The interferon-induced protein, IFIT2, requires RNA-binding activity and neuronal expression to protect mice from intranasal vesicular stomatitis virus infection.

The interferon (IFN) system protects mammals from diseases caused by virus infections. IFN synthesis is induced by pattern recognition receptor signaling pathways activated by virus infection. IFN is secreted from the infected cells and acts upon neighboring cells by binding cell surface receptors and triggering induction of hundreds of IFN-stimulated genes and proteins, many of which block different steps of virus replication. The IFN-induced tetratricopeptide repeat proteins (IFIT) are a family of RNA-binding proteins. We and others have previously reported that IFIT2 protects mice from many neurotropic RNA viruses; indeed, Ifit2-/- mice are very susceptible to intranasal or subcutaneous infections with vesicular stomatitis virus (VSV). Here, using a newly generated conditional knockout mouse, we report that ablation of Ifit2 expression only in neuronal cells was sufficient to render mice susceptible to neuropathogenesis caused by intranasal, but not subcutaneous, infection of VSV. Another genetically modified mouse line, expressing a mutant IFIT2 that cannot bind RNA, was as susceptible to VSV infection as Ifit2-/- mice. These results demonstrated that IFIT2 RNA-binding activity is essential for protecting mice against neurological diseases caused by intranasal infection of VSV.IMPORTANCEInterferon's (IFN's) antiviral effects are mediated by the proteins encoded by the interferon-stimulated genes. IFN-stimulated genes (IFIT2) is one such protein, which inhibits replication of many RNA viruses in the mouse brain and the resultant neuropathology. Our study sheds light on how IFIT2 works. By ablating Ifit2 expression only in neuronal cells, using a newly generated conditional knockout mouse line, we showed that Ifit2 induction in the neurons of the infected mouse was necessary for antiviral function of interferon. IFIT2 has no known enzyme activity; instead, it functions by binding to cellular or viral proteins or RNAs. We engineered a new mouse line that expressed a mutant IFIT2 that cannot bind RNA. These mice were very susceptible to infection with vesicular stomatitis virus indicating that the RNA-binding property of IFIT2 was essential for its antiviral function in vivo.

A novel transcranial MR Guided focused ultrasound method based on the ultrashort echo time skull acoustic model and phase retrieval techniques.

Transcranial ultrasound stimulation (TUS) has been clinically applied as a neuromodulation tool. Particularly, the phase array ultrasound can be applied in TUS to non-invasively focus on the cortex or deep brain. However, the vital phase distortion of the ultrasound induced by the skull limits its clinical application. In the current study, we aimed to develop a hybrid method that combines the ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences with the prDeep technique to achieve focusing ventral intermediate thalamic nucleus (VIM). The time-reversal (TR) approach of the UTE numerical acoustic model of the skull combined with the prDeep algorithm was used to reduce the number of iterations. The skull acoustic model simulation therapy process was establish to valid this method's prediction and focus performance, and the classical TR method were considered as the gold standard (GS). Our approach could restore 75% of the GS intensity in 25 iteration steps, with a superior the noise immunity. Our findings demonstrate that the phase aberration caused by the skull can be estimated using phase retrieval techniques to achieve a fast and accurate transcranial focus. The method has excellent adaptability and anti-noise capacity for satisfying complex and changeable scenarios.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of ß-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Successful rescue of disseminated Nocardia infection with multiple abscesses in a patient with membranous nephropathy after cardiopulmonary resuscitation: A three-year follow-up.

Nocardiosis manifests as an opportunistic infection, primarily affecting individuals who are immunocompromised and susceptible to the infection. We present a case study of one patient with nephrotic syndrome and membranous nephropathy, who underwent treatment with prednisone and cyclosporine in 2016. In early 2017, the patient was diagnosed with a "fungal infection" and discontinued the use of cyclosporine. After one month of anti-infection therapy, a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region. The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses, multiple lung and brain lesions, and a positive culture of Nocardia in the drainage. We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and voriconazole. However, the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation. During the five-month follow-up period following the discharge, the patient displayed an enhanced nutritional status and stable renal function. The focal infection ultimately resolved during the subsequent three years. Neuro-infection caused by Nocardia should be considered in immunocompromised patients, and TMP-SMX is the preferred initial therapy; however, because of the high mortality rate, a long-term combination therapy with imipenem, cefotaxime, amikacin, and TMP-SMX is suggested.

Inflammatory Cytokines Can Induce Synthesis Of Type-I Interferon.

Type I interferon (IFN) is induced in virus infected cells, secreted and it inhibits viral replication in neighboring cells. IFN is also an important player in many non-viral diseases and in the development of normal immune cells. Although the signaling pathways for IFN induction by viral RNA or DNA have been extensively studied, its mode of induction in uninfected cells remains obscure. Here, we report that inflammatory cytokines, such as TNF-α and IL-1ß, can induce IFN-ß through activation of the cytoplasmic RIG-I signaling pathway. However, RIG-I is activated not by RNA, but by PACT, the protein activator of PKR. In cell lines or primary cells expressing RIG-I and PACT, activation of the MAPK, p38, by cytokine signaling, leads to phosphorylation of PACT, which binds to primed RIG-I and activates its signaling pathway. Thus, a new mode of type I IFN induction by ubiquitous inflammatory cytokines has been revealed. Key points: Cytochalasin D followed by TNF-α / IL-1ß treatment activates IFN-ß expression.IFN-ß expression happens due to activation of RIG-I signaling.Interaction between RIG-I and PACT activates IFN-ß expression.

Association between chemotherapy-induced myelosuppression and curative efficacy of 2-cycle chemotherapy in small cell lung cancer.

BACKGROUND: The association of chemotherapy-induced myelosuppression with tumor response and overall survival remained controversial. The study was conducted to investigate the association between them in small cell lung cancer (SCLC). METHODS: 204 eligible patients with SCLC were respectively included and categorized into three groups (no, mild, and severe myelosuppression) based on myelosuppression degree after the first chemotherapy. Curative efficacy of 2-cycle chemotherapy was evaluated by the objective response rate (ORR) and disease control rate (DCR). Univariate and multivariate logistic regression analyses were conducted to investigate their association. Receiver operator characteristic (ROC) curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to assess the predictive ability of myelosuppression. RESULTS: In the fully-adjusted model, mild (OR, 4.61; 95% CI, 1.35 to 18.27; P = 0.020) and severe (OR, 7.22; 95% CI, 1.30 to 72.44; P = 0.046) myelosuppression were positively associated with DCR. However, only mild myelosuppression was significantly associated with ORR (OR, 2.78; 95% CI, 1.30 to 6.14; P = 0.010). Although we observed evidence of increased ORR in severe myelosuppression, the difference was not statistically significant. Furthermore, based on the results of the ROC curve, NRI and IDI, chemotherapy-induced myelosuppression cannot be used as a accurate and independent predictor for curative efficacy, but it can improve overall prediction accuracy. CONCLUSION: Chemotherapy-induced myelosuppression was significantly associated with curative efficacy of 2-cycle chemotherapy in SCLC, which could help predict treatment efficacy and guide chemotherapy dosage.

Dynamic changes of fecal microbiota in a weight-change model of Bama minipigs.

Introduction: Obesity is closely related to gut microbiota, however, the dynamic change of microbial diversity and composition during the occurrence and development process of obesity is not clear. Methods: A weight-change model of adult Bama pig (2 years, 58 individuals) was established, and weight gain (27 weeks) and weight loss (9 weeks) treatments were implemented. The diversity and community structures of fecal microbiota (418 samples) was investigated by using 16S rRNA (V3-V4) high-throughput sequencing. Results: During the weight gain period (1~27 week), the alpha diversity of fecal microbiota exhibited a "down-up-down" fluctuations, initially decreasing, recovering in the mid-term, and decreasing again in the later stage. Beta diversity also significantly changed over time, indicating a gradual deviation of the microbiota composition from the initial time point. Bacteroides, Clostridium sensu stricto 1, and Escherichia-Shigella showed positive correlations with weight gain, while Streptococcus, Oscillospira, and Prevotellaceae UCG-001 exhibited negative correlations. In the weight loss period (30~38 week), the alpha diversity further decreased, and the composition structure underwent significant changes compared to the weight gain period. Christensenellaceae R-7 group demonstrated a significant increase during weight loss and showed a negative correlation with body weight. Porphyromonas and Campylobacter were positively correlated with weight loss. Discussion: Both long-term fattening and weight loss induced by starvation led to substantial alterations in porcine gut microbiota, and the microbiota changes observed during weight gain could not be recovered during weight loss. This work provides valuable resources for both obesity-related research of human and microbiota of pigs.

Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer.

ß-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods are mainly achieved by amino(hetero)arylation reaction with the aid of transition metals and preactivated substrates. Herein, we report a metal-free and photoinduced intermolecular amino(hetero)arylation reaction for the single-step installation of both (hetero)aryl and iminyl groups across alkenes in an efficient and regioselective manner. This method shows broad scope (up to 124 examples) and excellent tolerance of various olefins─from the simplest ethylene to complex multisubstituted alkenes can all participate in the reaction. Furthermore, aminosulfonylation of alkenes can be also conducted in the presence of sodium bisulfite as the SO2 source.

Frailty in asthma-COPD overlap: a cross-sectional study of association and risk factors in the NHANES database.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterised by the simultaneous presence of features of both asthma and COPD. The study aims to investigate the association between ACO and frailty among middle-aged and elderly populations, and identify the risk factors for frailty in individuals with ACO. METHODS: We conducted a cross-sectional study with 34 403 eligible participants (aged ≥40 years) from the National Health and Nutrition Examination Survey 1999-2018 cycles. Participants were stratified into four groups: ACO, asthma, COPD and non-asthma/COPD. Frailty assessment was based on frailty index, generating frail and non-frail group. Univariate and multivariate survey-weighted logistic regression analysis were used to determine the association between ACO and frailty, and to identify the risk factors for frailty in ACO. RESULTS: The frailty prevalence in participants with ACO was 60.2%, significantly higher than that in those with asthma (32.3%) and COPD (40.6%). In the unadjusted model, participants with ACO exhibited six-fold higher odds of frailty (OR 6.30, 95% CI 5.29 to 7.49), which was significantly greater than those with COPD (OR 2.84, 95% CI 2.46 to 3.28) and asthma (OR 1.99, 95% CI 1.80 to 2.18), using the non-asthma/COPD group as a reference. After adjusting for all confounders, participants with ACO had over four times higher odds of frailty (OR 4.48, 95% CI 3.53 to 5.71), still higher than those with asthma and COPD. The findings remained robust in sensitivity and subgroup analyses. Furthermore, hypertension, cancer, cardiovascular disease, chronic kidney disease and cognitive disorders were identified as risk factors for frailty among ACO participants, while higher income and education levels were protective factors. CONCLUSION: Patients (aged ≥40 years) with ACO were at a higher risk of frailty, regardless of age or sex, compared with those with asthma or COPD alone. Greater attention should be paid to patients with ACO, regardless of their age.

Loss of circIGF1R Suppresses Cardiomyocytes Proliferation by Sponging miR-362-5p.

Circular RNAs (circRNAs) are generally formed by the back-splicing of precursor mRNA. Increasing evidence implicates the important role of circRNAs in cardiovascular diseases. However, the role of circ-insulin-like growth factor 1 receptor (circIGF1R) in cardiomyocyte (CM) proliferation remains unclear. Here, we investigated the potential role of the circIGF1R in the proliferation of CMs. We found that circIGF1R expression in heart tissues and primary CMs from adult mice was significantly lower than that in neonatal mice at postnatal 1 day (p1). Increased circIGF1R expression was detected in the injured neonatal heart at 0.5 and 1 days post-resection. circIGF1R knockdown significantly decreased the proliferation of primary CMs. Combined prediction software, luciferase reporter gene analysis, and quantitative real time-PCR (qPCR) revealed that circIGF1R interacted with miR-362-5p. A significant increase in miR-362-5p expression was detected in the adult heart compared with that in the neonatal heart. Further, heart injury significantly decreased the expression of miR-362-5p in neonatal mice. Treatment with miR-362-5p mimics significantly suppressed the proliferation of primary CMs, whereas knockdown of miR-362-5p promoted the CMs proliferation. Meanwhile, miR-362-5p silencing can rescue the proliferation inhibition of CMs induced by circIGF1R knockdown. Target prediction and qPCR validation revealed that miR-362-5p significantly inhibited the expression of Phf3 in primary CMs. In addition, decreased Phf3 expression was detected in adult hearts compared with neonatal hearts. Consistently, increased Phf3 expression was detected in injured neonatal hearts compared with that in sham hearts. Knockdown of Phf3 markedly repressed CMs proliferation. Taken together, these findings suggest that circIGF1R might contribute to cardiomyocyte proliferation by promoting Pfh3 expression by sponging miR-362-5p and provide an important experimental basis for the regulation of heart regeneration.

SPatiotemporal-ENcoded acoustic radiation force imaging of focused ultrasound.

Neuromodulation technology has provided novel therapeutic approaches for diseases caused by neural circuit dysfunction. Transcranial focused ultrasound (FU) is an emerging neuromodulation approach that combines noninvasiveness with relatively sharp focus, even in deep brain regions. It has numerous advantages such as high precision and good safety in neuromodulation, allowing for modulation of both peripheral and central nervous systems. To ensure accurate treatment targeting in FU neuromodulation, a magnetic resonance acoustic radiation force imaging (MR-ARFI) sequence is crucial for the visualization of the focal point. Currently, the commonly used 2D Spin Echo ARFI (2D SE-ARFI) sequence suffers from the long acquisition time, while the echo planar imaging ARFI (EPI-ARFI) sequence with a shorter acquisition time is vulnerable to the magnetic field inhomogeneities. To address these problems, we proposed a spatiotemporal-encoded acoustic radiation force imaging sequence (i.e., SE-SPEN-ARFI, shortened to SPEN-ARFI) in this study. The displacement at the focal spot obtained was highly consistent with that of the SE-ARFI sequence. Our research shows that SPEN-ARFI allows for rapid image acquisition and has less image distortions even under great field inhomogeneities. Therefore, a SPEN-ARFI sequence is a practical alternative for the treatment planning in ultrasound neuromodulation.

Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is a pathophysiological state of abnormally elevated pulmonary arterial pressure caused by drugs, inflammation, toxins, viruses, hypoxia, and other risk factors. We studied the therapeutic effect and target of tetramethylpyrazine (tetramethylpyrazine [TMP]; ligustrazine) in the treatment of PAH and we speculated that dramatic changes in myocardin levels can significantly affect the progression of PAH. In vivo, the results showed that administration of TMP significantly prolonged the survival of PAH rats by reducing the proliferative lesions, right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and the Fulton index in the heart and lung of PAH rats. In vitro, TMP can regulate the levels of smooth muscle protein 22-alpha (SM22-α), and myocardin as well as intracellular cytokines such as NO, transforming growth factor beta (TGF-ß), and connective tissue growth factor (CTGF) in a dose-dependent manner (25, 50, or 100 µM). Transfection of myocardin small interfering RNA (siRNA) aggravated the proliferation of pulmonary artery smooth muscle cells (PSMCs), and the regulatory effect of TMP on α-smooth muscle actin (α-SMA) and osteopontin (OPN) disappeared. The application of 10 nM estrogen receptor alpha (ERα) inhibitor MPP promoted the proliferation of PSMCs, but it does not affect the inhibition of TMP on PSMCs proliferation. Finally, we found that TMP promoted the nucleation of myocardin-related transcription factor-A (MRTF-A) and combined it with myocardin. In conclusion, TMP can inhibit the transformation of PSMCs from the contractile phenotype to the proliferative phenotype by promoting the formation of the nuclear (MRTF-A/myocardin) transcription complex to treat PAH.

Association of weight range with telomere length: A retrospective cohort study.

Objective: Previous research has shown a significant association between weight and telomere length, but did not take into consideration weight range. The study was to investigate the association of weight range with telomere length. Methods: Data of 2918 eligible participants aged 25-84 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cycle were analyzed. Information about demographic variables, lifestyle factors, anthropometric variables, and medical comorbidities were included. Univariate and multivariate linear regression model with adjustments for potential confounders were employed to determine the association between weight range and telomere length. A non-parametrically restricted cubic spline model was used to illustrate the possible non-linear relationship. Results: In univariate linear regression, BMImax, BMI range, and weight range all revealed significant negative associations with telomere length. However, annual rate of BMI/weight range showed a significant positive associations with telomere length. There was no significant association between telomere length and BMImin. After adjusting for potential confounders, the inverse associations persisted in BMImax (ß=-0.003, P<0.001), BMI range (ß=-0.002, P=0.003), and weight range (ß=-0.001, P=0.001). Furthermore, annual rate of BMI range (ß=-0.026, P=0.009) and weight range (ß=-0.010, P=0.007) presented negative associations with telomere length, after adjusting for covariates in Model 2-4. The association between BMImin (ß =-0.002, P=0.237) and telomere length still could not reach statistical significance in multivariate linear regression model. The results of restricted cubic spline analysis showed that BMImax (P for nonlinear =0.026), BMI range (P for nonlinear =0.022), weight range (P for nonlinear =0.035), annual rate of BMI range (P for nonlinear =0.030), and annual rate of weight range (P for nonlinear =0.027) all had nonlinear inverse associations with telomere length. Conclusions: The study suggests that weight range is inversely associated with telomere length in U.S. adults. Larger weight fluctuation may accelerate telomere shortening and aging.

Inhibition of mitochondrial phosphate carrier prevents high phosphate-induced superoxide generation and vascular calcification.

Vascular calcification is a serious complication of hyperphosphatemia that causes cardiovascular morbidity and mortality. Previous studies have reported that plasmalemmal phosphate (Pi) transporters, such as PiT-1/2, mediate depolarization, Ca2+ influx, oxidative stress, and calcific changes in vascular smooth muscle cells (VSMCs). However, the pathogenic mechanism of mitochondrial Pi uptake in vascular calcification associated with hyperphosphatemia has not been elucidated. We demonstrated that the phosphate carrier (PiC) is the dominant mitochondrial Pi transporter responsible for high Pi-induced superoxide generation, osteogenic gene upregulation, and calcific changes in primary VSMCs isolated from rat aortas. Notably, acute incubation with high Pi markedly increased the protein abundance of PiC via ERK1/2- and mTOR-dependent translational upregulation. Genetic suppression of PiC prevented Pi-induced ERK1/2 activation, superoxide production, osteogenic differentiation, and vascular calcification of VSMCs in vitro and aortic rings ex vivo. Pharmacological inhibition of mitochondrial Pi transport using butyl malonate (BMA) or mersalyl abolished all pathologic changes involved in high Pi-induced vascular calcification. BMA or mersalyl also effectively prevented osteogenic gene upregulation and calcification of aortas from 5/6 subtotal nephrectomized mice fed a high-Pi diet. Our results suggest that mitochondrial Pi uptake via PiC is a critical molecular mechanism mediating mitochondrial superoxide generation and pathogenic calcific changes, which could be a novel therapeutic target for treating vascular calcification associated with hyperphosphatemia.

Persistent response of furmonertinib plus anlotinib in a lung adenocarcinoma patient with an EGFR exon 20 insertion mutation: A case report.

Insertions in exon 20 represent the third most common type of EGFR mutation following in-frame deletions in exon 19 and the point mutation L858R in exon 21. They are generally associated with primary resistance to EGFR-TKIs. Although mobocertinib and amivantamab were approved for adult patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, the efficacy of these two agents was rather moderate. Therefore, other more potent targeted agents are urgently needed. Here, we report a patient with advanced lung adenocarcinoma harboring an EGFR exon 20 insertion mutation (NM_005228: exon 20: c.2316_2321dup: p.773_774dup). After experiencing platinum-based chemotherapy, this patient received a combination of furmonertinib and anlotinib and achieved lasting stable disease (SD). The treatment was well tolerated, and only mild hand-foot syndrome was reported from the patient. To the best of our knowledge, this case firstly reported the encouraging efficacy of combined furmonertinib and anlotinib in an advanced lung adenocarcinoma patient with an EGFR exon 20 insertion mutation who was previously treated with platinum-based chemotherapy. In addition, we summarize the recent literature on therapies against NSCLC with EGFR exon 20 insertion mutations. This case might provide an alternative approach for clinical oncologists.

Associations of adherence to the DASH diet and the Mediterranean diet with chronic obstructive pulmonary disease among US adults.

Background: The Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet are associated with reduced cardiovascular, tumor, and diabetes risk, but the effect on chronic obstructive pulmonary disease (COPD) is uncertain. Objective: To investigate the association of the DASH diet and the Mediterranean diet with the risk of COPD in American adults. Methods: This cross-sectional study included 28,605 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 survey cycle who had complete dietary and other questionnaire data. The scores of healthy eating patterns (the DASH diet and the Mediterranean diet) were derived from a 24-h dietary recall interview [individual food and total nutrient data from NHANES and food pattern equivalents data from the United States Department of Agriculture (USDA)]. The primary outcome was the prevalence of COPD. COPD was defined based on participants self-reported whether or not a doctor or health professional had diagnosed chronic bronchitis or emphysema. Secondary outcomes were lung function and respiratory symptoms. All analyses were adjusted for demographics and standard COPD risk factors (primary tobacco exposure, secondhand smoke exposure, and asthma). Results: This study included 2,488 COPD participants and 25,607 non-COPD participants. We found that a higher DASH diet score was associated with a lower risk of COPD [odds ratio (OR): 0.83; 95% confidence interval (CI): 0.71-0.97; P = 0.021]. This association persisted in several subgroups [men (OR: 0.73; 95% CI: 0.58-0.93; P = 0.010), relatively young (OR: 0.74; 95% CI: 0.55-1.01; P = 0.050), and smoker (OR: 0.82; 95% CI: 0.67-0.99; P = 0.038)]. In contrast, the Mediterranean diet score was not significantly associated with COPD prevalence in this large cross-sectional analysis representative of the US adult population (OR: 1.03; 95% CI: 0.88-1.20; P = 0.697). In addition, we found a correlation between DASH diet adherence and lung function [ß: -0.01; 95% CI: -0.01-0.00; P = 0.003 (FEV1: FVC)] or respiratory symptoms [OR: 0.80; 95% CI: 0.73-0.89; P < 0.001 (dyspnea); OR: 0.80; 95% CI: 0.70-0.91; P = 0.002 (cough); OR: 0.86; 95% CI: 0.74-0.99; P = 0.042 (expectoration)], especially in non-COPD populations. Conclusion: A higher DASH diet score was associated with improved COPD prevalence, lung function and respiratory symptoms. This new finding supports the importance of diet in the pathogenesis of COPD and expands the scope of the association of the DASH diet score with major chronic diseases.

Effect of regional intrinsic activity following two kinds of theta burst stimulation on precuneus.

Theta burst stimulation (TBS) has been widely used in the treatment of mental disorders, but the cerebral functional difference between intermittent TBS (iTBS) and continuous TBS (cTBS) after one single session of stimulation is not clear. Here we applied resting-state functional magnetic resonance imaging (RS-FMRI) to evaluate the alterations in intrinsic brain activity after iTBS and cTBS in the precuneus. We recruited 32 healthy young adults and performed a single session each of iTBS and cTBS at a 1-week interval. RS-fMRI was collected at baseline before and immediately after the stimulation. Parameters for regional brain activity (ALFF/fALFF/ReHo) and functional connectivity (FC) with the stimulated site of the precuneus after iTBS and cTBS were calculated and compared between each stimulation using a paired t-test. Correlation analysis among those parameters was calculated to explore whether changes in functional connectivity were associated with local spontaneous activity. After iTBS stimulation, fALFF increased in the bilateral precuneus, while fALFF decreased in the bilateral middle temporal gyrus. Reductions in precuneus FC were found in the bilateral cuneus, superior occipital gyrus, superior temporal gyrus, precentral gyrus, and postcentral gyrus, which correlated with regional activity. After cTBS, fALFF decreased in the bilateral insula, and precuneus FC was decreased in the bilateral inferior occipital gyrus and increased in the thalamus. In the current study, we observed that one session of iTBS or cTBS could cause inhibitory effects in remote brain regions, but only iTBS caused significant local activation in the target region.