Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease.

BACKGROUND: Although increasing studies have reported that dose escalation can improve treatment response to ustekinumab in patients with Crohn's disease (CD), their strategies mainly focus on maintenance regimen. Evidence of ustekinumab dose escalation in induction regimen, particularly in severe CD, remains limited. This study evaluated the efficacy and safety of intravenous ustekinumab with 2 initial doses in patients with severely active CD. METHODS: A retrospective observational study of 99 adult patients with severe CD treated with ustekinumab from 3 IBD centers included 48 patients with standard and 51 with optimized induction treatment. Clinical outcomes, inflammatory biomarkers including fecal calprotectin (FC) normalization, and endoscopic outcomes were evaluated at weeks 16 and 48. Adverse events and treatment decisions after initial induction were also collected. RESULTS: Compared with the standard group, 2 initial intravenous injections of ustekinumab achieved higher clinical response (92.2%, 47 of 51, P = .656), clinical remission (88.2%, 45 of 51, P = .221), endoscopic response (75.8%, 25 of 33, P = .125), and FC normalization (70.6%, 36 of 51, P = .138) at week 16. The mucosal healing rate at week 16 (63.6%, P = .022) was statistically higher in the optimization group. At week 48, patients with optimized treatment achieved higher clinical response (80.4%, 41 of 51, P = .003), clinical remission (70.6%, 36 of 51, P = .007), FC normalization (66.7%, 34 of 51, P = .031), endoscopic response (72.7%, 24 of 33, P = .006), and mucosal healing (57.6%, 19 of 33, P = .004). At the last follow-up, 82.4% of optimally treated patients adhered to continued treatment with ustekinumab (P < .001). CONCLUSIONS: Optimization of ustekinumab by 2 initial intravenous inductions is more effective than standard therapy for adult patients with severe CD.

This study used an optimization strategy in severe adult Crohn's disease with 2 initial intravenous doses of ustekinumab. This new strategy proved to be effective and safe.

Differences in clinical characteristics and liver injury between patients diagnosed with the Omicron subvariant BA.5.2 and the prototype of SARS-CoV-2: a single center retrospective study.

BACKGROUND: The purpose of this study was to investigate the differences between the clinical characteristics and the factors influencing liver injury in patients with the Omicron subvariant BA.5.2 (Omicron BA.5.2) and the prototype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Between December 30, 2019 and November 30, 2022, 157 patients infected with the SARS-CoV-2 prototype and 199 patients infected with the Omicron BA.5.2 were included in this case-control, single-center, retrospective study. Differences in clinical characteristics and liver injury between the Omicron BA.5.2 patients and the prototype patients were subsequently analyzed. RESULTS: None of the Omicron BA.5.2 patients reached the critical state, and showed relatively milder symptoms including fever, cough, headache, muscle soreness, nausea or vomiting, diarrhea, anorexia and hypoxia. The Omicron BA.5.2 had a lower effect on body temperature (T), white blood cell (WBC) count, hematocrit (HCT), C-reactive protein (CRP) level, D-dimer, finger pulse oxygen saturation (SpO2) and lung lesions. The differences in liver injury between the two groups were related to the severity of the disease, T, blood oxygen levels, albumin (ALB), CRP, and medication usage. Gender, body mass index, and CRP levels influenced liver damage in the Omicron BA.5.2 patients. In particular, CRP was an independent risk factor for liver injury. Because the severity of liver function damage was considerably low, only a small number of Omicron BA.5.2 patients required liver-protective treatment. CONCLUSION: Liver injury is expected in the COVID-19 patients. The Omicron BA.5.2 patients showed milder symptoms of liver injury than the prototype patients. However, dynamic monitoring of liver function is warranted, especially for individuals presenting with elevated levels of CRP.

[Management of Obstructive Sleep Apnea Syndrome during the Coronavirus Disease 2019 Pandemic].

The coronavirus disease 2019(COVID-19) pandemic poses a severe threat to global health.As an emerging infectious disease mainly attacking the respiratory tract,it has severely challenged the management of chronic non-infectious respiratory diseases including obstructive sleep apnea(OSA) and asthma.This article reviews the impact of OSA on the incidence of COVID-19 and the underlying pathophysiological mechanism,as well as the effects of OSA on the hospitalization risk and the prognosis and outcome of COVID-19 patients,which will provide novel ideas for the management of OSA during the COVID-19 pandemic.

Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq.

Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon compound, is a carcinogen that causes head and neck cancers. Despite intensive research, the molecular mechanism of BaP in the development of oral squamous cell carcinoma (OSCC) remains largely unknown. In the present study, the SCC-9 human OSCC cell line was cultured in vitro, separated into treatment groups, and treated with dimethyl sulfoxide or BaP at various concentrations. The malignant behavior ascribed to the BaP treatment was investigated by cell proliferation, clony formation assay, and Transwell assays. Furthermore, transcriptome sequencing was performed to detect the differentially expressed genes, followed by quantitative real-time PCR to measure the expression levels of nine of these genes. Moreover, the Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed the biological processes and signaling pathways in which the target genes were involved. Significant effects on SCC-9 cell proliferation, tumorigenicity, cell migration, and invasion were observed after exposure to 8 µM BaP. Additional results revealed that BaP inhibited apoptosis in a dose-dependent manner. The transcriptome sequencing results showed 137 upregulated genes and 135 downregulated genes induced by BaP, associated with tumor-related biological processes and signaling pathways, mainly including transcriptional dysregulation in cancer, the tumor necrosis factor signaling pathway, metabolism of xenobiotics by cytochrome P450, mitogen-activated protein kinase signaling pathway, and so forth. Our study demonstrates that BaP may regulate the expression of certain genes involved in tumor-associated signaling pathways, thereby promoting the proliferative, tumorigenic, and metastatic behaviors of OSCC cells while suppressing their apoptosis.

Comprehensive Analysis of Sinonasal Inverted Papilloma Expression Profiles Identifies Long Non-Coding RNA AKTIP as a Potential Biomarker.

Long noncoding RNAs (lncRNAs) are a novel class of potential biomarkers and therapeutic targets for the treatment of neoplasms. The purpose of this study was to explore the expression profile, potential functions, and diagnostic and clinical significance of lncRNAs in sinonasal inverted papilloma (SNIP). The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods. Microarray analysis identified 1,668 significantly upregulated and 1,767 downregulated lncRNAs in SNIP. Several mRNAs coexpressed with lncRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Lnc-AKTIP might interact with a variety of tumor-associated proteins and transcription factors, such as PCBP2, IRF-1, and p53. Receiver operating characteristic curve analysis for lnc-AKTIP showed an area under the curve of 0.939. Notably, its expression level was significantly decreased in SNIP tissues versus normal tissues and was associated with SNIP staging. Lnc-AKTIP may serve as a valuable diagnostic biomarker and a therapeutic target for SNIP.

Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis

Exosomes are the mediators of intercellular signal transduction, and they have been involved in the carcinogenesis and chemoresistance of tumor cells. Herein, we intended to investigate whether circular RNA (circRNA) circ_0006174 can regulate chemoresistance of doxorubicin (DOX) in colorectal cancer via exosomes. Forty-one pairs of normal and CRC (DOX sensitive, n = 16; DOX resistant, n = 25) samples were collected. The resistant cell lines (LoVo/DOX and HCT116/DOX) were constructed by exposure of parental cell lines (LoVo and HCT116) to DOX. The detection of circ_0006174, microRNA-1205 (miR-1205), and cyclin D2 (CCND2) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8(CCK-8) was applied for determining the half of inhibitory concentration (IC50) of DOX and cell proliferation. The migration and invasion capacities were analyzed via transwell assay. Exosomes were extracted using ultracentrifugation. Protein levels were determined using western blot. Dual-luciferase reporter assay was used for affirming target interaction. In vivo experiment was performed by establishing xenograft models in mice. Circ_0006174 level was upregulated in DOX-resistant CRC tissues and cells. The downregulation of circ_0006174 inhibited DOX resistance, cell proliferation, migration, and invasion in DOX-resistant CRC cells. Interestingly, the abundant circ_0006174 was enriched in exosomes derived from DOX-resistant CRC cells. Furthermore, circ_0006174 could enhance DOX resistance via the exosomal intercellular transfer. Moreover, we validated the target relation of circ_0006174/miR-1205 or miR-1205/CCND2. The effect of exosomal circ_0006174 on DOX resistance was achieved by upregulating the miR-1205-mediated CCND2. In vivo, knockdown of circ_0006174 also enhanced tumor sensitivity to DOX by targeting miR-1205/CCND2 axis. (AU)

Exosomal transfer of circ_0006174 contributes to the chemoresistance of doxorubicin in colorectal cancer by depending on the miR-1205/CCND2 axis.

Exosomes are the mediators of intercellular signal transduction, and they have been involved in the carcinogenesis and chemoresistance of tumor cells. Herein, we intended to investigate whether circular RNA (circRNA) circ_0006174 can regulate chemoresistance of doxorubicin (DOX) in colorectal cancer via exosomes. Forty-one pairs of normal and CRC (DOX sensitive, n = 16; DOX resistant, n = 25) samples were collected. The resistant cell lines (LoVo/DOX and HCT116/DOX) were constructed by exposure of parental cell lines (LoVo and HCT116) to DOX. The detection of circ_0006174, microRNA-1205 (miR-1205), and cyclin D2 (CCND2) was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8(CCK-8) was applied for determining the half of inhibitory concentration (IC50) of DOX and cell proliferation. The migration and invasion capacities were analyzed via transwell assay. Exosomes were extracted using ultracentrifugation. Protein levels were determined using western blot. Dual-luciferase reporter assay was used for affirming target interaction. In vivo experiment was performed by establishing xenograft models in mice. Circ_0006174 level was upregulated in DOX-resistant CRC tissues and cells. The downregulation of circ_0006174 inhibited DOX resistance, cell proliferation, migration, and invasion in DOX-resistant CRC cells. Interestingly, the abundant circ_0006174 was enriched in exosomes derived from DOX-resistant CRC cells. Furthermore, circ_0006174 could enhance DOX resistance via the exosomal intercellular transfer. Moreover, we validated the target relation of circ_0006174/miR-1205 or miR-1205/CCND2. The effect of exosomal circ_0006174 on DOX resistance was achieved by upregulating the miR-1205-mediated CCND2. In vivo, knockdown of circ_0006174 also enhanced tumor sensitivity to DOX by targeting miR-1205/CCND2 axis. Altogether, these findings unraveled that circ_0006174-enriched exosomes elevated DOX chemoresistance in CRC by the miR-1205/CCND2 axis. The exosomal circ_0006174 can be used as an available biomarker for the diagnosis of chemoresistance in CRC.

[An Extrapulmonary Manifestation of Coronavirus Disease 2019:Olfactory Dysfunction].

In addition to acute respiratory symptoms,coronavirus disease 2019(COVID-19)could cause olfactory dysfunction,which becomes the only clinical manifestation of COVID-19 in some cases.We review the epidemiological characteristics,pathological mechanism,screening value,treatment and prognosis of olfactory dysfunction in patients with COVID-19,aiming to achieve an in-depth understanding of the early diagnosis,quarantine,scientific treatment and prognosis of COVID-19.

The Symptoms and Medications of Patients with Inflammatory Bowel Disease in Hubei Province after COVID-19 Epidemic.

OBJECTIVES: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. METHODS: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. RESULTS: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. CONCLUSIONS: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.

Sparse Logistic Regression With L 1/2 Penalty for Emotion Recognition in Electroencephalography Classification.

Emotion recognition based on electroencephalography (EEG) signals is a current focus in brain-computer interface research. However, the classification of EEG is difficult owing to large amounts of data and high levels of noise. Therefore, it is important to determine how to effectively extract features that include important information. Regularization, one of the effective methods for EEG signal processing, can effectively extract important features from the signal and has potential applications in EEG emotion recognition. Currently, the most popular regularization technique is Lasso (L 1) and Ridge Regression (L 2). In recent years, researchers have proposed many other regularization terms. In theory, L q -type regularization has a lower q value, which means that it can be used to find solutions with better sparsity. L 1/2 regularization is of L q type (0 < q < 1) and has been shown to have many attractive properties. In this work, we studied the L 1/2 penalty in sparse logistic regression for three-classification EEG emotion recognition, and used a coordinate descent algorithm and a univariate semi-threshold operator to implement L 1/2 penalty logistic regression. The experimental results on simulation and real data demonstrate that our proposed method is better than other existing regularization methods. Sparse logistic regression with L 1/2 penalty achieves higher classification accuracy than the conventional L 1, Ridge Regression, and Elastic Net regularization methods, using fewer but more informative EEG signals. This is very important for high-dimensional small-sample EEG data and can help researchers to reduce computational complexity and improve computational accuracy. Therefore, we propose that sparse logistic regression with the L 1/2 penalty is an effective technique for emotion recognition in practical classification problems.

Ultrasound-modulated laser feedback tomography in the reflective mode.

A novel method of ultrasound-modulated optical tomography (UOT) detection based on the laser feedback technology is proposed in this Letter. The system has advantages such as a simple structure, high sensitivity, and reflective configuration. Effective penetration depths of up to 9 cm and 5 cm in phantom and biological tissues, respectively, have been demonstrated experimentally. The detection capability is comparable with the state of the art in the transmission mode but with a much lower photon consumption. Although a lot remains to be improved, the proposed method is promising for further development toward practical applications.

Depth of focus extension by filtering in the frequency domain in laser frequency-shifted feedback imaging.

The depth of focus extension in optical imaging is of considerable interest. In this paper, a laser frequency-shifted feedback scanning imaging configuration is demonstrated whose depth of focus is greatly extended through numerical filtering. The transmission characteristics of the system are studied. The original image is acquired through a two-dimensional scanning point by point with the target placed on a defocused plane. Filtered in the frequency domain, images on any oriented plane can be refocused. The superior performances are presented by imaging a three-dimensional target, and the process of gradual refocusing is demonstrated. To obtain the maximum extension in the depth of defocus, a series of numerical experiments has been carried out, which reveals its depth of focus is capable of being extended to four times the length of the objective focus length. The fabulous performances can motivate three-dimensional surface profile measurement.

Ultrasound modulated laser confocal feedback imaging inside turbid media.

Ultrasound modulated laser confocal feedback technology is proposed in the imaging inside turbid media. By selecting the detectable signal photons and rejecting the background noise photons in the frequency domain based on the ultrasound modulation, the signal-to-noise ratio (SNR) can be much improved, especially in the turbid media, compared with the traditional imaging without ultrasound modulation. This is a promising method to reach both a larger penetration depth and a better SNR than other optical methods.

Anatomical and functional volume concordance between FDG PET, and T2 and diffusion-weighted MRI for cervical cancer: a hybrid PET/MR study.

PURPOSE: To evaluate the concordance among (18)F-FDG PET imaging, MR T2-weighted (T2-W) imaging and apparent diffusion coefficient (ADC) maps with diffusion-weighted (DW) imaging in cervical cancer using hybrid whole-body PET/MR. METHODS: This study prospectively included 35 patients with cervical cancer who underwent pretreatment (18)F-FDG PET/MR imaging. (18)F-FDG PET and MR images were fused using standard software. The percent of the maximum standardized uptake values (SUV max) was used to contour tumours on PET images, and volumes were calculated automatically. Tumour volumes measured on T2-W and DW images were calculated with standard techniques of tumour area multiplied by the slice profile. Parametric statistics were used for data analysis. RESULTS: FDG PET tumour volumes calculated using SUV max (14.30 ± 4.70) and T2-W imaging volume (33.81 ± 27.32 cm(3)) were similar (P > 0.05) at 35 % and 40 % of SUV max (32.91 ± 18.90 cm(3) and 27.56 ± 17.19 cm(3) respectively) and significantly correlated (P < 0.001; r = 0.735 and 0.766). The mean DW volume was 30.48 ± 22.41 cm(3). DW volumes were not significantly different from FDG PET volumes at either 35 % SUV max or 40 % SUV max or from T2-W imaging volumes (P > 0.05). PET subvolumes with increasing SUV max cut-off percentage showed an inverse change in mean ADC values on DW imaging (P < 0.001, ANOVA). CONCLUSION: Hybrid PET/MR showed strong volume concordance between FDG PET, and T2-W and DW imaging in cervical cancer. Cut-off at 35 % or 40 % of SUV max is recommended for (18)F-FDG PET/MR SUV-based tumour volume estimation. The linear tumour subvolume concordance between FDG PET and DW imaging demonstrates individual regional concordance of metabolic activity and cell density.