Relationship between coronary microvascular dysfunction (CMD) and left ventricular diastolic function in patients with symptoms of myocardial ischemia with non-obstructive coronary artery disease (INOCA) by cardiovascular magnetic resonance feature-tracking.

AIM: To investigate whether there was an association between coronary microvascular dysfunction (CMD) and left ventricular (LV) diastolic function in patients with myocardial ischemia with non-obstructive coronary artery disease (INOCA). MATERIALS AND METHODS: Our study included 115 subjects with suspected myocardial ischemia that underwent stress perfusion cardiac magnetic resonance (CMR). They were divided into non-CMD and CMD two groups. CMR-derived volume-time curves and CMR-FT parameters were used to assess LV diastolic function using CVI42 software. The latter included global/regional LV peak longitudinal, circumferential, radial diastolic strain rate (LDSR, CDSR, RDSR). Logistic regression analysis was performed with CMR-FT strain parameters as independent variables and CMD as dependent variables, and the effect value was expressed as an odds ratio (OR). RESULTS: Of the 115 patients, we excluded data from 23 patients and 92 patients (56.5% male；52 ± 12 years) were finally included in the study. Of these, 19 patients were included in the non-CMD group (49 ± 11 years) and CMD group included 73patient (52 ± 12 years). The regional CDSR (P=0.019), and regional RDSR (P=0.006) were significantly lower in the CMD group than in non-CMD group. But, regional LDSR in CMD group was higher than non-CMD (P=0.003). In logistic regression analysis, regional LDSR (adjusted ß= 0.1, 95%CI 0.077, 0.349, p=0.002) and RDSR (adjusted ß= 0.1, 95 % CI 0.066, 0.356, p=0.004) were related to CMD. CONCLUSIONS: LV myocardial perfusion parameter MPRI was negatively correlated with LV diastolic function (CDSR) which needs to take into account the degree of diastolic dysfunction.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia.

AIM: To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. MATERIALS AND METHODS: The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). RESULTS: Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53 ± 12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. CONCLUSION: The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Adenosine triphosphate (ATP): a safe and effective vasodilator for stress perfusion cardiac magnetic resonance imaging.

AIM: To evaluate the efficiency and safety of adenosine triphosphate (ATP) as a stress agent in a cohort of patients undergoing stress perfusion cardiac magnetic resonance imaging (CMRI). MATERIALS AND METHODS: This retrospective study was conducted between December 2019 and October 2021. The study recruited patients who underwent stress perfusion CMRI using ATP as a vasodilator. Adverse events, such as chest pain, flushing, dyspnoea, headache, and splenic switch-off (SSO) phenomenon, were evaluated in the patients who underwent stress perfusion CMRI. RESULTS: The study included 107 patients (age range: 53 ± 11 years; male:female, 62%:38%). The haemodynamic response (heart rate increased by ≥ 10 beats/min) was quick and observed within 2 minutes of ATP infusion. Scanning was stopped in three patients because of atrioventricular block. CMRI images of seven out of 104 patients were excluded from the final analysis because of inferior quality. During ATP infusion, 37/107 patients (35%) experienced mild adverse events, such as chest pain, flushing, dyspnoea, headache, and atrioventricular block. Myocardial infarction and bronchospasms were not observed during ATP infusion. SSO, a marker of adequate stress, was observed in 91% (94/103) of the patients who underwent stress perfusion CMRI. CONCLUSIONS: As a coronary vasodilator, ATP was safe for stress perfusion CMRI. In addition, the adverse events during ATP infusion were mild, which were relieved within 2 minutes of ATP injection cessation. SSO could serve as an indicator of stress success in ATP stress perfusion CMRI.

Deep-learning model associating lateral cervical radiographic features with Cormack-Lehane grade 3 or 4 glottic view.

Unanticipated difficult laryngoscopy is associated with serious airway-related complications. We aimed to develop and test a convolutional neural network-based deep-learning model that uses lateral cervical spine radiographs to predict Cormack-Lehane grade 3 or 4 direct laryngoscopy views of the glottis. We analysed the radiographs of 5939 thyroid surgery patients at our hospital, 253 (4%) of whom had grade 3 or 4 glottic views. We used 10 randomly sampled datasets to train a model. We compared the new model with six similar models (VGG, ResNet, Xception, ResNext, DenseNet and SENet). The Brier score (95%CI) of the new model, 0.023 (0.021-0.025), was lower ('better') than the other models: VGG, 0.034 (0.034-0.035); ResNet, 0.033 (0.033-0.035); Xception, 0.032 (0.031-0.033); ResNext, 0.033 (0.032-0.033); DenseNet, 0.030 (0.029-0.032); SENet, 0.031 (0.029-0.032), all p < 0.001. We calculated mean (95%CI) of the new model for: R2 , 0.428 (0.388-0.468); mean squared error, 0.023 (0.021-0.025); mean absolute error, 0.048 (0.046-0.049); balanced accuracy, 0.713 (0.684-0.742); and area under the receiver operating characteristic curve, 0.965 (0.962-0.969). Radiographic features around the hyoid bone, pharynx and cervical spine were associated with grade 3 and 4 glottic views.

[Effects of macrophage glycolytic reprogramming on tuberculosis granuloma formation].

The formation of granulomatous lesions is a typical pathological feature of tuberculosis, and infection with Mycobacterium tuberculosis is the main cause. Although the mechanism underlying granuloma formation remains unclear, increasing evidence suggests that immune metabolism plays an important role. In this review, we summarized the latest advances in macrophage glycolytic reprogramming in tuberculosis granuloma formation to discover new methods for early diagnosis and provided new ideas for tuberculosis therapeutics based on the regulation of immune metabolism.

[Progress in clinical diagnosis and treatment of multiple primary lung cancer].

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

[Influence of female age on the fresh cycle live birth rate of different controlled ovarian hyperstimulation protocols in poor ovarian response patients].

Objective: To investigate the influence of age on the fresh cycle live birth rate in patients with poor ovarian response in different controlled ovarian hyperstimulation groups. Methods: The clinical data of 3 342 patients in The First Affiliated Hospital of Zhengzhou University from February 2014 to November 2018 were retrospectively collected, including early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol group (1 375 cases), mid-luteal phase short-acting GnRH agonist long protocol group (1 161 cases) and GnRH antagonist protocol group (806 cases); each group was divided into 4 subgroups according to age: ≤30 years, 31－35 years, 36－40 years and >40 years, the pregnancy outcomes in each age subgroup were analyzed under different controlled ovarian hyperstimulation protocols. Results: In early-follicular phase long-acting GnRH agonist long protocol group, the final live birth rates of each age subgroup were 39.4% (228/579), 36.1% (135/374), 16.6% (48/290) and 3.0% (4/132); in mid-luteal phase short-acting GnRH agonist long protocol group, live birth rates of each age subgroup were 32.1% (99/308), 20.8% (55/264), 13.0% (45/346) and 7.0% (17/243); in GnRH antagonist protocol group, live birth rates of each age subgroup were 22.8% (26/114), 16.3% (25/153), 11.2% (31/278), and 3.8% (10/261); the live birth rate of each group decreased significantly with the increase of age (all P<0.01). When the age≤35 years old, the fresh cycle live birth rate of the early-follicular phase long-acting GnRH agonist long protocol group was significantly better than those of the other two groups (all P<0.01). The multivariate logistic regression analysis of age and live birth rate of the three controlled ovarian hyperstimulation groups showed age was the independent influence factor (OR=0.898, 95%CI: 0.873-0.916, P<0.01; OR=0.926, 95%CI: 0.890-0.996, P<0.01; OR=0.901, 95%CI: 0.863-0.960, P<0.01). Conclusions: Age is an independent influencing factor for the prediction of fresh cycle live birth rate in low ovarian response patients. No matter which controlled ovarian hyperstimulation protocol is adopted, the final live birth rate decreases significantly with the increase of women's age. In addition, the early-follicular phase long-acting GnRH agonist long protocol has the highest fresh cycle live birth rate among all controlled ovarian hyperstimulation groups.

[Analysis of clinical characteristics of 21 cases of acute fibrinous and organizing pneumonia].

Objective: To summarize the clinical features of 21 cases of acute fibrinous and organizing pneumonia (AFOP) confirmed by pathology, thereby improving clinicians' understanding of this disease and avoiding misdiagnosis in clinical practice. Methods: Twenty-one patients diagnosed pathologically with AFOP from January 2016 to April 2019 were analyzed retrospectively. The clinical symptoms, laboratory examination results, imaging features, treatments and outcomes were analyzed comprehensively. Results: There were 10 males and 11 females, with an average age of (58±10) years. All the cases presented subacute disease onset. The main symptoms were cough, expectoration and fever. The results from laboratory examination showed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than the normal levels. The total number of leukocytes, the percentage of neutrophils, and procalcitonin were also higher than the normal levels. Among these patients, 4 cases showed positive sputum bacteriology. Nine patients were found to have probable etiological factors (infections in 4, tumors in 4 cases, and connective tissue disease in 1 case). Twelve patients had no confirmed etiological factors. As to radiological findings, the patterns were multiple patchy infiltrates(16/21), solitary mass (3/21) and multiple nodules in both lungs (2/21). Most lesions were subpleural in distribution (15/21), with air bronchogram sign (11/21), pleural effusion (9/21), and cavity (4/21). Three patients received anti-infective therapy only. The infiltration in lung disappeared within 2 months in one patient, but the lesion still existed in one case after three years of follow-up. However, one patient were lost during the follow-up. Eighteen patients were treated with oral glucocorticoids, and about 50% of the patients showed significant improvement in symptoms and imaging findings within one month. The average follow-up time was (22±10) months, and there was no death. Conclusions: The clinical and imaging findings of AFOP are nonspecific. The exact mechanism of its pathogenesis is not clear. Infection and tumor may be related to the pathogenesis of AFOP. AFOP with subacute onset has a good response to glucocorticoid treatment with a better prognosis.

[Risk factors of postoperative complications after laparoscopic surgery for pheochromocytoma].

Objective: To investigate the effects of intraoperative hemodynamic instability on postoperative complications of laparoscopic surgery for pheochromocytoma. Methods: It was a retrospective cohort study. According to inclusion/exclusion criteria, adult patients underwent laparoscopic surgery for pheochromocytoma from January 2005 to December 2017 in Peking University First Hospital were enrolled in this study. Eligible patients were divided into two groups by evidence of postoperative complications to find out the effects of intraoperative hemodynamic instability and its' effects on other prognostic indices. The normally distributed continuous variables were compared between two groups by Student's t test, Mann-Whitney U test were used for the comparison for non-normally distributed continuous variables and χ(2) test for categorical variables. Results: A total of 198 patients were finally enrolled in this study, including 87 males and 111 females with an average age of (47±15) years. Postoperative complications occurred in 17 patients with an incidence of 8.6%, and intraoperative hemodynamic instability occurred in 45 patients (22.7%). It was found that history of stroke[odds ratio (OR)=13.387, 95% confidence interval (CI): 2.284-78.460, P=0.004], intraoperative hemodynamic instability (OR=3.351, 95%CI: 1.119-10.039, P=0.031) and intraoperative positive fluid balance (for each additional 100 ml) (OR=1.087, 95%CI: 1.031-1.146, P=0.002)were the independent risk factors of postoperative complications of laparoscopic surgery for pheochromocytoma. Furthermore, more postoperative complications, higher rate of admitting to ICU and longer hospital stay was found in patients with hemodynamic instability. Conclusion: Intraoperative hemodynamic instability is an independent risk factor for postoperative complications of laparoscopic surgery in patients with pheochromocytoma, and it associates with more postoperative complications and higher rate of admitting to ICU.

Genome re-sequencing to identify single nucleotide polymorphism markers for muscle color traits in broiler chickens.

OBJECTIVE: Meat quality including muscle color in chickens is an important trait and continuous selective pressures for fast growth and high yield have negatively impacted this trait. This study was conducted to investigate genetic variations responsible for regulating muscle color. METHODS: Whole genome re-sequencing analysis using Illumina HiSeq paired end read method was performed with pooled DNA samples isolated from two broiler chicken lines divergently selected for muscle color (high muscle color [HMC] and low muscle color [LMC]) along with their random bred control line (RAN). Sequencing read data was aligned to the chicken reference genome sequence for Red Jungle Fowl (Galgal4) using reference based genome alignment with NGen program of the Lasergene software package. The potential causal single nucleotide polymorphisms (SNPs) showing non-synonymous changes in coding DNA sequence regions were chosen in each line. Bioinformatic analyses to interpret functions of genes retaining SNPs were performed using the ingenuity pathways analysis (IPA). RESULTS: Millions of SNPs were identified and totally 2,884 SNPs (1,307 for HMC and 1,577 for LMC) showing >75% SNP rates could induce non-synonymous mutations in amino acid sequences. Of those, SNPs showing over 10 read depths yielded 15 more reliable SNPs including 1 for HMC and 14 for LMC. The IPA analyses suggested that meat color in chickens appeared to be associated with chromosomal DNA stability, the functions of ubiquitylation (UBC) and quality and quantity of various subtypes of collagens. CONCLUSION: In this study, various potential genetic markers showing amino acid changes were identified in differential meat color lines, that can be used for further animal selection strategy.

[The association between the characteristics of egocentric network and HIV prevalence among men who have sex with men].

Objective: This study aimed to analyze the association between the characteristics of egocentric network and HIV prevalence among men who have sex with men (MSM) through social network analysis. Methods: The study was conducted in Guangzhou city from November 2016 to June 2017 using convenient sampling method. Participants were recruited from 13 voluntary counseling and testing (VCT) locations. Data were collected by using nomination generation and nomination interpretation methods. Questionnaire includes two parts, the first part about the social tie, and the second one about social demography and behavioral characteristics of respondents and their nominees. The multivariate logistic regression was applied to quantify the association. Results: 8.67%(93/1 073) HIV antibody positive MSM had been detected in 1 073 respondents who nominated 4 301 partners in total. Compared to egocentric sexual network with a size of 1-2, the size of sexual network larger than 3 (OR=1.68, 95%CI: 1.07-2.65) were associated with HIV infection. Compared to egocentric risk sexual network with a size of 1-2, the size of risk sexual networks larger than 3 (OR=1.87, 95%CI: 1.06-3.31) were associated with HIV infection. There were no significant association between marital similarity of respondents and their nominees, the type of the relationship of sexual partners and HIV prevalence (P>0.05). Conclusion: The composition of social network in MSM is related to their susceptibility of HIV infection. MSM population with a large sexual network is more susceptible to HIV infection.

Association between polymorphisms of the CRH and POMC genes with economic traits in Korean cattle (Hanwoo).

The corticotrophin-releasing hormone (CRH) and proo-piomelanocortin (POMC) genes are considered to play an important role in the growth and development of mammals. In this study, the bovine CRH and POMC genes were characterized to detect genetic variation at these loci in relation to economic traits in Korean cattle (Hanwoo). Nine single nucleotide polymorphisms (SNPs; C148T, A186G, A234C, G269A, G1030A, G1084A, A1136C, G1179C, and A1439G) were detected in the CRH gene, and six SNPs (C7017T, A7027T, C7050T, G7063T, C7160T, and C7221T) were detected in the POMC gene. Three SNPs in the CRH gene (G1030A, G1084A, and G1179C) were missense mutations, and three SNPs in the POMC gene (C7017T, A7027T, and C7160T) were missense mutations. Statistical analysis indicated that one CRH polymorphism (G1084A) was signifi-cantly (P = 0.05) associated with the longissimus dorsi muscle area (LMA), and a POMC polymorphism (C7221T) significantly influenced LMA and marbling scores. A significant interaction was detected be-tween CRH and POMC in relation to carcass weight and LMA. These results indicate that CRH and POMC may be candidate genes for car-cass traits, and suggest that the interaction between CRH and POMC strongly affects carcass traits in cattle.

Association of vitamin D-binding protein variants with chronic obstructive pulmonary disease: a meta-analysis.

Gene polymorphism of vitamin D-binding protein (VDBP) correlates with chronic obstructive pulmonary disease (COPD), but the results remain inconclusive. We aimed to explore the association between VDBP gene polymorphism and COPD. We searched MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure for publications addressing the association between VDBP gene polymorphism and COPD. After qualitative evaluation, randomized controlled trials were pooled using either a fixed- or a random-effect model depending upon the degree of heterogeneity. Eleven studies with 3144 subjects were included. The genotype group-specific component (GC)*1F-1F was significantly associated with COPD in Asians [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.07-2.81, P = 0.03], but not in Caucasians (OR = 1.44, 95%CI = 0.57-3.66, P = 0.45). A protective effect of GC*1F-1S was observed in Asians (OR = 0.70, 95%CI = 0.55-0.89, P = 0.003) but not in Caucasians (OR = 0.93, 95%CI = 0.69-1.24, P = 0.61). There was no association of GC*1S-1S, GC*2-1S and GC*1F-2 with COPD. As for alleles, GC*1F was a risk factor, whereas GC*1S was protective against COPD in Asians; GC*2 was not protective. The genotype GC*1F-1F or allele GC*1F was associated with increased susceptibility to COPD in Asians. No protective effect of genotype GC*2-2 against COPD was found. The protective effects of GC*1F-1S and GC*1S were observed in Asians but not in Caucasians. The VDBP gene polymorphism could be a potential marker for screening of COPD.

Meta-analytical association between angiotensin-converting enzyme gene polymorphisms and sarcoidosis risk.

Previous reports identified an association between sarcoidosis and an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme. Our meta-analysis of articles published between March 1996 and June 2013 identified studies in the PubMed, EMBASE, and the China National Knowledge Infrastructure databases. We examined whether angiotensin-converting enzyme polymorphisms influence sarcoidosis susceptibility. The strength of the association between I/D polymorphisms and sarcoidosis risk was measured based on the odds ratio and 95% confidence interval. Analysis was based on recessive and dominant models. Ethnic subgroup analysis from 18 articles (1882 cases and 3066 controls) showed that DD homozygote carriers were at a slightly increased risk of sarcoidosis compared with II homozygotes and DI heterozygotes (P = 0.03). Comparison of DD plus DI vs II revealed no significant association with sarcoidosis in group and ethnic subgroup analysis. We found that the I/D polymorphism in the angiotensin-converting enzyme gene was not associated with a major risk of sarcoidosis.

Epsilon-aminocaproic acid improves postrecirculation hemodynamics by reducing intraliver activated protein C consumption in orthotopic liver transplantation.

BACKGROUND: Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT. METHODS: Fifty-nine recipients were randomized to receive either EACA (150 mg kg(-1) given intravenously prior to incision, followed by 15 mg kg(-1) h(-1) infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups. RESULTS: No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05). CONCLUSIONS: EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.

Initial design method based on an iterative calculation of aberration and its application to an objective lens for imaging spectrometer.

An initial optical design method based on an iterative calculation of third-order aberration is presented to overcome the problems of the conventional method. The aberrations of each lens group in the optical system are calculated individually and iteratively under the constraint that aberrations of one group compensate for those of the other groups. The stabilities of initial design results have been confirmed and the iterative design method has been applied for the design of optical system with an external entrance pupil for imaging spectrometer. The designed lens corresponds to an objective lens with the aperture of F/1.5 and the focal length of 30 mm.

Trends in the incidence of and survival rates for oral cavity cancer in the Korean population.

OBJECTIVE: This study assessed trends in the incidence of and survival rates for oral cavity cancer in the Korean population. MATERIALS AND METHODS: Data from the Korea Central Cancer Registry were extracted for 10,282 patients diagnosed with oral cavity cancer (C01-C06) between 1999 and 2010 to evaluate the age-standardised incidence rate, annual percentage change (APC) and 5-year relative survival rate (RSR) according to gender and age. RESULTS: In males, the incidence rate slightly decreased [APC of -0.2% (P = 0.6427)]; in females, the incidence rate increased [APC of 3.1% (P < 0.05)]. In males and females, the incidence of oral tongue cancer (C02) significantly increased [APC of 2.2% and 4.1%, respectively (P < 0.05)]. This increase in oral tongue cancer incidence was most prominent in the younger age group (<40 years, APC = 6.1%, P < 0.05). The incidence of buccal cheek cancer increased only among males [APC of 4.8% (P < 0.05)]. The 5-year RSR improved from 42.7% (1993-1995) to 59.5% (2006-2010), corresponding to an increase of 16.8% from 1993 to 2010 (P < 0.05). CONCLUSION: The incidence of oral cavity cancer in females increased, whereas it stabilised or decreased in males. However, the incidence of oral tongue cancer increased in both males and females, especially in the younger age group.

Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report.

WHAT IS KNOWN AND OBJECTIVE: Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular 'danger' to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung. CASE SUMMARY: A 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5 days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1ß and IL-18 in the serum were declined during the therapy. WHAT IS NEW AND CONCLUSIONS: This is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD.

Characterization of novel microsatellite markers derived from Korean rose bitterling (Rhodeus uyekii) genomic library.

Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni's correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.

Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.