Agonist of growth hormone-releasing hormone improves the disease features of spinal muscular atrophy mice.

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disease affecting children and young adults, caused by mutations of the survival motor neuron 1 gene (SMN1). SMA is characterized by the degeneration of spinal alpha motor neurons (αMNs), associated with muscle paralysis and atrophy, as well as other peripheral alterations. Both growth hormone-releasing hormone (GHRH) and its potent agonistic analog, MR-409, exert protective effects on muscle atrophy, cardiomyopathies, ischemic stroke, and inflammation. In this study, we aimed to assess the protective role of MR-409 in SMNΔ7 mice, a widely used model of SMA. Daily subcutaneous treatment with MR-409 (1 or 2 mg/kg), from postnatal day 2 (P2) to euthanization (P12), increased body weight and improved motor behavior in SMA mice, particularly at the highest dose tested. In addition, MR-409 reduced atrophy and ameliorated trophism in quadriceps and gastrocnemius muscles, as determined by an increase in fiber size, as well as upregulation of myogenic genes and inhibition of proteolytic pathways. MR-409 also promoted the maturation of neuromuscular junctions, by reducing multi-innervated endplates and increasing those mono-innervated. Finally, treatment with MR-409 delayed αMN death and blunted neuroinflammation in the spinal cord of SMA mice. In conclusion, the present study demonstrates that MR-409 has protective effects in SMNΔ7 mice, suggesting that GHRH agonists are promising agents for the treatment of SMA, possibly in combination with SMN-dependent strategies.

GHRH agonist MR-409 protects ß-cells from streptozotocin-induced diabetes.

Patients with type 1 diabetes (T1D) suffer from insufficient functional ß-cell mass, which results from infiltration of inflammatory cells and cytokine-mediated ß-cell death. Previous studies demonstrated the beneficial effects of agonists of growth hormone-releasing hormone receptor (GHRH-R), such as MR-409 on preconditioning of islets in a transplantation model. However, the therapeutic potential and protective mechanisms of GHRH-R agonists on models of T1D diabetes have not been explored. Using in vitro and in vivo models of T1D, we assessed the protective propertie of the GHRH agonist, MR409 on ß-cells. The treatment of insulinoma cell lines and rodent and human islets with MR-409 induces Akt signaling by induction of insulin receptor substrate 2 (IRS2), a master regulator of survival and growth in ß-cells, in a PKA-dependent manner. The increase in cAMP/PKA/CREB/IRS2 axis by MR409 was associated with decrease in ß-cell death and improved insulin secretory function in mouse and human islets exposed to proinflammatory cytokines. The assessment of the effects of GHRH agonist MR-409 in a model of T1D induced by low-dose streptozotocin showed that mice treated with MR-409 exhibited better glucose homeostasis, higher insulin levels, and preservation of ß-cell mass. Increased IRS2 expression in ß-cells in the group treated with MR-409 corroborated the in vitro data and provided evidence for the underlying mechanism responsible for beneficial effects of MR-409 in vivo. Collectively, our data show that MR-409 is a novel therapeutic agent for the prevention and treatment of ß-cells death in T1D.

vPIF-1 is an insulin-like antiferroptotic viral peptide.

Iridoviridae, such as the lymphocystis disease virus-1 (LCDV-1) and other viruses, encode viral insulin-like peptides (VILPs) which are capable of triggering insulin receptors (IRs) and insulin-like growth factor receptors. The homology of VILPs includes highly conserved disulfide bridges. However, the binding affinities to IRs were reported to be 200- to 500-fold less effective compared to the endogenous ligands. We therefore speculated that these peptides also have noninsulin functions. Here, we report that the LCDV-1 VILP can function as a potent and highly specific inhibitor of ferroptosis. Induction of cell death by the ferroptosis inducers erastin, RSL3, FIN56, and FINO2 and nonferroptotic necrosis produced by the thioredoxin-reductase inhibitor ferroptocide were potently prevented by LCDV-1, while human insulin had no effect. Fas-induced apoptosis, necroptosis, mitotane-induced cell death and growth hormone-releasing hormone antagonist-induced necrosis were unaffected, suggesting the specificity to ferroptosis inhibition by the LCDV-1 VILP. Mechanistically, we identified the viral C-peptide to be required for inhibition of lipid peroxidation and ferroptosis inhibition, while the human C-peptide exhibited no antiferroptotic properties. In addition, the deletion of the viral C-peptide abolishes radical trapping activity in cell-free systems. We conclude that iridoviridae, through the expression of insulin-like viral peptides, are capable of preventing ferroptosis. In analogy to the viral mitochondrial inhibitor of apoptosis and the viral inhibitor of RIP activation (vIRA) that prevents necroptosis, we rename the LCDV-1 VILP a viral peptide inhibitor of ferroptosis-1. Finally, our findings indicate that ferroptosis may function as a viral defense mechanism in lower organisms.

Growth hormone-releasing hormone receptor antagonist MIA-602 attenuates cardiopulmonary injury induced by BSL-2 rVSV-SARS-CoV-2 in hACE2 mice.

COVID-19 pneumonia causes acute lung injury and acute respiratory distress syndrome (ALI/ARDS) characterized by early pulmonary endothelial and epithelial injuries with altered pulmonary diffusing capacity and obstructive or restrictive physiology. Growth hormone-releasing hormone receptor (GHRH-R) is expressed in the lung and heart. GHRH-R antagonist, MIA-602, has been reported to modulate immune responses to bleomycin lung injury and inflammation in granulomatous sarcoidosis. We hypothesized that MIA-602 would attenuate rVSV-SARS-CoV-2-induced pulmonary dysfunction and heart injury in a BSL-2 mouse model. Male and female K18-hACE2tg mice were inoculated with SARS-CoV-2/USA-WA1/2020, BSL-2-compliant recombinant VSV-eGFP-SARS-CoV-2-Spike (rVSV-SARS-CoV-2), or PBS, and lung viral load, weight loss, histopathology, and gene expression were compared. K18-hACE2tg mice infected with rVSV-SARS-CoV-2 were treated daily with subcutaneous MIA-602 or vehicle and conscious, unrestrained plethysmography performed on days 0, 3, and 5 (n = 7 to 8). Five days after infection mice were killed, and blood and tissues collected for histopathology and protein/gene expression. Both native SARS-CoV-2 and rVSV-SARS-CoV-2 presented similar patterns of weight loss, infectivity (~60%), and histopathologic changes. Daily treatment with MIA-602 conferred weight recovery, reduced lung perivascular inflammation/pneumonia, and decreased lung/heart ICAM-1 expression compared to vehicle. MIA-602 rescued altered respiratory rate, increased expiratory parameters (Te, PEF, EEP), and normalized airflow parameters (Penh and Rpef) compared to vehicle, consistent with decreased airway inflammation. RNASeq followed by protein analysis revealed heightened levels of inflammation and end-stage necroptosis markers, including ZBP1 and pMLKL induced by rVSV-SARS-CoV-2, that were normalized by MIA-602 treatment, consistent with an anti-inflammatory and pro-survival mechanism of action in this preclinical model of COVID-19 pneumonia.

Fast simulation for interacting four-level Rydberg atoms: electromagnetically induced transparency and Autler-Townes splitting.

Quantum sensing using Rydberg atoms is an emerging technology for precise measurement of electric fields. However, most existing computational methods are all based on a single-particle model and neglect Rydberg-Rydberg interaction between atoms. In this study, we introduce the interaction term into the conventional four-level optical Bloch equations. By incorporating fast iterations and solving for the steady-state solution efficiently, we avoid the computation of a massive 4N × 4N dimensional matrix. Additionally, we apply the Doppler frequency shift to each atom used in the calculation, eliminating the requirement for an additional Doppler iteration. These schemes allow for the calculation of the interaction between 7000 atoms around one minute. Based on the many-body model, we investigate the Rydberg-Rydberg interaction of Rydberg atoms under different atomic densities. Furthermore, we compare our results with the literature data of a three-level system and the experimental results of our own four-level system. The results demonstrate the validity of our model, with an effective error of 4.59% compared to the experimental data. Finally, we discover that the many-body model better predicts the linear range for measuring electric fields than the single-particle model, making it highly applicable in precise electric field measurements.

Wavelength division multiplexing based on the coupling effect of helical edge states in two-dimensional dielectric photonic crystals.

Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.

High-Q metasurface signal isolator for 1.5T surface coil magnetic resonance imaging on the go.

The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-resolution MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners.

Isolation of Non-Tuberculous Mycobacteria (NTM) from Household Water of Patients with NTM Pulmonary Disease.

Objective: This study aims to investigate the prevalence of NTM in household water in China and assess its potential role as a source of infection for NTM pulmonary disease, a crucial step for understanding and controlling the spread of this increasingly prevalent disease. Methods: To examine the prevalence of mycobacteria in household water, 500 mL water samples and swabs were collected from all taps of 19 patients' homes. The amplification of mycobacterial 16SrRNA with bacteriological identification was as a protocol to discriminate mycobacterial isolations from non- mycobacterial isolations. The 570bp 16SrRNA amplicon was sequenced and used to define mycobacterial species. Results: The mycobacteria isolated from clinical samples from 19 patients included M. intracellulare, M. avium, M. abscessus, and M. kansasii. NTM isolated from household water of patients included M. avium (1 case), M. abscessus (2 cases), M. kansasii (8 cases), M. gordonae (1 case), M. gilvum (1 case), M. fortuitum (1 case), M. porcinum (1 case). M. abscessus, M. kansasii, and M. avium causing human disease were isolated from household water. Though M. intracellulare was the predominant species isolated from patients with NTM pulmonary disease, it was not found in household water. In addition, our results revealed that NTM preferentially colonize in biofilm/sediment (75% of positive growths were from tap swab samples), indicating the significance of finding specific NTM species in household water in relation to the patients' conditions, or the lack of correlation between M. intracellulare in patients and its absence in household water. Conclusions: The isolation of pathogenic NTM species from household water underscores the critical role of water hygiene in preventing NTM pulmonary disease and highlights the need for targeted public health strategies.

Assessing trends in breast care surveillance metrics after implementing surgeon-specific tracking and performance reporting in a large, integrated cancer network.

BACKGROUND: There are few quality metrics and benchmarks specific to surgical oncology. Development of a surgeon-level performance metrics system based on peer comparisons is hypothesized to positively influence surgical decision-making. This study established a tracking and reporting system comprised of evidence and consensus-based metrics to assess breast care delivered by individual surgeons. METHODS: Surgeons' performance is assessed by a surveillance tracking system of metrics pertaining to referrals and surgical elements. This retrospective analysis of prospectively collected breast care data reports on recurring 6-month and cumulative data from nine care locations from 2015 to 2021. RESULTS: Breast care was provided to 6659 patients by 41 surgeons. A total of 27 breast care metrics were evaluated over 7 years. Metrics with consistent, proficient results were retired after 18 months, including the rate of core biopsy, specimen orientation, and referrals to medical oncology, genetics, and fertility, among others. In clinically node-negative, hormone receptor-positive patients 70 years of age or older, the cumulative rate of sentinel lymph node (SLN) biopsy significantly decreased by 40% over 5.5 years (p < .001). The overall breast conservation rate for T0-T2 cancer increased 10% over 7 years. At the surgeon level, improvements were made in the median number of SLNs removed and in operative note documentation. CONCLUSIONS: Implementation of a surgeon-specific, peer comparison-based metric and tracking system has yielded substantive changes in breast care management. This process and governance structure can serve as a model for quantification of breast care at other institutions and for other disease sites.

Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.

BACKGROUND: The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). METHODS: A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. RESULTS: For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively. CONCLUSION: The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.

Efficacy of a growth hormone-releasing hormone agonist in a murine model of cardiometabolic heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major unmet medical need owing to its diverse pathophysiology and lack of effective therapies. Potent synthetic, agonists (MR-356 and MR-409) of growth hormone-releasing hormone (GHRH) improve the phenotype of models of HF with reduced ejection fraction (HFrEF) and in cardiorenal models of HFpEF. Endogenous GHRH exhibits a broad range of regulatory influences in the cardiovascular (CV) system and aging and plays a role in several cardiometabolic conditions including obesity and diabetes. Whether agonists of GHRH can improve the phenotype of cardiometabolic HFpEF remains untested and unknown. Here we tested the hypothesis that MR-356 can mitigate/reverse the cardiometabolic HFpEF phenotype. C57BL6N mice received a high-fat diet (HFD) plus the nitric oxide synthase inhibitor (l-NAME) for 9 wk. After 5 wk of HFD + l-NAME regimen, animals were randomized to receive daily injections of MR-356 or placebo during a 4-wk period. Control animals received no HFD + l-NAME or agonist treatment. Our results showed the unique potential of MR-356 to treat several HFpEF-like features including cardiac hypertrophy, fibrosis, capillary rarefaction, and pulmonary congestion. MR-356 improved cardiac performance by improving diastolic function, global longitudinal strain (GLS), and exercise capacity. Importantly, the increased expression of cardiac pro-brain natriuretic peptide (pro-BNP), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor-A (VEGF-A) was restored to normal levels suggesting that MR-356 reduced myocardial stress associated with metabolic inflammation in HFpEF. Thus, agonists of GHRH may be an effective therapeutic strategy for the treatment of cardiometabolic HFpEF phenotype.NEW & NOTEWORTHY This randomized study used rigorous hemodynamic tools to test the efficacy of a synthetic GHRH agonist to improve cardiac performance in a cardiometabolic HFpEF. Daily injection of the GHRH agonist, MR-356, reduced the HFpEF-like effects as evidenced by improved diastolic dysfunction, reduced cardiac hypertrophy, fibrosis, and pulmonary congestion. Notably, end-diastolic pressure and end-diastolic pressure-volume relationship were reset to control levels. Moreover, treatment with MR-356 increased exercise capacity and reduced myocardial stress associated with metabolic inflammation in HFpEF.

Effect of Delayed Oncoplastic Reduction Mammoplasty on Radiation Treatment Delay Following Breast-Conserving Surgery for Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the delay in initiating adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer who underwent oncoplastic reduction mammoplasty (ORM) following BCS compared with a matched cohort of patients who did not undergo ORM between BCS and RT. METHODS: Medical records of 112 women (56 ORMs and 56 matched non-ORMs) with carcinoma in situ or early-stage breast cancer treated with BCS were reviewed. ORM was performed in a delayed manner following BCS, allowing confirmation of negative surgical margins. Time to RT was defined as time from last oncologic surgery to start of RT. RESULTS: The median follow-up time was 6.8 years for the ORM cohort and 6.7 years for the control non-ORM cohort. Patients who underwent ORM following BCS experienced a significant delay in initiating RT (>8 weeks) than matched patients not undergoing ORM (66% vs. 34%; p < 0.001). Wound complications occurred in 44.6% (n = 25) of patients in the ORM cohort, which were mostly minor, including delayed wound healing and/or infection (39%). There was no significant difference in local recurrence between patients in the non-ORM and ORM cohorts (p = 0.32). CONCLUSIONS: This study demonstrates that ORM following BCS has the potential to delay RT >8 weeks, largely as a result of increased risk of wound complications; however, this delay did not impact local control. ORM can be safely considered for appropriately selected patients with breast cancer.

Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection.

Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio-synthetical target for anti-tuberculosis (TB) drug development. Here, we report that mycobacterial AG is recognized by galectin-9 and exacerbates mycobacterial infection. Administration of AG-specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb-infected mice or Mycobacterium marinum-infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin-9 with high affinity, and galectin-9 associates with transforming growth factor ß-activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal-regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin-9 or inhibition of MMPs blocks AG-induced pathological impairments in the lung, and the AG-galectin-9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin-9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.

Diagnostic performance of metagenomic next-generation sequencing in non-tuberculous mycobacterial pulmonary disease when applied to clinical practice.

OBJECTIVE: To compare non-tuberculous mycobacterial pulmonary disease (NTMPD) diagnosis by metagenomic next-generation sequencing (mNGS) with Bactec mycobacterial growth indicator tube (MGIT) 960. METHODS: A total of 422 patients with suspected NTMPD in Shanghai Pulmonary Hospital between January 2020 and May 2021 were retrospectively analyzed; 194 were diagnosed with NTMPD. The diagnostic performance of mNGS and MGIT 960 for NTMPD was assessed. Receiver operating characteristic (ROC) curves and areas under curve (AUCs) were compared. RESULTS: The sensitivity of mNGS in NTMPD diagnosis was 81.4% and higher than that of MGIT 960 (53.6%). The specificity of mNGS in NTMPD diagnosis was 97.8%, similar to that of MGIT 960 (100%). The sensitivity of combined mNGS and MGIT 960 in NTMPD diagnosis was 91.8%. The sensitivity of mNGS for bronchoalveolar lavage fluid (BALF), pulmonary puncture tissue fluid, and sputum was 84.8%, 80.6%, and 77.5%, respectively; all were higher than that of MGIT 960 (P < 0.05). The AUC of mNGS and MGIT 960 was 0.897 and 0.768, respectively. The AUC of mNGS were BALF (0.916), pulmonary puncture tissue fluid (0.903), and sputum (0.870). CONCLUSION: The sensitivity of mNGS was superior to that of Bactec MGIT 960; the specificity in NTMPD diagnosis was similar. mNGS shows effective performance in NTMPD diagnosis.

The diagnostic performance of endobronchial ultrasound with Xpert MTB/RIF Ultra in smear-negative pulmonary tuberculosis.

OBJECTIVE: This study investigated the diagnostic performance of endobronchial ultrasound with Xpert MTB/RIF Ultra (Ultra) for detecting smear-negative pulmonary tuberculosis (TB). METHODS: 143 patients suspected of sputum smear-negative pulmonary tuberculosis were enrolled in this study in Shanghai Pulmonary Hospital, China. These patients underwent endobronchial ultrasound with a guide sheath (EBUS-GS) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) based on their chest CT manifestations. We assessed the sensitivity and specificity of tissue specimens with Ultra in the TB group and non-TB group. Culture and clinical diagnosis were used as gold-standard for TB. RESULTS: Among these 143 patients, 11 patients were culture-positive TB, 85 patients were diagnosed with culture-negative TB and 47 were with the non-TB diseases. Direct testing with microscopy (Acid-Fast Bacilli smear, AFB), liquid culture, pathology, Xpert MTB/RIF(Xpert) test and Ultra had a sensitivity of 8.3%, 11.5%, 42.7%, 64.6%, and 78.1% individually among all the TB patients. Ultra had a higher sensitivity than Xpert (P = 0.011). But Ultra had a specificity of 59.6% (95% CI 44.3-73.3), lower than that of Xpert (89.4%, 95% CI 76.1-96.0, P = 0.001). Ultra had the same sensitivity on specimens from EBUS-TBNA and EBUS-GS (P = 0.975). Ultra's positive predictive value and negative predictive value were 79.8% and 57.1% respectively. CONCLUSIONS: Tissue specimens from interventional bronchoscopy combined with Ultra provide a sensitive method for diagnosing smear-negative pulmonary tuberculosis, but its specificity was lower than Xpert.

Deep vein thrombosis in a patient with Cronkhite-Canada syndrome: a complex case report.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare disease characterized by generalized gastrointestinal polyps, ectodermal abnormalities and variable gastrointestinal symptoms. Few cases to date have described complications with deep vein thrombosis (DVT). Here we reported a rare case of CCS concomitant with DVT. The patient's clinical details, endoscopic findings, safety, and efficacy are reported. CASE PRESENTATION: A 58-year-old patient was admitted to our hospital with recurrent diarrhea, overall abnormal appearance, including hyperpigmentation, hair loss and onychodystrophy, and multiple polyps distributed along the gastrointestinal tract except the esophagus. After considerable assessment, the patient was diagnosed with CCS. She was also diagnosed with concurrent DVT, nephrotic syndrome, and infectious enteritis during the course of disease. After treatment with a combination of methylprednisolone, mesalazine, antibiotics, rivaroxaban, and nutritional support during the 24 months of following the patient in this case, the clinical manifestations and endoscopic findings reached complete remission two years after the diagnosis. CONCLUSION: To our knowledge, this study is the first case of CCS complicated with DVT reported in China. Although rare, it is important to consider that DVT may occur after CCS and that it is vital to conduct careful follow-up.

Alveolar epithelial cell growth hormone releasing hormone receptor in alveolar epithelial inflammation.

Purpose: Growth hormone-releasing hormone (GHRH) is a 44-amino acid peptide that regulates growth hormone (GH) secretion. We hypothesized that GHRH receptor (GHRH-R) in alveolar type 2 (AT2) cells could modulate pro-inflammatory and possibly subsequent pro-fibrotic effects of lipopolysaccharide (LPS) or cytokines, such that AT2 cells could participate in lung inflammation and fibrosis. Methods: We used human alveolar type 2 (iAT2) epithelial cells derived from induced pluripotent stem cells (iPSC) to investigate how GHRH-R modulates gene and protein expression. We tested iAT2 cells' gene expression in response to LPS or cytokines, seeking whether these mechanisms caused endogenous production of pro-inflammatory molecules or mesenchymal markers. Quantitative real-time PCR (RT-PCR) and Western blotting were used to investigate differential expression of epithelial and mesenchymal markers. Result: Incubation of iAT2 cells with LPS increased expression of IL1-ß and TNF-α in addition to mesenchymal genes, including ACTA2, FN1 and COL1A1. Alveolar epithelial cell gene expression due to LPS was significantly inhibited by GHRH-R peptide antagonist MIA-602. Incubation of iAT2 cells with cytokines like those in fibrotic lungs similarly increased expression of genes for IL1-ß, TNF-α, TGFß-1, Wnt5a, smooth muscle actin, fibronectin and collagen. Expression of mesenchymal proteins, such as N-cadherin and vimentin, were also elevated after prolonged exposure to cytokines, confirming epithelial production of pro-inflammatory molecules as an important mechanism that might lead to subsequent fibrosis. Conclusion: iAT2 cells clearly expressed the GHRH-R. Exposure to LPS or cytokines increased iAT2 cell production of pro-inflammatory factors. GHRH-R antagonist MIA-602 inhibited pro-inflammatory gene expression, implicating iAT2 cell GHRH-R signaling in lung inflammation and potentially in fibrosis.

Effectiveness and safety of regimens containing linezolid for treatment of Mycobacterium abscessus pulmonary Disease.

OBJECTIVE: To evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease. METHODS: The records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups. RESULTS: The two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0-17.0] vs. 18.0 months [IQR: 16.0-18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01). CONCLUSIONS: The linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy.

The diagnosis interval influences risk factors of mortality in patients with co-existent active tuberculosis and lung cancer: a retrospective study.

BACKGROUND: Previous studies reported that tuberculosis (TB) is associated with an increased risk of lung cancer or the survival and mortality of lung cancer. However, the impact of coexisting TB on the survival of lung cancer patients was controversial. We aimed to identify risk factors on the survival rate of patients with co-existent active TB and lung cancer. METHODS: One hundred seventy-three patients diagnosed with active TB and lung cancer from January 2016 to August 2021 in Shanghai pulmonary hospital were selected and divided into two groups (≤ 6 months, > 6 months) according to the diagnosis interval between active TB and lung cancer (the order of diagnosis is not considered). The clinical characteristics and survival were analyzed. Univariate and multivariate logistic regression analyses were used to identify the risk factors for overall survival (OS). RESULTS: One hundred seventy-three patients were diagnosed with lung cancer and active TB. The study population exhibited a median age of 64 years, with a majority of 81.5% being male, 58.0% of patients had a history of smoking. Among those involved, 93.6% had pulmonary TB, 91.9% were diagnosed with non-small cell lung cancer (NSCLC), 76.9% were Eastern Cooperative Oncology Group (ECOG) 0-2 and 12.7% were ECOG 3-4. We observed better survival in the > 6 months group compared with the ≤ 6 months group (hazard ratio [HR] 0.456, 95% confidence interval [CI]:0.234-0.889, P = 0.017). The 1-, 3-, and 5- year OS rates were 94.2%, 80.3%, and 77.6%, respectively, in the > 6 months group and 88.3%, 63.8%, and 58.5%, respectively, in the ≤ 6 months group. Surgery (HR 0.193, [95% CI, 0.038-0.097]; P = 0.046) and ECOG Performance Status (HR 12.866, [95% CI, 2.730-60.638]; P = 0.001) were independent prognostic factors in the > 6 months group. CONCLUSIONS: Patients diagnosed with lung cancer and active TB for more than half a year have a significantly better prognosis than those diagnosed within half a year. ECOG Performance Status and surgery might possibly affect the outcomes of patients with co-existent active TB and lung cancer.

Correlation between Water Environment and Prevalence of Nontuberculous Mycobacteria Pulmonary Disease: A Case-Control Study.

Objective: Nontuberculous mycobacteria (NTM) prevalence in water systems has raised concerns about Nontuberculous Mycobacteria Pulmonary Disease (NTM-PD). Understanding the relationship between NTM-PD, drinking water distribution systems (DWDS), and other epidemiological factors is crucial for public health. Methods: A case-control study was conducted at the Inpatient Department of Tuberculosis Department of Shanghai Pulmonary Hospital. Subjects were divided into the NTM-PD group (n = 314) and pulmonary tuberculosis (PTB) group (n = 308) at a 1:1 ratio. Data was collected through questionnaires covering general information, depression (Self-Rating Depression Scale, SDS), and anxiety (Self-Rating Anxiety Scale, SAS). Multivariate unconditional logistic regression analysis was employed for the study. Results: The average age of NTM-PD patients was 55.26±14.44, with clinical symptoms including chest tightness, shortness of breath, hemoptysis, fever, and expectoration. Risk factors for NTM-PD included age (>60 years old, OR=1.042), gender (female, OR = 3.089), secondary water supply system (OR = 7.813), occupation (farmer/flower farmer, OR=2.676), depression (OR = 2.956), recurrent bronchiectasis (OR = 6.314), chronic obstructive pulmonary disease (COPD, OR = 2.704), and autoimmune disease (OR = 13.588) (P < .05). Use of household water purifiers was identified as a protective factor (OR = 0.128, P < .001). Conclusion: DWDS, drinking water mode, soil-related occupation, bronchiectasis, COPD, age, sex, and depression were closely related to the risk of NTM-PD. It is suggested to pay attention to water hygiene and illness progress and regulate mood to prevent NTM-PD in daily life.