A case report of atypical chronic myeloid leukemia with complete hematological and major molecular response to Venetoclax/Azacitidine treatment.

Atypical Chronic Myeloid Leukemia (aCML), a myeloproliferative neoplasm with poor prognosis, was reclassified as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the WHO 2022 classification. Due to the heterogeneity of its clinical features and the lack of unique biomarkers, as well as limited treatment options, aCML currently lacks a standardized treatment protocol. In this case report, we reviewed a young man diagnosed with aCML who achieved complete clinical and hematologic remission subsequent to receiving a therapeutic regimen combining Venetoclax and Azacitidine.

Delineating molecular regulatory network of meat quality of longissimus dorsi indicated by transcriptomic, proteomic, and metabolomics analysis in rabbit.

This study aims to investigate the potential regulatory network responsible for the meat quality using multi-omics to help developing better varieties. Slaughter performance and meat quality of Shuxing No.1 rabbit outperformed IRA rabbit according to the tested rabbit parameters. Differentially expressed genes (DEGs) and differentially abundance proteins (DAPs) were involved in meat quality-related pathways, such as PI3K - Akt and MAPK signaling pathways. Only SMTNL1 and PM20D2 shared between DEGs and DAPs. Olfactory-sensitive undecanal, a differentially abundant metabolite (DAM) in volatilomics (vDAMs), correlated with all of the remaining 11 vDAMs, and most of 12 vDAMs were associated with amino acid metabolism. Integration revealed that 829 DEGs/DAPs were associated with 15 DAMs in four KEGG pathways, such as melatonin (a DAM in widely targeted metabolomics) was significantly positively correlated with ALDH and negatively correlated with RAB3D and CAT in the tryptophan metabolism pathway. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor. SIGNIFICANCE: Shuxing No.1 rabbit is a new breed of meat rabbit in the Chinese market. In meat marketing, meat quality usually determines the purchase intention of consumers. Determining the biological and molecular mechanisms of meat quality in meat rabbit is essential for developing strategies to improve meat quality. According to the tested rabbit parameters, this study ascertained that the slaughter performance and meat quality of Shuxing No.1 rabbit surpasses that of IRA rabbit. The present study profiled the transcriptome, proteome, widely targeted metabolome, and volatilome of longissimus dorsi from Shuxing No.1 rabbit and IRA rabbit. The study found that meat quality and flavor-related tryptophan metabolism pathway is enriched with many DEGs/DAPs (including ALDH, RAB3D, and CAT), as well as a DAM, melatonin. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor.

Anomalous Detachment Behavior and Directional Reconstruction Regulation of Leaching-Type Precatalysts for Industrial Water Electrolyzers.

Current reconstruction chemistry studies are mainly operated at the laboratory scale, where the operating parameters are different from those used in industrial water electrolyzers. This gap leads to unclear reconstruction behaviors under industrial conditions and constrains the application of catalysts. Here, this work presents a new reconstruction mechanism and anomalous detachment phenomena observed in leaching-type oxygen-evolving precatalysts under industrial conditions, different from the reported results obtained under laboratory conditions. The identified detachment issues are closely linked to the production of a potassium salt separate phase, which proves sensitive to the local environment, and its instability easily leads to catalyst stripping from the substrate. By establishing detachment critical point and operating parameter-detachment correlation, a targeted reconstruction strategy is proposed to achieve smooth ligand leaching and effectively solve the detachment issue. Theoretical analyses validate the dual-site regulation in directionally reconstructed catalysts with optimized intermediate adsorption. Under industrial conditions, the coupled electrolyzer delivers an industrial-level current density at low cell voltage with prolonged durability, 1 A cm-2 at 2 V for over 340 h. This work bridges the gap of leaching-type precatalysts between laboratory test conditions and industrial operating conditions.

Establishment and application of recombinase polymerase amplification combined with a lateral flow dipstick for the detection of mcr-1 in uncultured clinical samples.

OBJECTIVES: The rapid dissemination of the mcr-1 gene via plasmid-mediated transfer has raised concerns regarding the efficacy of colistin as a last-resort treatment for multidrug-resistant Gram-negative bacterial infections. Current mcr-1 gene detection methods mainly focus on cultured bacteria, which is a complex and time-consuming process requiring skilled personnel, making it unsuitable for field analysis. METHODS: A rapid detection technique combining recombinase polymerase amplification with a lateral flow dipstick targeting uncultured clinical samples was developed. RESULTS: This new method targeting the mcr-1 gene region (23 232-23 642 bp, no. KP347127.1) achieved a low detection limit of 10 copies/µL. The whole process was carried out with high specificity and was completed within 20 min. The evaluation assay was conducted using 45 human faecal samples; 16 strains yielded a 98% accuracy, closely matching antimicrobial susceptibility outcomes. CONCLUSIONS: The novel method integrates nucleic acid extraction, isothermal amplification, and a test assay, suggesting the potential for timely colistin resistance surveillance in frontline disease control and healthcare settings, supporting future prevention and clinical standardization efforts.

p53 suppresses the inflammatory response following respiratory syncytial virus infection by inhibiting TLR2.

-Respiratory syncytial virus (RSV) is a pivotal virus leading to acute lower respiratory tract infections in children under 5 years old. This study aimed to explore the correlation between p53 and Toll-like receptors (TLRs) post RSV infection. p53 levels exhibited a substantial decrease in nasopharyngeal aspirates (NPAs) from infants with RSV infection compared to control group. Manipulating p53 expression had no significant impact on RSV replication or interferon signaling pathway. Suppression of p53 expression led to heightened inflammation following RSV infection in A549 cells or airways of BALB/c mice. while stabilizing p53 expression using Nutlin-3a mitigated the inflammatory response in A549 cells. Additionally, Inhibiting p53 expression significantly increased Toll-like receptor 2 (TLR2) expression in RSV-infected epithelial cells and BALB/c mice. Furthermore, the TLR2 inhibitor, C29, effectively reduced inflammation mediated by p53 in A549 cells. Collectively, our results indicate that p53 modulates the inflammatory response after RSV infection through TLR2.

Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era

Purpose Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. Methods Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. Results Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91–9.49 months) than group B (2.97 months, 95% CI 2.79–3.15), with a significant difference (P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20–32.21) than in group B (7.37 months, 95% CI 3.85–10.89) (P = 0.016). Conclusion EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations (AU)

Ultrasound for monitoring different stages of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and review of the literature.

RATIONALE: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication in patients with kidney transplantation, which poses challenges in diagnosis and poor prognosis due to its low incidence and nonspecific clinical manifestations. As a routine follow-up examination method for kidney transplant patients, ultrasound (US) plays a significant role in the diagnosis of PTLD. Therefore, it is critical to evaluate the ultrasonic characteristics of PTLD in transplanted kidney patients for early detection and diagnosis. PATIENT CONCERNS: A 59-year-old female patient was unexpectedly found with a mass in the hilum of the transplanted kidney 12th month after transplantation, which gradually grew up in the following 4 months. The latest US examination found hydronephrosis. Contrast-enhanced ultrasound (CEUS) demonstrated a hypo-enhancement pattern in arterial and parenchymal phases and showed a new irregular area lacking perceivable intensification within the mass, which was considered necrosis. Meanwhile, the patient developed an acute increase in serum creatinine from 122 to 195 µmol/L. DIAGNOSIS: A US-guided biopsy was conducted with the final pathological diagnosis of PTLD (polymorphic). INTERVENTIONS: After receiving 3 times of rituximab and symptomatic treatment, blood creatinine returned to normal but the mass was still progressing in the patient. Therefore, the treatment approach was modified to immune-chemotherapy. OUTCOMES: The patient was in a stable condition to date. LESSONS: PTLD is a rare complication in a transplanted kidney. US and CEUS are the preferred imaging methods in renal transplant patients due to their good repeatability and no nephrotoxicity. This case demonstrates that continuous dynamic monitoring by using US and CEUS has significant value in the detection and diagnosis of PTLD in a transplanted kidney, suggesting early clinical intervention to avoid further progression.

Coexistence of a novel SRBD1-ALK, ALK-CACNA1D double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report.

A Chinese male patient with advanced lung adenocarcinoma experienced disease progression one and a half years after receiving first-line immunochemotherapy. The second biopsy was performed and tissue immunohistochemistry revealed Anaplastic lymphoma kinase (ALK) expression in the cytoplasm of tumor cells, so he began to receive Alectinib treatment. Then the next generation sequencing found double fusion variants of S1 RNA binding domain 1 (SRBD1)- ALK and ALK- Calcium voltage-gated channel subunit alpha1 D (CACNA1D). After continuous Alectinib treatment for 7 months, almost complete response (CR) was achieved. The patient is currently taking Alectinib for 13 months, the condition is stable, and is waiting for the next cycle of efficacy evaluation.

Characteristics and prognosis of EGFR mutations in small cell lung cancer patients in the NGS era.

PURPOSE: Targeted therapy has not been effective for small cell lung cancer (SCLC) patients. Although some studies have reported on EGFR mutations in SCLC, a systematic investigation into the clinical, immunohistochemical, and molecular characteristics and prognosis of EGFR-mutated SCLCs is lacking. METHODS: Fifty-seven SCLC patients underwent next-generation sequencing technology, with 11 in having EGFR mutations (group A) and 46 without (group B). Immunohistochemistry markers were assessed, and the clinical features and first-line treatment outcomes of both groups were analyzed. RESULTS: Group A consisted primarily of non-smokers (63.6%), females (54.5%), and peripheral-type tumors (54.5%), while group B mainly comprised heavy smokers (71.7%), males (84.8%), and central-type tumors (67.4%). Both groups showed similar immunohistochemistry results and had RB1 and TP53 mutations. When treated with tyrosine kinase inhibitors (TKIs) plus chemotherapy, group A had a higher treatment response rate with overall response and disease control rates of 80% and 100%, respectively, compared to 57.1% and 100% in group B. Group A also had a significantly longer median progression-free survival (8.20 months, 95% CI 6.91-9.49 months) than group B (2.97 months, 95% CI 2.79-3.15), with a significant difference (P = 0.043). Additionally, the median overall survival was significantly longer in group A (16.70 months, 95% CI 1.20-32.21) than in group B (7.37 months, 95% CI 3.85-10.89) (P = 0.016). CONCLUSION: EGFR-mutated SCLCs occurred more frequently in non-smoking females and were linked to prolonged survival, implying a positive prognostic impact. These SCLCs shared immunohistochemical similarities with conventional SCLCs, and both types had prevalent RB1 and TP53 mutations.

Analysis of Risk Factors of Pelvic Organ Prolapse in Postmenopausal Women and Construction of Prediction Model.

Background: The incidence of Pelvic organ prolapse (POP) was as high as 50% in women, with the main symptoms of vaginal tissue prolapse, accompanied by urination, defecation, and sexual dysfunction, which affected patients' quality of life. POP is more prominent in postmenopausal women due to various factors. By constructing a model, we predict POP and expect to reduce the incidence of POP. Objective: To explore the risk factors for POP in postmenopausal women and develop a predictive model that can identify high-risk individuals early so that targeted preventive measures can be taken to reduce the burden of POP. Methods: Using retrospective studies, 290 menopausal women treated in the Department of Gynecology of the Ninth People's Hospital of Suzhou from January 2019 to December 2022 were selected as the study subjects. Women with menopause were divided into the POP group (62 cases) and a non-POP group (228 cases) according to whether or not POP occurred. Single factor analysis was performed on the two data groups. The risk factors of POP in menopausal women were screened by multivariate logistic regression analysis. Based on the screening results, a graph prediction model expressed as a nomogram is constructed. The model's effectiveness was analyzed by the goodness of fit test and receiver operating characteristic curve (ROC) curve. The decision curve was used to analyze the clinical effectiveness of the model. Results: Multifactor logistic regression analysis showed that Older age (OR = 2.309, P = .007), more childbirth frequency (OR = 3.121, P = .002), low expression of estradiol (E2) (OR = 1.499, P = .023), low expression of serum 25-hydroxyvitamin D3[25-(OH)D3] (OR = 2.073, P = .011), and lower blood calcium (OR = 21.677, P = .014) were all risk factors for POP in menopausal women. Based on the above indicators, a risk prediction model is constructed. The model has been proved to have good recognition ability, areas under curve (AUC) = 0.887 (95%CI: 0.845-0.926), The best cutoff value is 0.37, The sensitivity and specificity were 0.885 and 0.840, respectively; The goodness of fit test showed that the predicted value of the model had no statistical significance with the actual value. The threshold probability is in the range of 1%~99%. The net benefit of menopausal women is higher than the other two extreme curves. It shows that the model is clinically effective. Conclusion: Age, times of delivery, E2, 25-(OH)D3, and blood calcium are related to POP in menopausal women. A nomogram model based on these 5 indicators can effectively assess the risk of POP in postmenopausal women. The clinician can use this column chart to calculate the risk of POP occurrence for each patient and make clinical recommendations accordingly.

Clinical value of ultrasound in adult Wilms' tumor patient with uremia: A case report and literature review.

RATIONALE: Wilms' tumor (WT) is the most common pediatric kidney malignancy and is rarely found in adults. Nonspecific clinical symptoms and imaging features often lead to delayed diagnosis or misdiagnosis of adult WT, resulting in poor clinical outcomes. Ultrasound (US), as an efficient and noninvasive examination method, has been widely used in clinical diagnosis and treatment. Therefore, various US evidence is meaningful to improve understanding of adult WT characteristics in ultrasound. PATIENT CONCERNS: A 45-year-old female patient with uremia (regular hemodialysis for 13 years) with painless gross hematuria was diagnosed with a right kidney tumor penetrating to the lung. Preoperatively, B-mode ultrasonography showed an ill-defined hyperechoic mass in the right kidney, which revealed an unclear border, uneven internal echoes, and calcification. Besides, the internal blood flow signal of the tumor was detected. Contrast-enhanced ultrasound (CEUS) showed an uneven hyper-enhancement in the tumor ("fast in and slow out"). Contrast-enhanced computed tomography of the kidney indicated a similar result as the CEUS. Moreover, the chest CT identified multiple pulmonary metastatic nodules. DIAGNOSES: An ultrasound-guided percutaneous core needle biopsy of the tumor proceeded to make a definite diagnosis of adult WT (epithelial type). INTERVENTIONS: The patient was treated with tislelizumab. OUTCOMES: No progress was found to date. LESSONS: We report the first case in which CEUS was performed in an adult WT patient with uremia and multiple pulmonary metastases. The features obtained by the US can help in the diagnosis of adult WT and direct further diagnostic procedures.

Andrographolide Attenuates RSV-induced Inflammation by Suppressing Apoptosis and Promoting Pyroptosis after Respiratory Syncytial Virus Infection In Vitro.

BACKGROUND: Respiratory syncytial virus (RSV), which is the predominant viral pathogen responsible for causing acute lower respiratory tract infections in children, currently lacks specific therapeutic drugs. Despite andrographolide's demonstrated effectiveness against various viral infections, its effects on RSV infection remain unclear. METHODS: In this study, RSV infection and andrographolide-intervened A549 cell lines were used. The virus load of RSV and the levels of IL-6 and IL-8 in the cell supernatant were quantified. The potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were analyzed using the Gene Expression Omnibus (GEO) database and the PharmMapper Database, and the changes in mRNA expression of these target genes were measured. To further illustrate the effect of andrographolide on the death pattern of RSV-infected airway epithelial cells, Annexin V-FITC/PI apoptosis assays and Western blotting were conducted. RESULTS: Andrographolide decreased the viral load and attenuated IL-6 and IL-8 levels in cell supernatant post-RSV infection. A total of 25 potential targets of andrographolide in the treatment of RSV-infected airway epithelial cells were discovered, and CASP1, CCL5, JAK2, and STAT1 were identified as significant players. Andrographolide noticeably suppressed the increased mRNA expressions of these genes post-RSV infection as well as IL-1ß. The flow cytometry analysis demonstrated that andrographolide alleviated apoptosis in RSV-infected cells. Additionally, RSV infection decreased the protein levels of caspase-1, cleaved caspase-1, cleaved IL-1ß, N-terminal of GSDMD, and Bcl-2. Conversely, andrographolide increased their levels. CONCLUSION: These results suggest that andrographolide may reduce RSV-induced inflammation by suppressing apoptosis and promoting pyroptosis in epithelial cells, leading to effective viral clearance.

Combined small cell lung cancer: current progress and unmet needs.

Combined small cell lung cancer (CSCLC) is a specific subtype of lung cancer characterized by a pathological mixture of small cell lung cancer and any subtype of non-small cell lung cancer components. Currently, our understanding of the clinicopathological features, origin, molecular characterization, treatment, and prognosis of CSCLC remains limited. CSCLCs represent examples of intratumor heterogeneity and pose challenges for accurate diagnosis. Are there any distinct clinicopathologic and molecular differences between pure SCLC and CSCLC? Furthermore, the prognostic outcomes and optimal treatments for CSCLC are urgently needed. This article aims to summarize the current biological features and clinical management of CSCLC, providing a reference for further understanding of this heterogeneous form of small cell lung cancer.

Recurrent pleural effusion as a rare manifestation after prolonged PD1 inhibitor (camrelizumab)-based immunotherapy: A case report.

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

Effects of combining immune checkpoint inhibitors and anti-angiogenic agents on bone metastasis in non-small cell lung cancer patients.

This study aimed to evaluate the efficacy of combining immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in treating lung cancer patients with bone metastases (BMs), as it is unclear whether this combination is effective for this condition. Non-small cell lung cancer patients with BMs receiving ICIs were divided into experimental and control groups based on anti-angiogenic treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, with log-rank test for comparisons. Prognostic factors were determined by univariate and multivariate Cox regression analyses. The study included 95 patients. The experimental group (n = 42) had a higher disease control rate (DCR) (90.5% vs. 68.6%, p = .009), objective response rate (ORR) (35.7% vs. 24.5%, p = .235), and longer median bone PFS (14.3 months vs. 8.3 months, p = .011) for bone metastasis. However, there were no significant differences in overall DCR (92.8% vs. 86.7%, p = .339), ORR (64.3% vs. 62.3%, p = .839), and PFS (12.4 months vs. 11.6 months, p = 0.383) between the 2 groups. The experimental group had a lower incidence of skeleton-related events (SREs) (28.6% vs. 35.8%, p = .425), and SRE patients had shorter PFS (7.7 vs. 14.3 months, p < .001) and OS (12.1 vs. 19.0 months, p = .028). Anti-angiogenic therapy (HR = 0.55, p = .012) and SRE (HR = 2.93, p < .001) were identified as independent prognostic factors for bone metastatic PFS. Adverse events were slightly higher in the experimental group (29.3% vs. 18.9%, p = .238), but not statistically significant. The combination of ICIs and anti-angiogenic agents leads to a significant PFS for BMs and potentially decreases SRE.

A retrospective real-world experience of immunotherapy in patients with extensive stage small-cell lung cancer.

BACKGROUND: The treatment of extensive stage small-cell lung cancer (ES-SCLC) has only made modest progress in the past decade, with two immune checkpoint inhibitors (ICIs), atezolizumab and durvalumab, approved for the treatment of SCLC by January 2022. However, currently, there is limited real-world data on ES-SCLC patients received immunotherapy. METHODS: We retrospectively collected and analyzed the demographic and treatment data of ES-SCLC patients at the First Affiliated Hospital of Guangzhou Medical University from January 2017 to January 2022. Survival and prognosis information was obtained through follow-up. RESULTS: A total of 353 ES-SCLC patients were included, of which 165 received immunotherapy combined with chemotherapy as the first-line (FL) treatment (chemo-immune group), and 188 received chemotherapy (chemotherapy group). The objective response rate (ORR) and disease control rate (DCR) of patients receiving immunotherapy as the FL treatment were better than the chemotherapy group (76.97% vs. 48.40%, p < 0.001, and 83.03% vs. 68.09%, p < 0.001). Moreover, the progression-free survival (PFS) and overall survival (OS) of ES-SCLC patients receiving immunotherapy as the FL treatment were better than the chemotherapy group (6.7 months vs. 5.1 months, p < 0.001, and 12.5 months vs. 11.2 months, p < 0.001). Furthermore, the OS of ES-SCLC patients who received immunotherapy as second-line treatment was better than that in the chemotherapy group (15.9 months vs. 12.9 months, p = 0.036). CONCLUSION: ICIs combined with chemotherapy as the FL treatment could be beneficial to the ORR, DCR, PFS, and OS of ES-SCLC patients. Furthermore, ES-SCLC patients can benefit from ICIs in the second-line treatment, even if they had not received ICIs in the FL treatment.

Defining RSV epidemic season in southwest China and assessing the relationship between birth month and RSV infection: A 10-year retrospective study from June 2009 to May 2019.

Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections (LRTI). However, only limited information is available regarding its seasonality and its relationship with birth month. A retrospective hospital-based study was carried out from June 2009 to May 2019 in Chongqing, southwest of China. LRTI cases under 5 years were enrolled in this study and PCR was used to detect 8 respiratory viruses. RSV seasonality was determined using "average annual percentage" (AAP) and "percent positivity" method. A total of 6991 cases were enrolled in this study, with an RSV positivity of 34.5%. From June 2009 to May 2019, we analyzed RSV epidemic season during 10 RSV epidemic years in Chongqing using two methods. The result of AAP method was similar to that of percent positivity method with a 30% threshold, which showed an epidemic season of roughly October to March in the subsequent year, with a small peak in June. On average, the RSV epidemic season in RSV-A dominant years typically started earlier (week 42 for RSV-A vs. week 46 for RSV-B), ended earlier (week 12 for RSV-A vs. week 14 for RSV-B), lasted longer (24 weeks for RSV-A vs. 22 weeks for RSV-B), and reached its peak earlier (week 2 for RSV-A vs. week 3 for RSV-B) than in RSV-B dominant years. The proportion of severe LRTI was higher in cases of single infection with RSV-A compared to those of single infection with RSV-B (26.3% vs. 22.3%, p = 0.024). Among infants under 1 year, those born in May and August through December were more likely to be infected with RSV. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection. In Chongqing, the RSV epidemic was seasonal and usually lasted from October to March of next year with a small peak in summer. Infants born 1-2 months before the epidemic season were relatively more susceptible to RSV infection and this population should be targeted while developing RSV immunization strategies.

Stratification of non-small cell lung adenocarcinoma patients with EGFR actionable mutations based on drug-resistant stem cell genes.

EGFR-TKIs were used in NSCLC patients with actionable EGFR mutations and prolong prognosis. However, most patients treated with EGFR-TKIs developed resistance within around one year. This suggests that residual EGFR-TKIs resistant cells may eventually lead to relapse. Predicting resistance risk in patients will facilitate individualized management. Herein, we built an EGFR-TKIs resistance prediction (R-index) model and validate in cell line, mice, and cohort. We found significantly higher R-index value in resistant cell lines, mice models and relapsed patients. Patients with an elevated R-index had significantly shorter relapse time. We also found that the glycolysis pathway and the KRAS upregulation pathway were related to EGFR-TKIs resistance. MDSC is a significant immunosuppression factor in the resistant microenvironment. Our model provides an executable method for assessing patient resistance status based on transcriptional reprogramming and may contribute to the clinical translation of patient individual management and the study of unclear resistance mechanisms.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

A case report and literature review on respiratory failure with immune checkpoint inhibitors: a life-threatening adverse event.

Neuromuscular associated respiratory failure is a rare toxicity of immunotherapy for malignant tumors. In most cases, it may overlap with the symptoms of the primary disease or myocarditis, myositis and myasthenia gravis, resulting in difficult etiological diagnosis. Early detection and optimal treatment are still topics that need attention. Here, a case of 51-year-old male lung cancer patient with sintilimab-associated myasthenia gravis, myositis, and myocarditis overlap syndrome involving the diaphragm who developed severe type II respiratory failure was reported. After high-dose methylprednisolone, immunoglobulin and pyridostigmine intravenous injection with non-invasive positive pressure ventilation, the patient's symptoms improved significantly and was discharged. One year later, the patient received immunotherapy again due to tumor progression. After 53 days, he developed dyspnea again. Chest X-ray demonstrated marked elevation of the diaphragm, and the electromyogram demonstrated dysfunction of diaphragm. With rapid diagnosis and timely treatment, the patient was finally discharged safely. A comprehensive search of PubMed, EMBASE was performed to identify all previously reported cases of immune checkpoint inhibitors-associated respiratory failure. The potential mechanisms of respiratory failure caused by ICI-associated diaphragmatic dysfunction may be related to T cell-mediated immune disturbances and we proposed possible diagnostic processes. For patients with unexplained respiratory failure who are receiving immunotherapy, standardized diagnostic strategies should be implemented immediately on admission before deciding whether to conduct a more invasive diagnostic procedure or empirical treatment.