The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

BACKGROUND: Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. AIM: This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. METHODS: This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). RESULTS: The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1 m) while the mOS was 12.3 months (95% CI: 7.6-18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. CONCLUSIONS: The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. CLINICALTRIALS: GOV: NCT05574998.

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS: We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS: Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION: Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.

Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC.

The epidermal growth factor receptor (EGFR) Thr790 Met (T790M) mutation is responsible for approximately half of the acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. Identifying patients at diagnosis who are likely to develop this mutation after first- or second-generation EGFR-TKI treatment is crucial for better treatment outcomes. This study aims to develop and validate a radiomics-based machine learning (ML) approach to predict the T790M mutation in NSCLC patients at diagnosis. We collected retrospective data from 210 positive EGFR mutation NSCLC patients, extracting 1316 radiomics features from CT images. Using the LASSO algorithm, we selected 10 radiomics features and 2 clinical features most relevant to the mutations. We built models with 7 ML approaches and assessed their performance through the receiver operating characteristic (ROC) curve. The radiomics model and combined model, which integrated radiomics features and relevant clinical factors, achieved an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.79-0.81) and 0.86 (0.87-0.88), respectively, in predicting the T790M mutation. Our study presents a convenient and noninvasive radiomics-based ML model for predicting this mutation at the time of diagnosis, aiding in targeted treatment planning for NSCLC patients with EGFR mutations.

Validation of the ABCD3-I score to predict stroke risk after transient ischemic attack.

BACKGROUND AND PURPOSE: The Age, Blood Pressure, Clinical Features, Duration, and Diabetes plus Dual TIA (ABCD(3)-I) score is recommended to predict the risk of early stroke after transient ischemic attack. The aim of this study was to validate the predictive value of the ABCD(3)-I score and compare the accuracy of the Age, Blood Pressure, Clinical Features, Duration, and Diabetes (ABCD(2)) and ABCD(3)-I scores in a Chinese population. METHODS: Data were prospectively collected from patients who had transient ischemic attack, as defined by the World Health Organization time-based criteria. ABCD(2) and ABCD(3)-I scores were available within 7 days of the index transient ischemic attack. The predictive outcome was stroke occurrence at 90 days. The receiver-operating characteristic curves were plotted, and the C statistics were calculated as a measure of predictive ability. The comparison of the area under the receiver-operating characteristic curve (area under the curve) was performed by Z test. RESULTS: Among 239 eligible patients, the mean age was 57.4±13.32 years, and 40.2% of the patients were women. The incidence of stroke at 90 days was 12.1%, which ranged from 0% in patients with lower ABCD(3)-I scores (0-3) to 40.91% in those with higher scores of 8 to 13 (P for trend <0.0001). Moreover, the C statistic of ABCD(3)-I scores (0.825; 95% confidence interval, 0.752-0.898) was statistically higher than that of ABCD(2) scores (0.694; 95% confidence interval, 0.601-0.786; P<0.001). CONCLUSIONS: The ABCD(3)-I score had a higher predictive value than the ABCD(2) score for assessing the risk of early stroke after transient ischemic attack in a Chinese population.

[Correlation of H-type hypertension and prognosis of ischemic stroke].

OBJECTIVE: To examine the correlation between hypertension with hyperhomocysteinemia and prognosis of ischemic stroke. METHODS: A total of 634 patients with acute ischemic stroke confirmed by computed tomography or magnetic resonance imaging were recruited at Department of Neurology, First Affiliated Hospital, Zhengzhou University from January 1, 2007 to May 30, 2010. Their NIHSS (National Institute of Health Stroke Scale) scores were evaluated on admission. And their baseline profiles and probable prognostic factors were recorded. Recovery was assessed by modified Rankin score (MRS) during a 6-month follow-up. Multivariate Logistic regression was performed for statistical analysis. RESULTS: Among them, 32 became lost to follow-up. There were 197 females (32.7%) and 405 males (67.3%) with an average age of (59 ± 13) years (range: 19 - 92). The average level of homocysteine was (19 ± 11) µmol/L. There were 343 (57%) patients with hypertension and MRS ≥ 3 was in 145 (31%) patients. Logistic regression analysis showed that significant correlations existed between H-type hypertension and 6-month MRS (P = 0.012, OR = 2.566, 95%CI: 1.299 - 5.357) when homocysteine ≥ 15 µmol/L was defined for hyperhomocysteinemia. And there was a total sum of interaction between hypertension and hyperhomocysteinemia. The parameters of relative excess risk of interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S) were 0.683, 26.61% and 1.59 respectively. Other parameters with significant prognostic correlations included age, history of stroke, NIHSS score on admission and diastolic blood pressure on admission. CONCLUSION: At the homocysteine level of ≥ 15 µmol/L, H-type hypertension and 6-month MRS have significant correlations. And H-type hypertension is a risk factor for the prognosis of ischemic stroke. When hypertension and hyperhomocysteinemia coexist, there is a total sum of interaction.

Pleural involvements in pulmonary sarcoidosis: A case report and review of the literature.

As a chronic and multisystemic granulomatosis of unknown origin, sarcoidosis can affect multiple organs throughout the body with variable progression and prognosis. Sarcoidosis may present with a battery of symptoms and signs, such as dyspnea, non-productive cough, uveitis, and erythema nodosum. Although the lungs and mediastinal lymph nodes are almost affected in sarcoidosis, involvements of the pleurae remain uncommon. Herein, we report a case of sarcoidosis with both pleural effusions and pleural nodules as confirmed by thoracoscopic pleural biopsy.

Hematological malignancies in systemic lupus erythematosus: clinical characteristics, risk factors, and prognosis-a case-control study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic and complex multi-system autoimmune disorder. Higher risks of hematological malignancies (HM) were observed in SLE patients, which was associated with higher mortality. The mechanism and risk factors of HM oncogenesis in SLE patients are still under investigation. The aim of this study was to explore clinical characteristics, risk factors, and prognosis of SLE patients with or without HM in the Chinese population. METHODS: A retrospective, case-controlled study was conducted in 72 SLE patients between January 2013 and December 2020. Clinical and laboratory data were collected and compared between the two groups of patients with HM and those without HM. Logistic regression analysis was performed to determine risk factors of HM oncogenesis. The survival rate was estimated by Kaplan-Meier methods and Cox proportional hazards regression analysis. RESULTS: Among 72 SLE patients in this study, fifteen complicated with HM and 57 without HM were identified. The incidence rate of HM was approximately 0.24% with elevated standardized incidence ratios of lymphoma and leukemia (27.559 and 12.708, respectively). Patients with HM were older when diagnosed with SLE, with a higher frequency of infection and splenomegaly, lower levels of hemoglobin and high-density lipoprotein compared with those without HM. Fewer patients with HM expressed positive anti-dsDNA antibody (26.7% vs 66.7%, P = 0.005) or received hydroxychloroquine treatment (40.0% vs 86.0%, P = 0.001). Older age at SLE diagnosis (OR=1.122, 95% CI: 1.037-1.214) was regarded as an independent risk factor of HM oncogenesis. Female (RR= 0.219, 95% CI: 0.070-0.681) and hydroxychloroquine (RR= 0.281, 95% CI: 0.094-0.845) were protective factors of mortality in SLE patients. CONCLUSIONS: SLE patients with an older age are at an increased risk of HM carcinogenesis. The prognosis of male patients with SLE tends to be poorer whether complicated with HM. The association of antinuclear antibody spectrum, medication, and HM oncogenesis in SLE needs further investigation.

Interleukin­27 ameliorates allergic asthma by alleviating the lung Th2 inflammatory environment.

Interleukin (IL)­27 can inhibit the differentiation of Th2 cells and plays a role in the development of asthma. However, whether the therapeutic administration of IL­27 in a mouse model of asthma can inhibit allergic responses remains a matter of debate. Additionally, the mechanisms through which IL­27 ameliorates inflammatory responses in asthma are not yet fully understood. Thus, the aim of the present study was to examine the effects of IL­27 on asthma using a mouse model and to elucidate the underlying mechanisms. For this purpose, mice received an intranasal administration of IL­27 and the total and differential cell counts, levels of cytokines and type 1 regulatory T (Tr1) cells in the lungs were detected. The protein and mRNA levels of signal transducer and activator of transcription (STAT)1 and STAT3 were analyzed and airway remodeling was assessed. The results indicated that IL­27 did not ameliorate airway inflammation, airway hyperresponsiveness, and airway remolding when administrated therapeutically. Preventatively, the administration of IL­27 decreased the concentrations of Th2 cytokines and increased the number of Tr1 cells. The protein and mRNA levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrate that the prophylactic administration of IL­27 ameliorates asthma by alleviating the lung Th2 inflammatory environment through the restoration of both the STAT1 and STAT3 pathways. IL­27 may thus prove to be useful as a novel agent for the prevention of asthma.

Machine Learning-Based Radiomics for Prediction of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.

Identifying an epidermal growth factor receptor (EGFR) mutation is important because EGFR tyrosine kinase inhibitors are the first-line treatment of choice for patients with EGFR mutation-positive lung adenocarcinomas (LUAC). This study is aimed at developing and validating a radiomics-based machine learning (ML) approach to identify EGFR mutations in patients with LUAC. We retrospectively collected data from 201 patients with positive EGFR mutation LUAC (140 in the training cohort and 61 in the validation cohort). We extracted 1316 radiomics features from preprocessed CT images and selected 14 radiomics features and 1 clinical feature which were most relevant to mutations through filter method. Subsequently, we built models using 7 ML approaches and established the receiver operating characteristic (ROC) curve to assess the discriminating performance of these models. In terms of predicting EGFR mutation, the model derived from radiomics features and combined models (radiomics features and relevant clinical factors) had an AUC of 0.79 (95% confidence interval (CI): 0.77-0.82), 0.86 (0.87-0.88), respectively. Our study offers a radiomics-based ML model using filter methods to detect the EGFR mutation in patients with LUAC. This convenient and low-cost method may be of help to noninvasively identify patients before obtaining tumor sample for molecule testing.

A highly elastic, Room-temperature repairable and recyclable conductive hydrogel for stretchable electronics.

Conductive hydrogels present great potential in bioelectronics, ionotronic devices, and electronic skin. However, the creeping and plastic deformation of hydrogel often lead to poor stability and low reliability in applications. Here, we report a highly elastic conductive hydrogel based on crosslinked carbon nanotubes (CNT) and poly(vinyl alcohol) (PVA). With the formation of double crosslinking interactions, i.e., strong interaction from covalent acetal bonds and weak interaction from hydrogen bonds, CNT-PVA networks exhibit good stretchability (fracture stain up to 500%), rapid recovery, zero-residual deformation, and excellent mechanical stability. As such, the electromechanical response of this dual-crosslinked conductive hydrogel is stable and repeatable for a wide range of loading rates. Benefiting from the abundant hydroxyl groups and reversible acetal linking bridges in hydrogel networks, the prepared conductive hydrogel is not only repairable at room temperature, but also recyclable.

Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study.

BACKGROUND: Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC. RESULTS: Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = - 0.75, P < 0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, a minority of limited RPC patients progressed into systemic form. Patients with Ear pattern had the highest survival rate and relatively lower inflammatory status. CONCLUSIONS: RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement. The clinical patterns and presenting forms may evolve during follow-up. Our findings may facilitate early recognition of this rare disease.

IL­27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma.

Type 2 cytokine­associated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL­27) has been reported as an initiator and suppressor of T­helper 1 (Th1) and T­helper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL­27. Total and differential cell counts were determined from Wright­Giemsa­stained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATA­binding protein­3 (GATA3) and T­bet (T­box transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL­27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL­27 prevented airway remodeling in a chronic model of asthma. Following administration of IL­27, the mRNA expression levels of STAT1 and T­bet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL­27 ameliorated Th2­related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.

Diagnosing relapsing polychondritis remains a common challenge: experience from a Chinese retrospective cohort.

OBJECTIVE: The diagnosis of relapsing polychondritis (RP) is often mistaken or delayed. In this retrospective cohort, we aimed to unveil the causes responsible for such phenomenon, to determine the associated factors, and to compare diagnosis in clinical settings with the current diagnostic criteria. METHOD: Eighty-seven RP patients followed-up by rheumatologists from January 1, 2008, to October 31, 2018, were retrospectively analyzed. RESULTS: A total of 50 male and 37 female patients were included with a mean age of 45.9 ± 14.5 years. Ninety-three percent were initially admitted by non-rheumatologic specialists .Twenty-eight percent were correctly diagnosed, while 72% were misdiagnosed at the first visits, all by non-rheumatologic specialists. Patients admitted by non-rheumatologic specialists had increased odds of misdiagnosis (odds ratio [OR] = 1.3, 95% confidence interval [95% CI] 1.1-1.7, P = 0.000). Fifty-seven (65.5%) patients did not meet with Michet or Damiani criteria, with 16 (18.4%) patients diagnosed as partial RP and 41( 47.1%) patients diagnosed as limited RP. CONCLUSIONS: Incorrect and delayed diagnosis of RP is common in our cohort, and insufficient awareness of the disease in non-rheumatologic specialists at least partially contributes to this. It is imperative to revise the current criteria for early diagnosis.Key Points• Diagnosing relapsing polychondritis (RP) in early stage remains challenging after all these years, especially among non-rheumatologic specialists, indicating the importance of teaching non-rheumatologic specialists to improve their understanding of this rare disease.• Many RP patients did not fully meet with the current criteria, suggesting that revision of the current criteria is imperative for early diagnosis of this rare disease.

Reliability and validity of the Chinese version of the Scale for Assessment and Rating of Ataxia.

BACKGROUND: The Scale for the Assessment and Rating of Ataxia (SARA) was shown to be a reliable and valid measurement for patients with spinocerebellar ataxia (SCA). The Brazilian version and the Japanese version of SARA were favorable for good reliability and validity. This study aimed to translate SARA into Chinese and test its reliability and validity in measurement of cerebellar ataxia. METHODS: SARA was translated into Chinese. A total 39 patients with degeneration cerebellar ataxia were evaluated independently by two neurologists with the Chinese version of SARA. Then the patients were evaluated by one of above neurologists with International Cooperative Ataxia Rating Scale (ICARS). The statistical analyses were performed using SPSS 17.0 for Windows. RESULTS: The Cronbach's alpha coefficient of the Chinese version of SARA was 0.78, which represents a good internal consistence. The correlation coefficient of the Chinese version of SARA scores between the two evaluators was 0.86, illustrating that the inter-rater reliability of Chinese version of SARA was good. The correlation coefficient between the Chinese version of SARA and ICARS was 0.91, illustrating that the criterion validity of Chinese version of SARA was not bad. CONCLUSIONS: The Chinese version of SARA is reliable and effective for the assessment of degeneration cerebellar ataxia. Compared with ICARS, the evaluation of Chinese version of SARA is more objective, the assessment time is shortened, and the maneuverability is better.

[Construction of a recombinant BAC-HSV-1 strain HF with a GFP reporter gene and characterization of its infectious progeny virus].

To construct the plasmid of BAC-HSV-1 with GFP reporter gene and research the biological property of its infectious progeny virus. We constructed the plasmid C223-UL43-left-arms-UL47-right-arms which carried the homologous sequences of HSV-1. Liposome embedding method was used to transfect HSV-1 genome and the plasmid C223-UL43-left-arms-UL47-right-arms linearized by Mlu I digestion into Vero cells. After the successful homologous recombination in the eukaryotic cells, the recombinant BAC-HSV-1 with GFP reporter gene was generated. Then, the positive CPE were taken by plaque purification and by hirt extraction during the moment of the circularization of HSV-1 DNA, and the plasmid of BAC -HSV-1 was acquired. Electroporation was used to transfect the BAC -HSV-1 into DH10B, and then the single colonies of interest were confirmed both by MluI digestion and PCR. Experimental group and the control group cells were given BAC-HSV-1 plasmid and HSV-1 genomic DNA respectively to produce the BAC-HSV-1 and HSV-1 progeny virions. Vero cells were inoculated with the progeny virions at MOI = 0.1 and then a TCID50 assay was performed to determine the titers of virons in the two groups at 48 hours post inoculation. The plasmid BAC-HSV-1 was successfully constructed by the restriction enzyme analysis and the PCR. The titers of progeny virions were calculated by the TCID50 assay. No significant difference in the titers of virions between two groups was observed (P > 0.05). The infectious BAC-HSV-1 shuttle virus/plasmid between eukaryotic and prokaryotic cells was successfully constructed.

[Construction of the HSV-1 strain HF amplicon and study on its unversal function between different HSV serotypes].

The study aimed to construct the amplicon vector of HSV-1 strain HF and explore its universal package function between different serotypes of HSV. OriS and pac elements were obtained by enzyme digestion from the Plasmid BAC-HSV-1 strain HF and sequenced. With red fluorescence (DsRed) as a reporter gene, the amplicon vector of HSV-1 strain HF was constructed based on pSilencer2.0-U6. The amplicon vector was transfected into Vero cells by lipofectamine 2000, then packaged by HSV-1 strain HF and HSV-2 strain HG52 as helper virus separately. The supernatant was collected after cytopathic effect. Red fluorescence was observed in Vero cells reinfected by the supernatant. In this study,the amplicon vector of HSV-1 strain HF was successfully constructed and it could be packaged by HSV-1 strain HF and HSV-2 strainHG52.