representative dissolved organic matter, Suwannee River natural organic matter (SRNOM), due to their negative effects on the concentrations of reactive species generated in the UV/chlorine system. The detailed reaction pathways of HO•, ClO•, and Cl• with CTZ were revealed using quantum chemical calculation. This study provided significant insights into the efficient degradation and the underlying mechanism for the removal of CTZ in the UV/chlorine system. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer-related deaths in women. The purpose of this study was to develop a prognostic model based on BC-related DNA methylation pattern. A total of 361 BC incidence-related probes (BCIPs) were differentially methylated in blood samples from women at high risk of BC and BC tissues. Twenty-nine of the 361 BCIPs that significantly correlated with BC outcomes were selected to establish the BCIP score. BCIP scores based on BC-related DNA methylation pattern were developed to evaluate the mortality risk of BC. The correlation between overall survival and BCIP scores was assessed using Kaplan–Meier, univariate, and multivariate analyses. In BC, the BCIP score was significantly correlated with malignant BC characteristics and poor outcomes. Furthermore, we assessed the BCIP score-related gene expression profile and observed that genes with expressions associated with the BCIP score were involved in the process of cancer immunity according to GO and KEGG analyses. Using the ESTIMATE and CIBERSORT algorithms, we discovered that BCIP scores were negatively correlated with both T cell infiltration and immune checkpoint inhibitor response markers in BC tissues. Finally, a nomogram comprising the BCIP score and BC prognostic factors was used to establish a prognostic model for patients with BC, while C-index and calibration curves were used to evaluate the effectiveness of the nomogram. A nomogram comprising the BCIP score, tumor size, lymph node status, and molecular subtype was developed to quantify the survival probability of patients with BC. Collectively, our study developed the BCIP score, which correlated with poor outcomes in BC, to portray the variation in DNA methylation pattern related to BC incidence. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is fast‐growing and highly metastatic with the poorest prognosis among the breast cancer subtypes. Inactivation of glycogen synthase kinase 3 beta (GSK3β) plays a vital role in the aggressiveness of TNBC; however, the underlying mechanism for sustained GSK3β inhibition remains largely unknown. Here, we find that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) is upregulated in TNBC and relevant to poor prognosis in patients. Overexpression of PPP1R14C facilitates cell proliferation and the aggressive phenotype of TNBC cells, whereas the depletion of PPP1R14C elicits opposite effects. Moreover, PPP1R14C is phosphorylated and activated by protein kinase C iota (PRKCI) at Thr73. p‐PPP1R14C then represses Ser/Thr protein phosphatase type 1 (PP1) to retain GSK3β phosphorylation at high levels. Furthermore, p‐PPP1R14C recruits E3 ligase, TRIM25, toward the ubiquitylation and degradation of non‐phosphorylated GSK3β. Importantly, the blockade of PPP1R14C phosphorylation inhibits xenograft tumorigenesis and lung metastasis of TNBC cells. These findings provide a novel mechanism for sustained GSK3β inactivation in TNBC and suggest that PPP1R14C might be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is not sensitive to targeted therapy with HER-2 monoclonal antibody and endocrine therapy due to lack of ER, PR, and HER-2 receptors. TNBC is a breast cancer subtype with the worst prognosis and the highest mortality rate compared with other subtypes. Materials and Methods: Breast cancer-related data were retrieved from The Cancer Genome Atlas (TCGA) database, and 116 cases of triple-negative breast cancer were identified from the data. GSE31519 dataset was retrieved from Gene Expression Omnibus (GEO) database, comprising a total of 68 cases with TNBC. Survival analysis was performed based on immune score, infiltration score and mutation score to explore differences in prognosis of different immune types. Analysis of differentially expressed genes was conducted and GSEA analysis based on these genes was conducted to explore the potential mechanism. Results: The findings showed that comprehensive immune typing is highly effective and accurate in assessing prognosis of TNBC patients. Analysis showed that MMP9, CXCL9, CXCL10, CXCL11 and CD7 are key genes that may affect immune typing of TNBC patients and play an important role in prediction of prognosis in TNBC patients. Conclusion: The current study presents an evaluation system based on immunophenotyping, which provides a more accurate prognostic evaluation tool for TNBC patients. Differentially expressed genes can be targeted to improve treatment of TNBC. [ABSTRACT FROM AUTHOR]

Although the tumor microenvironment (TME) plays an important role in the development of many cancers, its roles in breast cancer, especially triple-negative breast cancer (TNBC), are not well studied. This study aimed to identify genes related to the TME and prognosis of TNBC. Firstly, we identified differentially expressed genes (DEG) in the TME of TNBC, using Expression data (ESTIMATE) datasets obtained from the Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues. Next, survival analysis was performed to analyze the relationship between TME and prognosis of TNBC, as well as determine DEGs. Genes showing significant differences were scored as alternative genes. A protein-protein interaction (PPI) network was constructed and functional enrichment analysis conducted using the DEG. Proteins with a degree greater than 5 and 10 in the PPI network correspond with hub genes and key genes, respectively. Finally, CCR2 and CCR5 were identified as key genes in TME and prognosis of TNBC. Finally, these results were verified using Gene Expression Omnibus (GEO) datasets and immunohistochemistry of TNBC patients. In conclusion, CCR2 and CCR5 are key genes in the TME and prognosis of TNBC with the potential of prognostic biomarkers in TNBC. [ABSTRACT FROM AUTHOR]

Background: Vacuum drains have been extensively applied to prevent seroma formation after breast surgery. However, the usage of negative suction drainage is mainly determined by surgeon's experience and preferences. The aim of this study is to prospectively compare the drain effect after breast surgery between the low and high vacuum drains. Methods: This prospectively randomized trial (from January 2018 to June 2019) involved 188 patients who were subjected to modified radical mastectomy (group A, n=128) or immediate breast reconstruction with implants (group B, n=60). In each group, patients were randomized to receive high vacuum drain (pressure=– 98 kPa) or low vacuum drain (pressure=– 12 kPa) after surgery. Days of drain permanence, which means the duration of drainage, was the primary endpoint. Results: According to the comparison of days of drain permanence, the effect of a low vacuum drain is not inferior to a high vacuum drain in group A (pectoral drain, P< 0.001; axillary drain, P< 0.001) or group B (submuscular drain, P=0.002). The complications frequently occurred on patients with high vacuum drain (11.7%), such as seroma formation. The expense of low vacuum drain was significantly lower than high vacuum drain in both groups (P< 0.01). Conclusion: The drain effect of the low vacuum drain is not inferior to a high vacuum drain in both group A and group B. The low vacuum drain was effective, relatively cheap, and did not increase the incidence of complications; it is therefore more recommended after breast surgery. [ABSTRACT FROM AUTHOR]

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Background: Gastric cancer (GC) accounts for the fourth most occurring malignancy and the third major cause of cancer death. Identifying novel molecular signaling pathways participating in gastric tumorigenesis and progression is pivotal for rational design of targeted therapies to improve advanced GC outcome. Recently, the endoplasmic reticulum (ER) protein 29 (ERp29) has been shown to inversely associate with primary tumor development and function as a tumor suppressor in breast cancer. However, the role of ERp29 in GC patients' prognosis and its function in GC progression is unknown.Methods: Clinical importance of ERp29 in the prognosis of GC patients was assessed by examining its expression in 148 GC tumor samples and correlation with clinicopathological characteristics and survival of the patients. The function and underlying mechanisms of ERp29 in GC growth, invasion and metastasis were explored both in vitro and in vivo.Results: Downregulation of ERp29 was commonly found in GC tissues and highly correlated with more aggressive phenotypes and poorer prognosis. Functional assays demonstrated that knockdown of ERp29 increased GC cell migration and invasion and promoted metastasis. Conversely, ectopic overexpression of ERp29 produced opposite effects. Mechanistic studies revealed that loss of ERp29 induced an epithelial-to-mesenchymal transition (EMT) in the GC cells through activation of PI3K/Akt pathway signaling.Conclusion: These findings suggest that downregulation of ERp29 is probably one of the key molecular mechanisms responsible for the development and progression of GC. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to develop an ultrasonographic scoring model for staging hypofunction of salivary glands (SGs) in patients with Sjögren disease (SjD)., Methods: The assessment of SG secretory hypofunction was conducted by measuring whole salivary flows. B-mode ultrasonography was performed bilaterally on the parotid and submandibular glands to quantitatively evaluate the gland score and Outcome Measures in Rheumatology (OMERACT) score. The correlation between these scores and SG secretory function in patients with SjD was analyzed, leading to the development of an ultrasonographic scoring model for staging SG hypofunction., Results: A 1-center derivation cohort comprising 164 patients with SjD and a double-center validation cohort consisting of 107 patients with SjD were included. Both ultrasonographic scores demonstrated excellent discriminatory ability between patients with SjD with hypofunction and those with normal function (area under the curve > 0.8 for both; P < 0.001). A novel ultrasonographic scoring model revealed that low total OMERACT scores (< 5) indicated initial-stage SG hypofunction, whereas high scores (> 9) suggested end-stage hypofunction. Conversely, patients with moderate-level total OMERACT scores (5-9) required further stratification using total gland scores. The incidence of SG hypofunction among all 271 patients with SjD was found to be 18% in the initial stage, 58% in the progressive stage, and 100% in the end stage ( P < 0.01). Further, the incidence of lacrimal gland involvement and hyperglobulinemia (IgG > 16 IU/mL) was significantly lower in the initial-stage patients compared to those at other stages (all P < 0.01)., Conclusion: The novel ultrasonographic scoring model incorporates precise definitions for each stage of SG hypofunction, providing a robust and clinically significant approach to stratification of SG secretory hypofunction in SjD.

Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of breast cancer, and there is no effective treatment other than chemotherapy. Processing of precursors 1 (POP1) is the most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, the role of POP1 in TNBC remains clarified. A series of molecular biological experiments in vitro and in vivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC. Here, we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis. We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo. Mechanistically, POP1 directly binds to the coding sequence (CDS) region of CDKN1A mRNA and degrades it. The degradation process depends on the N6-methyladenosine (m6A) modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Moreover, the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel. In summary, our findings reveal the pivotal role of POP1 in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Chao Zhang et al.)

Background: The systemic inflammation response index (SIRI) has been reported to associate with survival outcomes in breast cancer patients. However, the effects of baseline SIRI and SIRI change after neoadjuvant chemotherapy (NACT) have not been thoroughly investigated. This study aimed to evaluate the role of baseline SIRI and SIRI change after NACT in predicting survival outcomes, and establish a nomogram based on SIRI., Methods: A total of 260 patients diagnosed with breast cancer who received NACT between January 2014 and December 2018 at our hospital were included. The clinical data were retrospectively collected from the medical records management system. The associations between clinicopathological factors and baseline SIRI, pathological complete response (pCR) were analyzed by Student's t -test, Chi-squared test, or Fisher's exact test. The association between clinicopathological factors and disease-free survival (DFS) was evaluated by univariate and multivariate Cox regression analyses., Results: Patients with a tumor-node-metastasis (TNM) stage of I, II, and III were 1.9%, 20.0%, and 78.1% respectively. The median follow-up time was 40 months, and 74 (28.5%) patients had cancer recurrence during the follow-up. Both in the univariate and multivariate analysis, Ki-67, pCR, and baseline SIRI were independent factors associated with DFS. Patients with low baseline SIRI had prolonged DFS compared with those with high baseline SIRI [≤1.6×10 9 vs. >1.6×10 9 , hazard ratio (HR) =0.545, P=0.028]. In addition, SIRI change after NACT was also an independent factor associated with DFS, and patients with minor SIRI change had longer DFS than patients with major SIRI change (>50% or <-30% vs. ≤50% and ≥-30%, HR =1.721, P=0.037). Nomograms were established based on Ki-67, pCR, and baseline SIRI or SIRI change after NACT with a concordance index of 0.665 and 0.663 respectively, and the nomogram provided a convenient tool for predicting the probability of DFS., Conclusions: The baseline SIRI and SIRI change after NACT could act as potential biomarkers for predicting survival outcomes in breast cancer. Besides, the nomogram with SIRI is an economic and convenient tool for predicting DFS. Larger prospective studies are needed to verify the results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-226/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Introduction: Compared to other types of breast cancer, triple-negative breast cancer (TNBC) does not effectively respond to hormone therapy and HER2 targeted therapy, showing a poor prognosis. There are currently a limited number of immunotherapeutic drugs available for TNBC, a field that requires additional development., Methods: Co-expressing genes with M2 macrophages were analyzed based on the infiltration of M2 macrophages in TNBC and the sequencing data in The Cancer Genome Atlas (TCGA) database. Consequently, the influence of these genes on the prognoses of TNBC patients was analyzed. GO analysis and KEGG analysis were performed for exploring potential signal pathways. Lasso regression analysis was conducted for model construction. The TNBC patients were scored by the model, and patients were divided into high- and low-risk groups. Subsequently, the accuracy of model was further verified using GEO database and patients information from the Cancer Center of Sun Yat-sen University. On this basis, we analyzed the accuracy of prognosis prediction, correlation with immune checkpoint, and immunotherapy drug sensitivity in different groups., Results: Our findings revealed that OLFML2B, MS4A7, SPARC, POSTN, THY1, and CD300C genes significantly influenced the prognosis of TNBC. Moreover, MS4A7, SPARC, and CD300C were finally determined for model construction, and the model showed good accuracy in prognosis prediction. And 50 immunotherapy drugs with therapeutic significance in different groups were screened, which were assessed possible immunotherapeutics that have potential application and demonstrated the high precision of our prognostic model for predictive analysis., Conclusion: MS4A7, SPARC, and CD300C, the three main genes used in our prognostic model, offer good precision and clinical application potential. Fifty immune medications were assessed for their ability to predict immunotherapy drugs, providing a novel approach to immunotherapy for TNBC patients and a more reliable foundation for applying drugs in subsequent treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Feng, Zhong, Zouxu, Xiong, Huang, Zhang, Wang and Yi.)