Transforming healthcare performance monitoring - A cutting-edge approach with generalized additive profiles: GAMs for healthcare quality monitoring.

Recent findings indicate a growing trend in data analysis within healthcare using statistical process control. However, the diversity of variables involved necessitates the expansion of new process control methodologies. This study examined control chart applications in cardiology by using generalized additive models (GAMs) to construct profiles while involving multiple healthcare variables (08). Two distinct statistics: deviation (D), and Hotelling (T2) were employed for constructing control charts: a commonly used single-variable statistic for nonparametric profiles and an innovative multivariate statistic that assesses the contribution of each element to process changes. These statistics were tested for monitoring ischemic and hemorrhagic strokes in 1-year acute stroke (369) patients at the Faisalabad Institute of Cardiology. Demographic parameters (age, gender), vascular risk factors (diabetes, family history, sleep), socioeconomic variables (smoking, location), and blood pressure are included in the model. The research includes the computation of zero-state average run length (ARL) for assessing the performance of control charts. The characteristics of the proposed profile were analyzed, such as the T2 control chart, performing better than the D chart for medium-to-large shifts (δ ≥ 0.50). On the other hand, for small δ = 0.25, the D control chart produces smaller ARL values but more significant standard deviations. While both statistics contribute to profile monitoring, T2 is more effective at identifying and tracing medium and large shifts. In conclusion, such handy tools may aid healthcare performance monitoring, especially for complicated predictor-response relationships. Monitored profiles demonstrated that GAMs are useful for healthcare analysis and process monitoring.

Mechanochemical Upcycling of Waste Polypropylene into Warm-Mix Modifier for Asphalt Pavement Incorporating Recycled Concrete Aggregates.

To solve the problems on resource utilization and environmental pollution of waste concrete and waste polypropylene (PP) plastics, the recycling of them into asphalt pavement is a feasible approach. Considering the high melting temperature of waste PP, this study adopted a thermal-and-mechanochemical method to convert waste PP into high-performance warm-mix asphalt modifiers (PPMs) through the hybrid use of dicumyl peroxide (DCP), maleic anhydride (MAH), and epoxidized soybean oil (ESO) for preparing an asphalt mixture (RCAAM) containing recycled concrete aggregate (RCA). For the prepared RCAAM containing PPMs, the mixing temperature was about 30 °C lower than that of the hot-mix RCAAM containing untreated PP. Further, the high-temperature property, low-temperature crack resistance, moisture-induced damage resistance, and fatigue resistance of the RCAAM were characterized. The results indicated that the maximum flexural strain of the RCAAM increased by 7.8~21.4% after using PPMs, while the sectional fractures of the asphalt binder were reduced after damaging at low temperature. The use of ESO in PPMs can promote the cohesion enhancement of the asphalt binder and also improve the high-temperature deformation resistance and fatigue performance of the RCAAM. Notably, the warm-mix epoxidized PPMA mixture worked better close to the hot-mix untreated PPMA mixture, even after the mixing temperature was reduced by 30 °C.

Prognostic Value of Easy Albumin-Bilirubin Score for Radical Surgery in Patients With Gallbladder Carcinoma.

BACKGROUND: To investigate the clinical significance of the easy albumin-bilirubin (EZ-ALBI) score as a prognostic indicator in postoperative patients with gallbladder carcinoma (GBC). METHODS: The comprehensive clinical and pathological records of 140 patients with GBC who underwent radical resection between January 2015 and December 2020 were retrospectively examined. Based on the EZ-ALBI score, the 140 GBC patients were categorized into two groups: a low EZ-ALBI score group (score ≤ -34.4) consisting of 108 patients and a high EZ-ALBI score group (score > -34.4) consisting of 32 patients. The association between the EZ-ALBI score and clinicopathological factors was assessed. Survival analysis was performed using the Kaplan-Meier method, and the Cox proportional hazard model was utilized to evaluate the impact of clinicopathological factors on prognosis. RESULTS: Significant differences were observed between the low EZ-ALBI score group and the high EZ-ALBI score group in terms of serum total bilirubin, serum albumin, CA19-9 levels, liver metastasis, and tumor TNM stage. The 5-year survival rate was significantly lower in the high EZ-ALBI score group compared to the low EZ-ALBI score group. Univariate analysis indicated that serum total bilirubin, lymph node metastasis, TNM stage, and EZ-ALBI score were closely related to overall survival (OS). Multivariate analysis identified TNM stage and EZ-ALBI score as independent prognostic factors for OS. CONCLUSIONS: The EZ-ALBI score is a significant independent prognostic factor for overall survival in GBC patient's post-radical resection, highlighting its potential utility in clinical prognosis and patient management.

SOX4 inhibits ferroptosis and promotes proliferation of endometrial cancer cells via the p53/SLC7A11 signaling.

AIM: Sex-determining region Y-related high-mobility group box 4 (SOX4) has been reported to play a carcinogenic role in endometrial cancer (EC). However, the biological function and regulatory mechanisms of SOX4 in ferroptosis during the progression of EC are still unknown. METHODS: The mRNA and protein levels were scrutinized by quantitative reverse-transcription polymerase chain reaction and western blot, respectively. The cell viability and proliferative capability were determined by cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Transcriptional regulation of gene expression was investigated by dual-luciferase reporter assay and chromatin immunoprecipitation. Ferroptosis was evaluated by detection of reactive oxygen species, malondialdehyde, Fe2+, and ferroptosis-related proteins. The mice test was implemented to confirm the influence of SOX4 on EC tumor growth and ferroptosis in vivo. RESULTS: We here discovered the elevation of SOX4 in EC tissues and cells. Functionally, SOX4 knockdown hampered proliferation and promoted ferroptosis of EC cells. Mechanistically, SOX4 bound to p53 promoter and inhibited its transcriptional activity in EC cells. In addition, p53 transcriptionally suppressed SLC7A11 expression in EC cells. Downregulation of p53 reverses the effect of SOX4 knockdown on proliferation and ferroptosis of EC cells. Finally, in vivo experiments demonstrated that SOX4 depletion hindered tumor growth and triggered ferroptosis in EC. CONCLUSIONS: These findings collectively suggested that SOX4 inhibited ferroptosis and promoted proliferation of EC cells via the p53/SLC7A11 signaling. Our research unveiled a novel regulatory mechanism of ferroptosis in EC, offering promising perspectives for the development of EC therapies.

The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis.

Background: With the increasing use of hormone replacement therapy (HRT), there is a need to understand its impact on the occurrence of female malignant tumors. This systematic review and meta-analysis aimed to assess the risk of ovarian cancer associated with HRT and its related risk factors. Methods: PUBMED, OVID, Embase, Cochrane, and Web of Science were searched from 1980 to April 2022 to identify studies on the risk of ovarian cancer and hormone replacement therapy. The random-effects model was used to estimate the pooled risk of HRT in ovarian cancer, both in cohort studies and case-control studies. Additionally, the analysis examined the outcomes associated with different types of estrogen plus progesterone regimens. Meta-regression and sensitive analysis were performed to evaluate the heterogeneity. Results: 21 cohort studies (involving 15,313 cases and 4,564,785 participants) and 30 case-control studies (including 18,738 cases and 57,747 controls) were analyzed. The pooled risks of ovarian cancer for HRT users were 1.20 (95% confidence interval [CI] 1.01-1.44) from cohort studies and 1.13 (95%CI 1.04-1.22) from case-control studies. However, after restricting the study period to recent decades, the significant results indicating a higher risk disappeared in cohort studies conducted after 2010 and in case-control studies conducted after 2006. Furthermore, the continuous use of estrogen-progesterone replacement therapy (EPRT) was associated with a risk comparable to that of sequential use. Subgroup analysis showed that both estrogen replacement treatment (ERT) and EPRT had minor risks; The risk further increased with prolonged exposure time, particularly for durations exceeding 10 years. Additionally, serous ovarian cancer appeared to be more susceptible than other pathological types. Conclusion: The risk of ovarian cancer associated with HRT has been decreasing over time. However, ERT may increase this risk, particularly when used for an extended period. It is recommended that long-time users consider continuous EPRT as a safer alternative. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier CRD42022321279.

H2O2 oxidation - CaO precipitation pretreatment combining forward osmosis for electroless nickel spent tank liquid (ENSTL) reduction.

The electroless nickel spent tank liquid (ENSTL), as a typical hazardous waste, contains a variety of refractory organic substances as well as heavy metals and inorganic salts. Generally, ENSTL is delegated for disposing by qualified hazardous waste disposal departments in China. However, the temporary storage, transportation, and higher entrusted disposal expenses increase the burden on enterprises producing the hazardous ENSTL. This paper explored an oxidation/precipitation pretreatment and forward osmosis (FO) combined process for ENSTL reduction. 400 mmol/L Hydrogen peroxide and 5.0 wt% calcium oxide were selected as the optimal pretreatment in order to minimize the osmotic pressure of ENSTL, by which the conductivity was significantly reduced from 50.8 mS/cm to 26.8 mS/cm. As a result, the concentrating factor (N) could be dramatically increased from 2.45 by the direct FO to 8.71 by the combined system. Accordingly, the average water flux during the 24 h concentrating cycle increased from 2.47 L/(m2·h) to 4.56 L/(m2·h). TOC rejection rate decreased from 90.23% to 84.39% due to the transformation of organic matter forms by the chemical oxidation during the pretreatment. Meanwhile, TP, Ni and NH4+ rejection rates decreased to a certain extent, which may related to the mitigation of membrane fouling by the pretreatment.

[Cluster nursing care based on 10S continuous quality improvement reduces incidence of postoperative delirium in BPH patients].

OBJECTIVE: To study the effect of cluster nursing care based on 10S continuous quality improvement (CQI) on the incidence of postoperative delirium in patients with BPH. METHODS: This study included 96 BPH patients undergoing transurethral resection of the prostate (TURP) in our department from August 2021 to February 2023. We randomly divided the patients into two groups of equal number to receive routine postoperative nursing care (the control group) and postoperative cluster nursing care based on the 10S DQI mode (the observation group), respectively. We recorded and compared the delirium scores of the patients at 2, 6, 12 and 24 hours after operation, their status of recovery, scores on Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and quality of life (QOL), and incidence of complications between the two groups. RESULTS: Compared with the controls, the patients in the observation group showed significantly lower delirium scores at 2 h (12.72±3.54 vs 10.65±2.87, P<0.05), 6 h (20.17±4.92 vs 14.19±4.64, P<0.01), 12 h (16.82±4.24 vs 10.69±3.18, P<0.01) and 24 h (13.61±2.86 vs 9.13±2.12, P<0.01) after operation, and shorter time to ambulation (ï¼»3.65±1.41ï¼½ vs ï¼»2.84±0.83ï¼½ d, P<0.01) and time of postoperative catheterization (ï¼»6.28±1.65ï¼½ vs ï¼»4.28±1.14ï¼½ d, P<0.01), bladder irrigation (ï¼»3.41±1.08ï¼½ vs ï¼»2.25±0.71ï¼½ d, P<0.01) and hospitalization (ï¼»10.33±2.41ï¼½ vs ï¼»7.82±2.06ï¼½ d, P<0.01). No statistically significant differences were observed between the two groups in either the SAS and SDS scores (P >0.05) or the QOL scores before operation (P >0.05), but the former two were dramatically decreased (P<0.01) while the latter one increased in the observation group postoperatively (P<0.01). Postoperative complications included delirium, bladder spasm, urethral pain, and secondary bleeding, with a significantly lower total incidence rate in the observation than in the control group (12.50% vs 52.08%, P<0.01). CONCLUSION: Cluster nursing care based on 10S CQI can promote the postoperative recovery of BPH patients, improve their psychological status and quality of life, and reduce the incidence of delirium and complications.

Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes.

Endoplasmic reticulum stress may affect the occurrence and development of cancer. However, its effect on the prognosis of colon cancer (CC) patients is not clear yet. Herein, based on TCGA database, we screened 15 endoplasmic reticulum stress responsive genes (ERSRGs) associated with the prognosis of CC patients by Cox regression. By LASSO and multivariate Cox regression analyses, a prognostic risk assessment model involving 12 genes (DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, GRIN2B, LRRC59, and RORC) was built. The survival curves indicated that patients in the low-risk group had good prognosis. ROC curves demonstrated a good performance of this 12-gene prognostic model, and the Riskscore could be considered as an independent prognostic factor. Patients in low-risk group benefit more from immune checkpoint inhibitor and immune checkpoint blockade (ICB) treatment. Besides, the enrichment analysis suggested a remarkable difference in Ca2+ signaling in both groups. Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. To sum up, our research constructed an ERSRGs-characteristic prognostic model. The model is a promising biomarker for prediction of clinical outcomes and immune therapy response of CC patients. SIGNIFICANCE: Based on the transcriptomic data of colon cancer in the TCGA database, this study screens 12 endoplasmic reticulum stress-related genes (ERSRGs), including DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, asphD1, NTRK2. GRIN2B, LRRC59, and RORC, and a prognostic model was constructed. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.

Carbon monoxide-releasing molecule-3 exerts neuroprotection effects after cardiac arrest in mice: A randomized controlled study.

Background: Post-cardiac arrest brain injury (PCABI) is the leading cause of death in survivors of cardiac arrest (CA). Carbon monoxide-releasing molecule (CORM-3) is a water-soluble exogenous carbon monoxide that has been shown to have neuroprotection benefits in several neurological disease models. However, the effects of CORM-3 on PCABI is still unclear. Methods: A mice model combined asystole with hemorrhage was used. Mice were anesthetized and randomized into 4 groups (n = 12/group) and underwent either 9.5 min CA followed by cardiopulmonary resuscitation (CPR) or sham surgery. CORM-3 (30 mg/kg) or vehicle (normal saline) were administered at 1 h after return of spontaneous circulation or sham surgery. Survival, neurologic deficits, alterations in the permeability of the brain-blood barrier and cerebral blood flow, changes of oxidative stress level, level of neuroinflammation and neuronal degeneration, and the activation of Nrf2/HO-1 signaling pathway were measured. Results: In CORM-3 treated mice that underwent CA/CPR, significantly improved survival (75.00% vs. 58.33%, P = 0.0146 (24 h) and 66.67% vs. 16.67%, P < 0.0001 (72 h)) and neurological function were observed at 24 h and 72 h after ROSC (P < 0.05 for each). Additionally, increased cerebral blood flow, expression of tight junctions, and reduced reactive oxygen species generation at 24 h after ROSC were observed (P < 0.05 for each). CORM-3 treated mice had less neuron death and alleviated neuroinflammation at 72 h after ROSC (P < 0.05 for each). Notably, the Nrf2/HO-1 signaling pathway was significantly activated in mice subjected to CA/CPR with CORM-3 treatment. Conclusions: CORM-3 could improve survival and exert neuroprotection after CA/CPR in mice. CORM-3 may be a novel and promising pharmacological therapy for PCABI.

[Diagnosis and treatment of small-cell carcinoma of the prostate: A report of 2 cases].

OBJECTIVE: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP). METHODS: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature. RESULTS: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesⅡ－Ⅲ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day. CONCLUSION: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.

[Correlation between autophagy-associated miRNAs and prostate cancer: An update].

Prostate cancer (PCa) is one of the common tumors in the genitourinary system, with an increasing morbidity and mortality in China. Recent studies show that autophagy plays an important pathophysiological role in many diseases, including cancers. Besides, some miRNAs are also key regulatory factors for autophagy in PCa cells, and play an important role in the development, progression, diagnosis and treatment of PCa. In-depth studies of miRNAs may contribute to the discovery of some valuable diagnostic methods and novel treatment strategies. This article reviews the progress in researches on the role of autophagy-related miRNAs in PCa, aiming to provide some reference for the diagnosis and treatment of the malignancy.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis.

BACKGROUND: Despite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening. METHOD: A comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092. RESULTS: From an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity. CONCLUSIONS: Among the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Prognosis of unresected versus resected early-stage pulmonary carcinoid tumors ≤3 cm in size: A population-based study.

PURPOSE: The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis. METHODS: Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups. RESULTS: In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter. CONCLUSION: Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction.

BACKGROUND: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. METHODS: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. RESULT: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. CONCLUSION: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.

Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy: A case report.

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare type of non-small-cell lung cancer. Stomach lymphoepithelioma-like carcinoma (LELC) metastasis secondary to PLELC has not been reported recently. CASE SUMMARY: A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC. Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region. Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus. Immunohistochemistry (IHC) of the biopsy suggested metastatic stomach LELC. Proximal gastrectomy showed that this 6.5 cm × 5.0 cm mass was located in the stomach fundus near the cardia. Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration. IHC demonstrated that the tumor was positive for CK (AE1/AE3), p63, p40, p53, Ki-67 (70%), and EGFR (3+) and negative for CK7, CK20, Her2, and CD10. In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA. Tumor programmed cell death ligand 1 (PD-L1) expression score was 98%, and the combined positive score was 100, with no evidence of microsatellite instability. Thus, the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC. After discharge, this patient underwent PD-1 inhibitor treatment (toripalimab, 240 mg) every 3 wk for ten cycles, and she has had no tumor recurrence. CONCLUSION: For gastric LELC metastasis, PD-1 inhibitor therapy could become a new therapeutic approach, though there is still no evidence from large data sets to support this.

Cancer progression and tumor hypercoagulability: a platelet perspective.

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.

The efficacy and safety of local 5-aminolevulinic acid-based photodynamic therapy in the treatment of cervical high-grade squamous intraepithelial lesion: a single center retrospective observational study.

Background: Typical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL. Methods: A total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7-14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation. Results: Three months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms. Conclusion: ALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.

The interaction of Pu.1 and cMyb in zebrafish neutrophil development.

Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited. PU.1 and cMYB participate in multiple stages of neutrophil development, and their abnormalities are often associated with hematologic disorders. However, the regulatory relationship between these factors in vivo and their mode of interaction remain unclear. In this study, zebrafish models with cMyb overexpression (cmybhyper) and Pu.1 deficiency (pu.1G242D/G242D) were utilized to systematically investigate the interaction between Pu.1 and cMyb during granulopoiesis through whole-mount in situ hybridization, qRT-PCR, fluorescence reporting systems, and rescue experiments. The results showed a significant increase in cmyb expression in neutrophils of the pu.1G242D/G242D mutant, while there was no apparent change in pu.1 expression in cmybhyper. Further experiments involving injection of morpholino (MO) to decrease cmyb expression in pu.1G242D/G242D mutants, followed by SB and BrdU staining to assess neutrophil quantity and proliferation, revealed that reducing cmyb expression could rescue the abnormal proliferation phenotype of neutrophils in the pu.1G242D/G242D mutant. These findings suggest that Pu.1 negatively regulates the expression of cMyb during neutrophil development. Finally, through the construction of multi-site mutation plasmids and a fluorescent reporter system, confirmed that Pu.1 directly binds to the +72 bp site in the cmyb promoter, exerting negative regulation on its expression. In conclusion, this study delineates that Pu.1 participates in neutrophil development by regulating cmyb expression. This provides new insights into the regulatory relationship between these two factors and their roles in diseases.

Intravascular Leiomyoma Considered Preoperatively as Uterine Sarcoma: A Rare Case.

Intravascular leiomyoma (IVL) is usually defined as a histologically benign leiomyoma that originates in a uterine fibroid or the intrauterine vein wall and grows and expands intravenously. We report a case in which pelvic IVL was detected early and discuss the early diagnosis of and best treatment for this tumor.