MPT0E028, a novel pan-HDAC inhibitor, prevents pulmonary fibrosis through inhibition of TGF-ß-induced CTGF expression in human lung fibroblasts: Involvement of MKP-1 activation.

Histone deacetylase (HDAC) inhibitors are potential candidates for treating pulmonary fibrosis. MPT0E028, a novel pan-HDAC inhibitor, has been reported to exhibit antitumor activity in several cancer cell lines. In this study, we investigated the mechanism underlying the inhibitory effects of MPT0E028 on the expression of fibrogenic proteins in human lung fibroblasts (WI-38). Our results revealed that MPT0E028 inhibited transforming growth factor-ß (TGF-ß)-, thrombin-, and endothelin 1-induced connective tissue growth factor (CTGF) expression in a concentration-dependent manner. In addition, MPT0E028 suppressed TGF-ß-stimulated expression of fibronectin, collagen I, and α-smooth muscle actin (α-SMA). Furthermore, MPT0E028 inhibited the TGF-ß-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). MPT0E028 reduced the increase in SMAD3 and c-Jun phosphorylation, and SMAD3-and activator protein-1 (AP-1)-luciferase activities under TGF-ß stimulation. Transfection with mitogen-activated protein kinase phosphatase-1 (MKP-1) siRNA reversed the suppressive effects of MPT0E028 on TGF-ß-induced increases in CTGF expression; JNK, p38, and ERK phosphorylation; and SMAD3 and AP-1 activation. Moreover, MPT0E028 increased MKP-1 acetylation and activity in WI-38 cells. Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-ß-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis.

First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma.

PURPOSE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others. CONCLUSION: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. METHODS: ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0-2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). FINDINGS: From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). INTERPRETATION: Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. FUNDING: Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Mitochondria-localizing triphenylphosphine-8-hydroxyquinoline Ru complexes induce ferroptosis and their antitumor evaluation.

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.

A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.

Long-term hematopoietic transfer of the anti-cancer and lifespan-extending capabilities of a genetically engineered blood system by transplantation of bone marrow mononuclear cells.

A causal relationship exists among the aging process, organ decay and disfunction, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/EKLF has been generated that possesses extended lifespan and healthy characteristics, including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti-cancer capability, are likely gender-, age-, and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice, could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at a young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild-type NK cells. Targeted/global gene expression profiling analysis has identified changes in the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/blood system for long-term anti-cancer and, potentially, for anti-aging.

NOT gated T cells that selectively target EGFR and other widely expressed tumor antigens.

Here, we show that a NOT gated cell therapy (Tmod) can exploit antigens such as epidermal growth factor receptor (EGFR) and human leukocyte antigen-E (HLA-E) which are widely expressed on cancer cells. Noncancerous cells-despite high expression of these antigens-are protected from cytotoxicity by the action of an inhibitory receptor ("blocker") via a mechanism that involves blocker modulation of CAR surface expression. The blocker is triggered by the product of a polymorphic HLA allele (e.g., HLA-A∗02) deleted in a significant subset of solid tumors via loss of heterozygosity. Moreover, Tmod constructs that target mouse homologs of EGFR or HLA-E for activation, and a mouse-equivalent of HLA-A∗02 for inhibition, protect mice from toxicity caused by the CAR alone. The blocker also controls graft vs. host response in allogeneic T cells in vitro, consistent with the use of Tmod cells for off-the-shelf therapy without additional gene-editing.

Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund's adjuvant-induced arthritis rats.

BACKGROUND: Adenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA. RESULTS: MA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1ß, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA. CONCLUSION: MA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.

Construction of a nomogram for predicting compensated cirrhosis with Wilson's disease based on non-invasive indicators.

BACKGROUND: Wilson's disease (WD) often leads to liver fibrosis and cirrhosis, and early diagnosis of WD cirrhosis is essential. Currently, there are few non-invasive prediction models for WD cirrhosis. The purpose of this study is to non-invasively predict the occurrence risk of compensated WD cirrhosis based on ultrasound imaging features and clinical characteristics. METHODS: A retrospective analysis of the clinical characteristics and ultrasound examination data of 102 WD patients from November 2018 to November 2020 was conducted. According to the staging system for WD liver involvement, the patients were divided into a cirrhosis group (n = 43) and a non-cirrhosis group (n = 59). Multivariable logistic regression analysis was used to identify independent influencing factors for WD cirrhosis. A nomogram for predicting WD cirrhosis was constructed using R analysis software, and validation of the model's discrimination, calibration, and clinical applicability was completed. Due to the low incidence of WD and the small sample size, bootstrap internal sampling with 500 iterations was adopted for validation to prevent overfitting of the model. RESULTS: Acoustic Radiation Force Impulse (ARFI), portal vein diameter (PVD), and serum albumin (ALB) are independent factors affecting WD cirrhosis. A nomogram for WD cirrhosis was constructed based on these factors. The area under the ROC curve (AUC) of the model's predictive ability is 0.927 (95% CI: 0.88-0.978). As demonstrated by 500 Bootstrap internal sampling validations, the model has high discrimination and calibration. Clinical decision curve analysis shows that the model has high clinical practical value. ROC curve analysis of the model's rationality indicates that the model's AUC is greater than the AUC of using ALB, ARFI, and PVD alone. CONCLUSION: The nomogram model constructed based on ARFI, PVD, and ALB can serve as a non-invasive tool to effectively predict the risk of developing WD cirrhosis.

Effects of movement training based on rhythmic auditory stimulation in cognitive impairment: a meta-analysis of randomized controlled clinical trial.

Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.

The effect of T cell aging on the change of human tissue structure.

The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.

The Relationship between Indoor and Outdoor Fine Particulate Matter in a High-Rise Building in Chicago Monitored by PurpleAir Sensors.

In urban areas like Chicago, daily life extends above ground level due to the prevalence of high-rise buildings where residents and commuters live and work. This study examines the variation in fine particulate matter (PM2.5) concentrations across building stories. PM2.5 levels were measured using PurpleAir sensors, installed between 8 April and 7 May 2023, on floors one, four, six, and nine of an office building in Chicago. Additionally, data were collected from a public outdoor PurpleAir sensor on the fourteenth floor of a condominium located 800 m away. The results show that outdoor PM2.5 concentrations peak at 14 m height, and then decline by 0.11 µg/m3 per meter elevation, especially noticeable from midnight to 8 a.m. under stable atmospheric conditions. Indoor PM2.5 concentrations increase steadily by 0.02 µg/m3 per meter elevation, particularly during peak work hours, likely caused by greater infiltration rates at higher floors. Both outdoor and indoor concentrations peak around noon. We find that indoor and outdoor PM2.5 are positively correlated, with indoor levels consistently remaining lower than outside levels. These findings align with previous research suggesting decreasing outdoor air pollution concentrations with increasing height. The study informs decision-making by community members and policymakers regarding air pollution exposure in urban settings.

Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis: A case report and review of literature.

BACKGROUND: Venous thromboembolism significantly contributes to patient deterioration and mortality. Management of its etiology and anticoagulation treatment is intricate, necessitating a comprehensive consideration of various factors, including the bleeding risk, dosage, specific anticoagulant medications, and duration of therapy. Herein, a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience. CASE SUMMARY: An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d. Considering her medical history and relevant post-admission investigations, it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors, including multiple primary malignant tumors, iliac venous compression syndrome, previous novel coronavirus infection, and inadequate treatment for prior thrombotic events. However, the selection of appropriate anticoagulant medications, determination of optimal drug dosages, and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia, decreased quantitative fibrinogen levels, and renal insufficiency. CONCLUSION: Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis. Individualized anticoagulation therapy is required for complex thrombosis.

Exogenous insulin autoimmune syndrome: A case report and review of literature.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a severe manifestation of spontaneous hypoglycemia. It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies (IAAs), which are induced by endogenous insulin circulating in the bloodstream. It is distinguished by recurring instances of spontaneous hypoglycemia, the presence of IAA within the body, a substantial elevation in serum insulin levels, and an absence of prior exogenous insulin administration. Nevertheless, recent studies show that both conventional insulin and its analogs can induce IAS episodes, giving rise to the notion of non-classical IAS. Therefore, more attention should be paid to these diseases. CASE SUMMARY: In this case report, we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder. Upon symptom onset, the patient exhibited Whipple's triad (including hypoglycemia, blood glucose level less than 2.8 mmol/L during onset, and rapid relief of hypoglycemic symptoms after glucose administration). Concurrently, his serum insulin level was significantly elevated, which contradicted his C-peptide levels. After a comprehensive examination, the patient was diagnosed with exogenous insulin autoimmune syndrome. Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset, it was presumed that non classical IAS was induced by this condition. The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches. CONCLUSION: The occurrence of non-classical IAS is associated with exogenous insulin or its analogs, as well as with sulfhydryl drugs. Symptoms can be effectively alleviated through the discontinuation of relevant medications, administration of hormones or immunosuppressants, plasma exchange, and lifestyle adjustments.

Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS: Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION: The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

Electrolyte Chemistry toward Ultrawide-Temperature (-25 to 75 °C) Sodium-Ion Batteries Achieved by Phosphorus/Silicon-Synergistic Interphase Manipulation.

All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.