MiR-34a promotes mitochondrial pathway of apoptosis in human salivary gland epithelial cells by activating NF-κB signaling.

To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.

γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway.

INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

Mutual regulation of PD-L1 immunosuppression between tumor-associated macrophages and tumor cells: a critical role for exosomes.

Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart the anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through the direct interaction of PD-L1 with PD-1 on T lymphocyte surfaces. Recent research focusing on the tumor microenvironment has illuminated the pivotal role of immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated immunosuppression. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. In addition to receiving signals from tumor-derived exosomes that promote PD-L1 expression, TAMs also exert control over PD-L1 expression in tumor cells through the release of exosomes. This paper aims to summarize the mechanisms by which exosomes participate in this process, identify crucial factors that influence these mechanisms, and explore innovative strategies for inhibiting or reversing the tumor-promoting effects of TAMs by targeting exosomes.

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial.

BACKGROUND: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC. METHODS: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed. RESULTS: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%). CONCLUSION: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC. REGISTRATION NUMBER: ChiCTR1800019421.

Neoadjuvant PD-1 blockade combined with chemotherapy is not superior to neoadjuvant chemotherapy alone in resectable locally advanced esophageal carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy followed by surgery has been recommended as standard treatment in patients with locally advanced esophageal cancer (LAEC). But the risk of tumor recurrence still remained, and many patients refused or abandoned radiotherapy because of the intolerable adverse effects in China. Neoadjuvant immunochemotherapy (nICT) followed by surgery has become an emerging treatment in patients with esophageal cancer. There was still no consensus on whether nICT was superior to nCT alone in patients with esophageal cancer. METHODS: In this retrospective study, patients with resectable esophageal cancer who received surgery after nICT (n=26, 40%) or nCT alone (n=39, 60%) were included. The patients were classified as nICT or nCT arm. The primary endpoints were pathological tumor response (PTR) and event-free survival (EFS). The different clinic-pathological features were compared by the Kruskal-Wallis test for continuous variables and the Chi-square (χ2) test for categorical variables. Kaplan-Meier curves were used to estimate EFS from the date of treatment to recurrence or death. All tests were 2-sided with a significative P-value defined <.05. RESULTS: Three (11.5%) of the 26 patients achieved pathological complete remission (pCR) in the nICT group, and four (10.3%) of the 39 patients achieved pCR in the nCT group, respectively (P=1.000). Six (23.1%) of the 26 patients achieved major pathological response (MPR) in the nICT group, and 11 (28.2%) of the 39 patients achieved MPR in the nCT group, respectively (P=0.645). Downstaging was achieved in 13 (44.8%) patients in the nICT group and 16 (55.2%) patients in the nCT group, respectively (P=0.732). To verify the tumor regression grade (TRG) results, we compared them with MPR and pCR, which showed a significant dependency (P< 0.001). Patients who achieved downgrading showed better MPR and pCR rates (P<0.001 and P =0.010). There was no significant difference in EFS between the nICT and nCT groups (HR=1.011, 95% CI: 0.421-2.425, P = 0.981). CONCLUSIONS: Neoadjuvant PD-1 blockade combined with chemotherapy was not superior to chemotherapy alone for patients with resectable locally advanced esophageal carcinoma. However, more studies with long-term follow-up were needed to confirm this result.

Methyltransferase SETD2 inhibits tumor growth and metastasis via STAT1-IL-8 signaling-mediated epithelial-mesenchymal transition in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a major subtype of non-small-cell lung cancer, which is the leading cause of cancer death worldwide. The histone H3K36 methyltransferase SETD2 has been reported to be frequently mutated or deleted in types of human cancer. However, the functions of SETD2 in tumor growth and metastasis in LUAD has not been well illustrated. Here, we found that SETD2 was significantly downregulated in human lung cancer and greatly impaired proliferation, migration, and invasion in vitro and in vivo. Furthermore, we found that SETD2 overexpression significantly attenuated the epithelial-mesenchymal transition (EMT) of LUAD cells. RNA-seq analysis identified differentially expressed transcripts that showed an elevated level of interleukin 8 (IL-8) in STED2-knockdown LUAD cells, which was further verified using qPCR, western blot, and promoter luciferase report assay. Mechanically, SETD2-mediated H3K36me3 prevented assembly of Stat1 on the IL-8 promoter and contributed to the inhibition of tumorigenesis in LUAD. Our findings highlight the suppressive role of SETD2/H3K36me3 in cell proliferation, migration, invasion, and EMT during LUAD carcinogenesis, via regulation of the STAT1-IL-8 signaling pathway. Therefore, our studies on the molecular mechanism of SETD2 will advance our understanding of epigenetic dysregulation at LUAD progression.

Successful salvage therapy using high-dose furmonertinib (AST2818) for non-small-cell lung cancer after Osimertinib resistance: a case report.

Osimertinib, the third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, responds well to advanced non-small-cell lung cancer (NSCLC) with the EGFR T790M mutation. However, resistance to osimertinib would inevitably occur. We report a case of an advanced NSCLC patient after osimertinib resistance who was successfully treated by high-dose furmonertinib (AST2818) at 160 mg. The patient initially received the GCP regimen for 11 months and displayed partial response. The patient received osimertinib 80 mg at the time of progression with a stable clinical and radiological response lasting only 7 months. Subsequently, she was commenced on furmonertinib 160 mg once daily. After 2 weeks of furmonertinib, the patient's tumor was markedly smaller on a follow-up chest CT scan, and her respiratory symptoms also improved. What shocked us was that after a month's re-examination of the cranial MRI, the intracranial lesions wholly disappeared. This report provides a case of the successful rescue of osimertinib-resistant NSCLC patients by oral administration of high-dose furmonertinib 160 mg daily, providing a new treatment option for osimertinib-resistant patients.

Silencing of long non-coding RNA KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in childhood pneumonia.

PURPOSE: Long non-coding RNAs (lncRNAs) play important roles in the development of pneumonia. We aimed to explore the role of the lncRNA KCNQ1OT1 in pneumonia and its underlying mechanisms. METHODS: The expression of KCNQ1OT1, FOXM1, and miR-370-3p was detected in the serum of 24 children with pneumonia and in 24 healthy controls. Normal human embryonic lung-derived diploid fibroblasts (WI-38 cells) were stimulated with LPS (10 µg/mL) to simulate the cellular model of pneumonia, and cell viability, apoptosis, and inflammation were analysed. Dual luciferase reporter and/or RNA binding protein immunoprecipitation assays were performed to test the relationship between miR-370-3p and KCNQ1OT1/FOXM1. Mice were intratracheally administered LPS (5 mg/kg) to induce an in vivo model of pneumonia, and pathological injury and inflammation were analysed. RESULTS: The expression of KCNQ1OT1 and FOXM1 was up-regulated, and miR-370-3p was down-regulated in the serum of children with pneumonia, LPS-treated WI-38 cells, and in lung tissues of LPS-treated mice. Silencing of KCNQ1OT1 or overexpression of miR-370-3p suppressed cell apoptosis and inflammation and facilitated cell viability in LPS-treated WI-38 cells. KCNQ1OT1 directly targets miR-370-3p and negatively regulates its expression. FOXM1 was targeted by miR-370-3p and negatively modulated by miR-370-3p. In addition, silencing of KCNQ1OT1 mitigated LPS-induced lung injury and inflammation in mice. The protective effects of KCNQ1OT1 silencing in LPS-treated WI-38 cells and mice were reversed by silencing of miR-370-3p or overexpression of FOXM1. CONCLUSION: Silencing of KCNQ1OT1 alleviates LPS-induced lung injury by regulating the miR-370-3p/FOXM1 axis in pneumonia.

Evaluation of neuropsychiatric comorbidities and their clinical characteristics in Chinese children with asthma using the MINI kid tool.

BACKGROUND: The mental health and quality of life in children with asthma have attracted widespread attention. This study focused on the evaluation of mental health conditions and their clinical characteristics in Chinese children with asthma. METHODS: A total of 261 children with asthma aged 6 to 16 years old and 261 age- and gender-matched children from the general population were recruited to participate in this study from Guizhou Provincial People's Hospital. The parents of all subjects were interviewed using the MINI Kid and were required to finish a clinical characteristics questionnaire. Logistic regression analysis was performed to evaluate risk factors. RESULTS: The prevalence of mental health conditions in the asthma group was significantly higher than that in the control group (26.4% vs 14.6%, P < 0.001). A total of 10 mental health conditions was identified in the asthma group, the most common of which was ADHD (11.5%; 30/261), followed by oppositional defiant disorder (ODD) (10.7%; 28/261), separation anxiety disorder (6.1%; 16/261), social anxiety disorder (3.8%; 10/261), specific phobias (2.3%; 6/261), agoraphobia without panic (1.5%; 4/261), (mild) manic episodes (1.1%; 3/261), major depressive episodes (MDEs) (0.8%; 2/261), movement (tic) disorder (0.8%; 2/261), and dysthymia (0.4%; 1/261). A total of 6 neuropsychiatric conditions was detected in the control group, including ODD (5.7%; 15/261), ADHD (4.6%; 12/261), social anxiety disorder (3.1%; 8/261), seasonal anxiety disorder (SAD) (2.3%; 6/261), specific phobias (1.1%; 3/261), and agoraphobia without panic (0.4%; 1/261). The prevalence rates of ODD, ADHD, and SAD differed significantly between the two groups (P < 0.05). Multiple regression analysis revealed that severe persistent asthma (OR = 3.077, 95% CI 1.286-7.361), poor asthma control (OR = 2.005, 95% CI 1.111-3.619), and having asthma for > 3 years (OR = 2.948, 95% CI 1.580-5.502) were independent risk factors for the presence of mental health conditions in asthmatic children. CONCLUSIONS: Children with asthma have a higher rate of mental health conditions than non-asthmatic children. Standardized diagnosis and treatment may help reduce the risk of neuropsychiatric conditions.

PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation.

Immunotherapy has become a crucial modality for non-small-cell lung cancer treatment. Recently, two immune checkpoints, PD-1 and PD-L1, have emerged as important targets for immunotherapy. Their antitumor efficacy has been confirmed by in vitro and in vivo studies. But the correlation between PD-1/PD-L1 expression and EGFR expression was controversial and needs more evidences to support the combination of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors.

Report of clinical studies on chronochemotherapy for advanced non-small cell lung cancer in China.

Chronochemotherapy has been proposed as a promising modality to provide timely optimized medication to achieve maximum efficacy with minimum side effect for patients with non-small cell lung cancer for years. We collected the data of 11 clinical studies performed in China with the purpose to compare the difference between chronochemotherapy and traditional chemotherapy. Results showed that chronochemotherapy has a more favorable efficacy and safety than traditional chemotherapy.

Clinical significance of serum ferritin in elderly patients with primary lung carcinoma.

This study determined the levels of serum ferritin (SF) and carcinoembryonic antigen (CEA) in elderly patients with advanced primary lung cancer (PLC), and aimed to investigate the correlation between the SF level and clinical characteristics and compare the positive rates of SF and CEA levels in PLC patients and those in normal subjects. The SF and CEA levels of 69 elderly cases of advanced PLC and 63 elderly controls were determined by electrochemiluminescence method. The correlation between each independent clinicopathological characteristic and levels of SF and CEA was calculated. The positive rates of SF and CEA levels in PLC patients and those in normal subjects were compared. The results revealed that the level of SF in controls was significantly lower than those in patients with advanced LC (145.04 ± 141.77 vs. 293.57 ± 274.95 ng/ml, t = -3.845, P = 0.000). There was a statistically significant difference between SF level and gender, smoking, and regional lymph node metastasis, respectively (P < 0.05). The positive rate of SF combining with CEA was significantly higher than those of SF and CEA alone in patients with advanced PLC. High serum level of SF is helpful for diagnosing PLC in elderly patients and indicates poor prognosis.

CD40 mutant expression and its clinical significance to prognosis in gastric cancer patients.

BACKGROUND: We aimed to detect CD40 mutant expression and evaluate its clinical significance in gastric cancer. METHODS: CD40 mutant expression in 78 cases of gastric cancer tissues, 10 cases of normal gastric tissues, and 10 cases of gastric adenoma tissues by immunohistochemical test. Survival analyses were also performed. RESULTS: The positive CD40 mutant rate in gastric cancer was 55.1% (43/78). No positive CD40 mutant staining was observed in the normal gastric tissue or the gastric adenoma. CD40 mutants expression was significantly correlated with invasive depth, lymph metastasis, and TNM stage (P <0.05). Cases with negative CD40 mutant expression had a significantly longer median survival time than those with positive CD40 mutant expression (40 vs. 14 months, P <0.05). A lower death risk in negative CD40 mutant cases was observed comparing with positive CD40 mutant cases. CONCLUSIONS: Positive CD40 mutant expression suggests a poorer prognosis of gastric cancer cases.

Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer.

BACKGROUND: B7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer. METHODS: Blood specimens from 132 patients with gastric cancer and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent assay. RESULTS: Median concentrations of sB7-H4 in patients with gastric cancer were significantly higher than those in healthy volunteers (16.85 versus 10.46 ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node-metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001, respectively), but not with sex, age, tumor location or histological subtype (all P >0.05). Additionally, the overall survival rate was significantly lower in patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0% versus 77.3%, χ2 = 10.78, P = 0.001). Moreover, multivariate analysis demonstrated that the risk of death was significantly higher in patients with high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039). CONCLUSIONS: sB7-H4 is a valuable blood marker for predicting the progression and prognosis of patients with gastric cancer.

Vegetation canopy structure mediates the response of gross primary production to environmental drivers across multiple temporal scales.

Gross primary production (GPP) is a critical component of the global carbon cycle and plays a significant role in the terrestrial carbon budget. The impact of environmental factors on GPP can occur through both direct (by influencing photosynthetic efficiency) and indirect (through the modulation of vegetation structure) pathways, but the extent to which these mechanisms contribute has been seldom quantified. In this study, we used structural equation modeling and observations from the FLUXNET network to investigate the direct and indirect effects of environmental factors on terrestrial ecosystem GPP at multiple temporal scales. We found that canopy structure, represented by leaf area index (LAI), is a crucial intermediate factor in the GPP response to environmental drivers. Environmental factors affect GPP indirectly by altering canopy structure, and the relative proportion of indirect effects decreased with increasing LAI. The study also identified different effects of environmental factors on GPP across time scales. At the half-hourly time scale, radiation was the primary driver of GPP. In contrast, the influences of temperature and vapor pressure deficit took on greater prominence at longer time scales. About half of the total effect of temperature on GPP was indirect through the regulation of canopy structure, and the indirect effect increased with increasing time scale (GPPNT-based models: 0.135 (half-hourly) vs. 0.171 (daily) vs. 0.189 (weekly) vs. 0.217 (monthly); GPPDT-based models: 0.139 vs. 0.170 vs. 0.187 vs. 0.215; all values were reported in gC m-2 d-1 °C-1, P < 0.001); while the indirect effect of radiation on GPP was comparatively lower, accounting for less than a quarter of the total effect. Furthermore, we observed a direct, negative-to-positive impact of precipitation on GPP across timescales. These findings provide crucial information on the interplay between environmental factors and LAI on GPP and enable a deeper understanding of the driving mechanisms of GPP.

A global dataset of the fraction of absorbed photosynthetically active radiation for 1982-2022.

The fraction of absorbed photosynthetically active radiation (FPAR) is an essential biophysical parameter that characterizes the structure and function of terrestrial ecosystems. Despite the extensive utilization of several satellite-derived FPAR products, notable temporal inconsistencies within each product have been underscored. Here, the new generation of the GIMMS FPAR product, GIMMS FPAR4g, was developed using a combination of a machine learning algorithm and a pixel-wise multi-sensor records integration approach. PKU GIMMS NDVI, which eliminates the orbital drift and sensor degradation issues, was used as the data source. Comparisons with ground-based measurements indicate root mean square errors ranging from 0.10 to 0.14 with R-squared ranging from 0.73 to 0.87. More importantly, our product demonstrates remarkable spatiotemporal coherence and continuity, revealing a persistent terrestrial darkening over the past four decades (0.0004 yr-1, p < 0.001). The GIMMS FPAR4g, available for half-month intervals at a spatial resolution of 1/12° from 1982 to 2022, promises to be a valuable asset for in-depth analyses of vegetation structures and functions spanning the last 40 years.

Combining Traditional Chinese Herbs and csDMARDs for the Treatment of Rheumatoid Arthritis Involves Tapering and Discontinuing Glucocorticoids: Protocol for a Two-Stage Non-Randomized Controlled Trial.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

Relationship between glutathione S-transferase P1 (GSTP1), X-ray repair cross complementing group 1 (XRCC1) and 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene polymorphisms and response to chemotherapy in advanced gastric cancer.

BACKGROUND: Our study aimed to investigate the relationship between glutathione S-transferase P1 (GSTP1), 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) and X-ray repair cross complementing group 1 (XRCC1) gene polymorphisms and the response to chemotherapy in advanced gastric cancer. PATIENTS AND METHODS: 59 cases of advanced gastric cancer were enrolled. All patients were treated with the DCF regimen comprising docetaxel, cisplatin, and 5-fluorouracil. All patients' genotypes regarding GSTP1, XRCC1, and 5,10-MTHFR were analyzed by polymerase chain reaction/ligase detection reaction (PCR-LDR). RESULTS: There were 15 (25.42%) cases of G/G genotype, 21 (35.59%) of G/A genotype, and 23 (38.98%) of A/A genotype for GSTP1, 16 (27.12%) cases of A/A genotype, 18 (30.51%) of G/A genotype, and 25 (42.37%) of G/G genotype for XRCC1, and 21 (35.59%) cases of C/C genotype, 22 (37.29%) of C/T genotype, and 16 (27.12%) of T/T genotype for 5,10-MTHFR. After 2 cycles of chemotherapy, there were 4 cases of complete remission, 14 of partial remission, 19 of stable disease, and 22 of advanced disease, with a total effective rate of 30.51%. Better survival was shown for GSTP1 G/G genotype, XRCC1 A/A genotype, and 5,10-MTHFR T/T genotype (p < 0.05). CONCLUSION: The gene polymorphisms of GSTP1 G/G, XRCC1 A/A, and 5,10-MTHFR T/T have clinical value for predicting the response to the DCF regimen for advanced gastric cancer.

PD-1 blockade combined with gemcitabine plus nab-paclitaxel is superior to chemotherapy alone in the management of unresectable stage III/IV pancreatic cancer: a retrospective real-world study.

Background: Pancreatic cancer (PC) is widely recognized as one of the most malignant forms of cancer worldwide. Monotherapy with immune checkpoint inhibitors (ICI) has shown limited efficacy in treating this disease. There was controversy surrounding whether combining ICI with chemotherapy provided superior outcomes compared to chemotherapy alone. Methods: In this study, patients diagnosed with unresectable stage III/IV pancreatic cancer (PC) were classified as receiving programmed cell death protein 1 (PD-1) blockade plus gemcitabine and nab-paclitaxel (AG regimen) (PD-1/chemo, n=27, 50.9%) or chemotherapy alone (chemo, n=26, 49.1%) arm. The primary study endpoints included progression-free survival (PFS) and overall survival (OS), with an additional assessment of treatment-related adverse events graded as three or higher. Chi-square (χ2) statistics were employed to analyze the clinical differences between the two groups, while Kaplan-Meier curves were used to assess the difference in PFS and OS. Statistical significance was defined as P-values less than 0.05 (P < 0.05). Results: The median follow-up duration was 22 months (range 1-28 months). In the PD-1/chemo arm, the median PFS was eight months, whereas it was 3.5 months in the chemo arm (HR=0.459, 95% CI: 0.252-0.846, P=0.002). Furthermore, the median OS was 15 months in the PD-1/chemo arm and eight months in the chemo arm (HR=0.345, 95% CI: 0.183-0.653, P<0.001). Within the PD-1/chemo arm, 15 (55.6%) patients experienced grade 3 treatment-related adverse events, compared to 13 (50.0%) patients in the chemo arm. Conclusions: PD-1 blockade combined with nab-paclitaxel plus gemcitabine demonstrated superior efficacy to chemotherapy alone for unresectable stage III/IV PC patients. Future studies were warranted to identify immunosensitive patient subgroups within the PC population, ultimately leading to the development of more efficacious therapeutic strategies.

Coincidence of Systemic Lupus Erythematosus and ANCA-Associated Vasculitis: A Case Report with Perforation of Nasal Septum and Palate.

Background: An overlap of systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibodies- (ANCA-) associated vasculitis (AAV) is extremely uncommon and no clear definition has been proposed. The SLE/AAV overlap syndrome mainly affects kidney, blood count, nervous system and lung. However, few previous cases reported nasal septal and palatal perforation in this disorder. Case Presentation: We presented a case of a 16-year-old female with a 6-month history of SLE, developed perforation of the nasal septum and palate. She was diagnosed with SLE due to facial malar rash, oral ulcer, increased erythrocyte sedimentation rate (ESR), low complement levels, and positive anti-Smith antibody. Approximately 6 months later, she had a perforation of the nasal septum and palate with positive anti-proteinase 3 antibody (anti-PR3-ANCA). A nasal endoscopic biopsy revealed an inflammatory polyp with chronic suppurative inflammation and inflammatory granulomatous hyperplasia. In this case, the clinical, biological, radiological, and histological findings substantiated the diagnosis of AAV. Infections, drug abuse, malignancies, IgG4-related disease (IgG4-RD) and trauma were excluded. So we diagnosed her with SLE/AAV overlap syndrome. Conclusion: When a patient's symptoms cannot be explained by one disease, we need to consider the overlapping of two diseases, especially in patients with autoimmune diseases.