[Renal eosinophilic vacuolated tumor: a clinicopathological analysis of seven cases].

Objective: To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT). Methods: Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls. Results: Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO (P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC (P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions: EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

[Current situation and trend of medical laboratory results homogeneity management].

Medical test results are indispensable and important tools in diagnosis and treatment services. It is necessary to promote the homogenization of test results first, because homogenization is the basis for mutual recognition of test results. Mutual recognition of medical test results can help share resources among medical institutions, provide more reliable test results for early prevention, screening and treatment of diseases, and reduce repeated tests, thus improving people's medical experience. In recent years, with the deepening of medical system reform and the promotion of graded diagnosis and treatment, governments have continuously introduced policies of mutual recognition of test results around country. However, homogenization is a prerequisite for mutual recognition of test results, with the emergence of intelligent medicine in the era of internet big data, opportunities and challenges coexist in the development of homogeneity management. In the future, the homogeneity of medical test results will present a trend of digitalization, automation, informatization and intelligence.

[Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia].

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

[Application of ultra-short echo time-T2* component analysis technology in monitoring morphological and biochemical changes of achilles tendon in amateur marathon athletes].

Objective: To explore the value of ultra-short echo time (UTE)-T2* component analysis techniques in dynamic monitoring the morphological and biochemical changes in amateur marathon athletes' achilles tendon before and after the marathon. Methods: Twenty-nine amateur marathon runners were recruited between October 2020 and March 2021 in Zhuhai City, Guangdong Province, including 25 males and 4 females, aged from 24 to 50 (40±6) years old. All volunteers underwent bilateral achilles tendon MRI examination 1 week before the marathon, 48 hours after the race, and 1 month after the race. The shape and signal of the achilles tendon were evaluated by routine T1-weighted, proton density weighted with fat saturation sequence and different echo time (TE) UTE sequence, and the changes of achilles tendon after running was quantitatively analyzed by UTE-T2* sequence. The values of single-component analysis (T2*M), short T2* components (T2*S), and long T2* components (T2*L) and Fraction values were obtained using UTE-T2* sequence. The value of the whole achilles tendon was measured on the sagittal images of achilles tendon, and the Achilles tendon was equally divided into three subregions [muscle-tendon junction (MTJ), middle (MID), and insertion (INS)]. The region of interest was delineated by two radiologists independently. The intra-group correlation coefficient (ICC) was used to evaluate the consistency of the data measured by two radiologists. Nonparametric Friedman M test was used to compare the differences of T2*M, T2*S, T2*L and Fraction values in different time points and different subregions. Wilcoxon rank-sum test was used to compare the difference between 48 h post-race and pre-race T2*S values (ΔT2*S) of different distance, different running posture, different pace and different amount of training, in which ΔT2*S equals the T2*S value of 48 h post-race minus the T2*S value of pre-race. Results: On the sequence of short TE (TE≤0.6 ms), achilles tendinopathy can manifest as scattered punctate hypointensity in areas of high signal intensity. The two radiologists showed a good consistency in measuring the T2*M, T2*S, T2*L and Fraction values of the achilles tendon, and the ICC values ​​were 0.96, 0.94, 0.83 and 0.94, respectively. The T2*s values was significantly higher in the whole Achilles tendon, MTJ and MID segment at 48 h post-exercise compared to pre-exercise, and decreased after 1 month of exercise, [0.49 (0.45, 0.59) vs 0.54 (0.49, 0.59) vs 0.53 (0.49, 0.57), 0.48 (0.44, 0.54) vs 0.53 (0.47, 0.58) vs 0.50 (0.46, 0.57), 0.48 (0.43, 0.58) vs 0.54 (0.47, 0.59) vs 0.52 (0.46, 0.57); respectively, all P<0.05]. The changes in T2*M, T2*L and Fraction values are not statistically significant (all P>0.05). In different running gestures, the ΔT2*S of achilles tendon who using the postures of front-middle feet is higher than that using the postures of back feet (0.03(-0.05, 0.07) vs -0.03(-0.17, 0.11), P=0.001). Conclusion: The Bi-component analysis of UTE-T2* technology is superior to single component analysis in monitoring the dynamic changes of achilles tendon before and after exercise, and T2*S is a more sensitive sequence to evaluate the subtle changes in the chemical composition of achilles tendon.

LINC00839 Promotes the Progression of Gastric Cancer by Sponging miR-1236-3p.

In this paper, LINC00839 expression in gastric cancer (GC) was confirmed by real-time quantitative PCR. The function of LINC00839 in GC was detected by loss of function assays. Luciferase assays was performed to confirm the interaction between LINC00839 and miR-1236-3p. Then we investigated the regulatory effect of LINC00839 on miR-1236-3p. The results confirmed that the expression level of LINC00839 in GC was significantly up-regulated. LINC00839 could promote GC cell proliferation, mobility, and invasion. The detection of luciferase reporter gene confirmed that LINC000839 could bind to the binding site of miR-1236-3p. Our findings suggest that LINC00839 promotes GC progression through sponging miR-1236-3p.

[Application of immunohistochemical staining of PRAME in differential diagnosis between melanoma and melanocytic nevus].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) in differential diagnosis of benign and malignant cutaneous melanocytic lesions. Methods: Fifty-nine cases of melanoma (50 cases of skin primary melanoma, and 9 cases of metastatic melanoma) and 48 cases of melanocytic nevus (40 cases of common nevus and 8 cases of dysplastic nevus) were subject to PRAME immunohistochemistry staining.The difference of PRAME expression between melanoma and melanocytic nevus was analyzed. Results: Among the 50 patients with primary cutaneous melanoma, there were 23 males and 27 females ranging in age from 33 to 87 years (average age 62.4 years, median age 64.5 years). Among the 9 metastatic melanoma there were 7 males and 2 females ranging in age from 40 to 82 years (average age 64 years, median age 65 years). Twenty-six cases (26/50, 52.0%) of cutaneous primary melanoma and 4 cases (4/9) of metastatic melanoma showed diffuse positive PRAME staining. 40 cases (40/40, 100%) of common nevus and 8 (8/8) cases of dysplastic nevus were PRAME negative. Compared with melanocytic nevus group, the melanoma group included more cases with diffuse positive PRAME staining (P<0.05). The sensitivity and specificity of using PRAME to differentiate primary cutaneous melanoma from melanocytic nevus in the cohort is 52.0% and 100%. Conclusions: There is a significant difference in the expression of PRAME between melanoma and melanocytic nevus.Thus, PRAME can be used as an auxiliary diagnostic tool for differentiating benign from malignant cutaneous lesions.

[Clinicopathological features and diagnosis of pericytic tumors of the kidney].

Objective: To investigate the clinicopathologic features,diagnosis and prognosis of pericytic tumor of the kidney. Methods: Three cases of pericytic tumor of the kidney (two cases were diagnosed as glomangiomyomas and one case as pericytic tumor,unclassified) were collected from the affiliated Hospital of Qingdao University between January 2014 to May 2021; the clinical and morphologic features, immunohistochemical and molecular characteristics were analyzed and the relevant literature was reviewed. Results: The three patients included one male and two females, with ages ranging from 21 to 70 years. In two patients the tumors were detected incidentally at physical examination and one patient presented with low back discomfort. Imaging showed a rounded nodular soft tissue density shadow in renal parenchyma, and enhancement scan showed uneven delayed enhancement. Grossly, two tumors were located in the renal hilum and one in the renal parenchyma; all were nodular. The tumors were measured in size from 1.6 cm to 5.1 cm (mean 4.1 cm) and showed gray or gray-red cut surface. Histologic examination showed the tumor cells were arranged in solid sheets or small nodules, closely related to vascular wall. Tumor cells were mostly epithelial-like with abundant cytoplasm, light eosinophilia, obscure boundary and round nuclei with visible nucleoli. Vague bundles and fascicular arrangements of smooth muscle component were noted in some areas, with transition of both components. There was no necrosis. By immunohistochemistry, the tumor cells strongly and diffusely expressed vimentin, SMA and collagen Ⅳ, two cases expressed CD34, all three cases expressed PDGFRB to varying extent, and the Ki-67 index was 2%-3%. PCR tests showed absent K-RAS, BRAF V600E gene mutation in all three cases. PDGFRB mutations in exons 3 and 18, respectively were found in two of the three cases by high-throughput sequencing, and no NOTCH 1/2/3 gene fusions were found in any of them. Follow-up information (range: 6-92 months) showed no evidence of local recurrence or distant metastasis in all three patients. Conclusions: Pericytic tumor of the kidney is a rare mesenchymal tumor originating in the kidney with differentiation to smooth muscle, most commonly glomus tumor. The mild pleomorphism, close relationship with vascular wall and spindled smooth muscle components suggest the diagnosis of the tumor. Expression of both epithelial and muscle-associated markers aids the diagnosis. PDGFRB gene mutations may have an important role in the development of this tumor. Most patients have a good prognosis, and a few cases have malignant biological behavior.

[Oncocytic papillary renal cell carcinoma: a clinicopathological analysis of nineteen cases].

Objective: To investigate the clinicopathological characteristics, immunophenotype, and molecular signatures of oncocytic papillary renal cell carcinoma (OPRCC), and to compare these findings with those in type 1 papillary renal cell carcinoma (PRCC 1). Methods: The clinicopathologic data of 19 patients with OPRCC from the Affiliated Hospital of Qingdao University (16 patients) and the 971 Hospital of People's Liberation Army Navy (3 patients) from October 2003 to February 2021 were collected. Histologic, immunohistochemical (IHC) and molecular analyses, together with a control group of 15 cases of PRCC I diagnosed in the same period, were assessed. Results: The cohort included 15 males and 4 females, with a median age of 61 years (range, 47-78 years). In 13 patients the tumors were found at physical examination; four presented with painless gross hematuria and two with low back pain. As for the pathologic stage, 14 patients were pT1, one patient was pT2a, three patients were pT3a and one patient was pT4. The tumor size ranged from 1.7-14.0 cm, with clear boundary and soft texture. The cut surface was grayish-yellow and grayish-red. Microscopically, the tumor cells were mainly arranged in papillary (10%-100%) and acinar (tubular) patterns, with strongly eosinophilic cytoplasm, round or irregular nuclei, and prominent nucleoli (WHO/ISUP grade Ⅲ). Two cases showed sarcomatoid differentiation. Stromal foamy macrophages were visible in all cases. IHC staining showed diffuse strong positivity for AMACR in all cases. RCC (18/19), CD10 (17/19), vimentin (16/19) and PAX8 (17/19) were positive in most tumors. CK7 was expressed in about 50% of cases. Fluorescence in situ hybridization identified trisomy 7 in eight patients, trisomy 17 in seven patients, and the two aberrations occurred simultaneously in seven cases. Eight of 13 men had Y chromosome deletion. All patients were followed up for 8-120 months. Three patients died of metastases at 8, 62 and 82 months postoperatively, respectively, and one patient relapsed 36 months after surgery. Compared with PRCC1, OPRCC tended to have higher nuclear grade, and stromal foam cell aggregation was more commonly found (P<0.05). The expression of CD10 and EMA were different (P<0.01). There was no significant difference in the survival rate between the two groups (P=0.239). Conclusions: OPRCC has unique morphologic features, and its immunophenotype overlaps but differs from PRCC1. The molecular results support that it belongs to a morphologic variation of PRCC. This tumor has similar biologic behavior to PRCC1, and has a poor prognosis when sarcomatoid differentiation occurs.

[Whole exome sequencing reveals molecular mechanisms of clear cell renal cell carcinoma with sarcomatoid differentiation].

Objective: To investigate the molecular mechanisms of clear cell renal cell carcinoma (CCRCC) with sarcomatoid differentiation (CCRCCS) and to explore new therapeutic targets for CCRCCS. Methods: Whole exome sequencing was performed on the carcinomatous and sarcomatoid components of five CCRCCS cases collected from January 2017 to October 2018. A highly frequent non-synonymous mutation of cadherin 23 (CDH23) was revealed by whole exome sequencing and further studied in additional samples. The sequencing of CDH23 in 40 specimens with CCRCCS and 50 specimens with CCRCC collected from January 2008 to October 2018 were conducted using Sanger sequencing. Immunohistochemistry was carried out to detect the protein expression of CDH23 in the additional 90 cases. Results: Carcinomatous and sarcomatoid components of CCRCCS shared most of the somatic single-nucleotide variants (SSNVs) as revealed through whole exome sequencing, while the sarcomatoid component had higher overall SSNVs than carcinomatous component. A highly frequent non-synonymous mutation of CDH23 (p.Arg1804Gln) was observed both in carcinomatous and sarcomatoid components of CCRCCS that resulted in the alteration in the highly conserved calcium-binding site mediating the functions of cadherins. In the additional 90 specimens, CDH23 mutation was much frequently detected in CCRCCS than that in CCRCC samples and even the high grade CCRCC. CDH23 protein was not or weakly expressed in most CCRCCS specimens with CDH23 mutation. There was an correlation between CDH23 gene mutation and negative expression of its protein (r=0.598, P<0.01). Conclusions: The present study reveals, for the first time, that the mutation of CDH23 (p.Arg1804Gln) is a genetic risk factor for CCRCCS. It is associated with the decreased expression of CDH23 protein, resulting in the absence of cadherin function of CDH23, indicating that CDH23 mutation may be involved in the sarcomatoid transformation in CCRCCS. Thus, CDH23 might be a potential therapeutic target for CCRCCS.

[Quantitative analysis of non-alcoholic fatty liver disease based on MRI proton density fat fraction in the coastal region of Qingdao].

Objective: To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD). Methods: 178 volunteers from March 2019 to February 2020 were included. PDFF values ​​of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups. Results: 178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value (P > 0.05). PDFF values ​​of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ​​of SVI and SVII liver segments were all higher than the average value (P ​​< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion: Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.

[Clinicopathological features and differential diagnosis of eosionphilic chromophobe renal cell carcinoma].

Objective: To investigate the clinicopathological characteristics of eosionphilic Chromophobe renal cell carcinoma (eChRCC), and differences in morphology, immunophenotype and clinical prognosis betweeneChRCC, renal oncocytoma(RO) and classic Chromophobe renal cell carcinoma (cChRCC). Methods: The clinicopathologic data of 17 patients diagnosed as eChRCC from the Affiliated Hospital of Qingdao University (13 cases) and 971 Hospital of PLA Navy (4 cases) from October 2006 to February 2019 were collected. Immunohistochemical analysis was carried out to compare the immunophenotypes between 17 cases with ChRCC, 27 cases with RO and 30 cases with cChRCC. Resuls: Among the 17 patients, seven were males and ten were females, and the age ranged from 40 to 75 years (median 54 years). Clinically, 15 cases of 17 were found accidentally by physical examination. The tumor size ranged from 1.8 cm to 10.0 cm (average 5.7 cm) and the cut surface of 15 cases were solid, one case was solicl and cystic, and one was cystic. Most showed gray to red, and partially soft, gray to yellow appearances. Microscopically, most tumors presented solid growth pattern with vary number of alveolar structures (12 cases). Some were predominately characterized by cystic structure (3 cases), alveolar structure(1 case) and microcapsule structure (1 case). There were boundaries with varying degrees of clarity between tumor cells in 16 cases. The cytoplasm of tumor cells was eosinophilic and the nuclei were small round or irregular with focal perinuclear haloes in 14 cases. Large polygonal cells with light-stained cytoplasm appeared focally in 9 cases, and edematous areas with scarce tumor cells were found in 4 cases. Among 7 cases, 4 cases focally invaded peripheral renal parenchyma, 2 cases invaded adipose tissues outside the renal capsule, and 1 case presented invasion of renal sinus. Immunohistochemically, all cases were moderate to strong positive for EMA and claudin-7. CK7, CD117 and Ksp-cad were highly expressed with the expression rates of 12/17, 15/17, 14/17, respectively. Cyclin D1, AMACR, CD10, S100A1, and RCC were rarely expressed with the expression rates of 4/17, 3/17, 4/17, 1/17 and 1/17, respectively. On the contrary, all cases were negative for vimentin, CAⅨ, HMB45 and Melan A. The Ki-67 proliferation index of the 17 cases was 1%‒5%. Follow-up data were available for all 17 patients from 7 to 154 months. Among them, 15 patients were alive without tumor recurrence or metastasis, one patient died of pulmonary metastasis after 31 months of surgery and one patient died of hepatic metastasis after 38 months of surgery. Conclusion: eChRCC has overlapping morphology and immunophenotype with RO. eChRCC is characterized by solid nest or alveolar structure, distinct border between tumor cells, perinuclear halos and lacking of interstitial looseness and edema. Scattered large polygonal cells with light-stained cytoplasm in tumor tissue play a significant role in the diagnosis of eChRCC. The positive expression of CK7, CD117, claudin-7 and Ksp-cad, and negative expression of cyclin D1, S100A1 are helpful to the diagnosis and differential diagnosis of eChRCC. The prognosis of eChRCC after complete surgical resection is excellent and few cases may have long-term metastasis. There is no significant difference in prognosis between eChRCC and cChRCC, but eChRCC shows better outcome than RO.

Expression of proteinase-activated receptor-2 and transient receptor potential A1 in vagal afferent nerve of rat after lung schemia-reperfusion injury.

Lung ischemia-reperfusion injury (LIRI) is a common and severe clinical complication. As the injury occurs, the pulmonary afferent nerves play an important role in regulating respiratory functions under pathophysiological conditions. The purpose of this study was to examine expression of proteinaseactivated receptor-2 (PAR2) and transient receptor potential A1 (TRPA1) in pulmonary vagal afferent nerves of LIRI and further to determine molecular mediators linking activation of PAR2 and TRPA1. A rat model of LIRI was used. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were employed to examine pro-inflammatory cytokines (PICs, i.e., IL-1ß, IL-6 and TNF-α), and the protein levels of PIC receptors, PAR2, TRPA1, and intracellular signals. In the results, IL-1ß, IL-6 and TNF-α along with their receptors were amplified in afferent nerves of LIRI rats as compared with control rats. Sensory PAR2 and TRPA1 were also upregulated by LIRI. Blocking PAR2 by infusion of FSLLRY-NH2 attenuated upregulation of TRPA1 via intracellular signals, namely p38-MAPK and JNK. Moreover, blocking individual PIC receptor attenuated PAR2 and TRPA1 in pulmonary vagal afferent nerves. Our data showed specific signaling pathways leading LIRI to activation of PIC signal and activation of PAR2 and TRPA1 in pulmonary vagal afferent nerves via intracellular mediators. Targeting one or more of these signaling molecules may present opportunities to improve the abnormalities in vagal afferent nerve-mediated respiratory functions observed as LIRI occurs.

Genetic association between the NLRP3 gene and acne vulgaris in a Chinese population.

BACKGROUND: Acne vulgaris is a common chronic skin disease. Inflammation is an important pathogenetic mechanism of acne, and NLRP3 polymorphisms have been reported to be involved in the mediation and occurrence of the inflammation. However, only a few studies on NLRP3 and acne have been reported, and the mechanism remains unclear. AIM: To investigate two SNPs in the NLRP3 gene in patients with acne vulgaris (AV) and healthy controls (HCs) in a Chinese population. METHODS: A case-control study was performed with 428 patients with AV and 384 (HCs). The SNPs rs10754558 and rs4612666 of the NLRP3 gene were genotyped using PCR with sequence-specific primers. A dual luciferase reporter assay was performed to determine whether the SNP rs10754558 might be responsible for the altered NLRP3 gene expression in AV by disrupting the interaction between micro-RNA (miR)-4273 and NLRP3 mRNA. Additionally, the mRNA level of NLRP3 was measured by PCR in the two groups. RESULTS: The frequencies of the G allele of rs10754558 were 0.54 in patients and 0.49 in HCs (P < 0.05). No significant difference was observed for SNP rs4612666. Dual luciferase reporter assay revealed that luciferase activity was downregulated by about 40% when the G allele of rs10754558 coexisted with miRNA-4273, indicating that the G allele might interfere with miR-4273 function and alter NLRP3 expression. The level of NLRP3 mRNA in patients with AV was significantly higher than that in HCs. CONCLUSIONS: Our study suggests that the NLRP3 SNP rs10754558 is associated with the incidence of AV. The G allele might be a genetic risk factor for AV in the Chinese population.

Association between frailty and incident risk of disability in community-dwelling elder people: evidence from a meta-analysis.

OBJECTIVE: Frailty is considered to be one of the risk factors of disability. However, the results of original reported studies are not consistent with respect to the frailty and incidence of disability, and previously published meta-analyses have also shown inconsistent results. This meta-analysis was conducted to investigate the relationship between the different stages of frailty and the incidence of disability by examining updated overall trends in community-dwelling elders. STUDY DESIGN: Cohort studies in English or Chinese based on associations between frailty and incident disability risks that were published from 2000 until the current date were researched using PubMed, Embase, Web of Science, and CENTRAL databases. METHODS: The Q test and I2 statistic were used to examine between-study heterogeneity. Random-effect models were adopted to synthesize the results based on the study heterogeneity. Subgroup analyses were also conducted to explore the possible sources of between-study heterogeneity based on the characteristics of participants. RESULTS: Eighteen cohort studies with 88,906 participants were included in our meta-analyses. Compared with the non-frailty category, the combined relative risks (RRs) (95% confidence interval [CI]) of the disability were 1.66 (1.49-1.85) and 2.53 (2.01-3.14) for the category of prefrailty and frailty, respectively. Results suggested that the incident risk of disability at follow-up times <5 (RR = 3.19, 95% CI = 2.25-4.53) was significantly higher than for follow-up times ≥5 in the frailty category (RR = 2.00, 95% CI = 1.55-2.56). The risk in a sample size of ≥1000 (RR = 2.78, 95% CI = 2.04-3.14) was significantly higher than that when the sample size was <1000 (RR = 1.91, 95% CI = 1.53-2.37) in the frailty group. Compared with a value adjusted for comorbidity, the unadjusted comorbidity was significantly higher in the prefrailty category (1.90 vs. 1.52). Compared with a value adjusted for education, the unadjusted education was significantly higher in the prefrailty category (1.81 vs. 1.46). No publication bias was observed. CONCLUSION: The overall meta-analysis confirms that frailty has significantly increased the incident risk of disability. Frail, elderly people are at the highest risk of future disability and may be adequate candidates for taking part in prevention and intervention programs.

[Analysis of adverse events of clinical blood use except for the adverse reactions of blood transfusion].

Objective: To reduce the occurrence of adverse events of clinical blood use by analyzing the clinical adverse events of blood use except for the adverse reactions of blood transfusion. Methods: A retrospective analysis was performed on 294 cases of adverse events of clinical blood use other than adverse blood transfusion reactions in Shijitan hospital from January 2014 to December 2017, and a statistical analysis was made on the types of adverse events of clinical blood use, blood transfusion related departments, and internal and surgical blood use. Results: The incidence of adverse events of clinical blood use was 10.3‰, 9.6‰, 4.2‰ and 4.6‰ in these 4 years respectively, and there were 216 cases (73.5%) of external departments, 49 cases (16.7%) of internal departments, 8 cases (2.7%) of nursing departments, and 21 cases of others(7.1%), which includes 12 cases of errand department, 4 cases of the clinical laboratory and 5 cases of transfusion department. The adverse events of clinical blood use were divided into 4 types: 71 cases (24.1%) of transfusion process problems, 36 cases (12.2%) of clinical communication between departments, 182 cases (61.9%) of clinical unreasonable transfusion and 5 others (1.8%). There were statistically significant differences in the occurrence of adverse events of different types of blood use in external and internal departments based on the property of the department, among which there were significant differences in unreasonable transfusion between them. According to the purpose of blood use, there were statistically significant differences in the occurrence of different types of adverse events between the two departments, and the incidence of different types of external departments were higher than that of internal departments. Conclusions: The incidence of adverse events of blood use in external departments is higher than that in internal departments. Reasonable transfusion should be strengthened to avoid the occurrence of adverse events of clinical blood use, so as to ensure the safety of blood transfusion.

[Renal cell carcinoma in patients with end-stage renal disease: a clinicopathological analysis].

Objective: To investigate the clinicopathological characteristics and prognosis of renal cell carcinoma (RCC) in patients with end-stage renal disease (ESRD). Methods: The clinicopathological data of patients of renal cell carcinoma arising in end-stage renal disease were collected from the Affiliated Hospital of Qingdao University (ten cases) and 971 Hospital of PLA Navy (five cases) from January 2009 to August 2018. Results: Among 15 patients, 14 were male and 1 was female, and the age ranged from 38 to 78 years (mean 51 years, median 49 years). All patients had history of chronic renal failure (7-192 months), including 9 patients treated with hemodialysis for 6 to 132 months. In 12 cases the tumor border was distinct and the tumor size ranged from 1.8 to 11.0 cm. Two cases were multifocal and one case showed extensive renal hemorrhage with an inconspicuous tumor mass. Microscopically, 9 cases were clear cell reanl cell carcinoma including one with sarcomatoid differentiation, 4 were acquired cystic kidney disease-associated(ACKD-RCC) and two were papillary renal cell carcinoma. All patients had a follow-up of 3 to 120 months. Four patients died during a follow-up of 6 to 60 months (mean 30 months) as a result of extensive distant metastases (two cases) and renal failure (two cases), while other eleven patients were alive without tumor recurrence or metastasis (median 40.8 months of follow-up ranging from 3 to 120 months). Conclusions: ESRD-RCC is more often seen in younger male patients. The time intervals from the onset of chronic renal failure to the diagnosis of renal cell carcinoma differ and tumors are frequently incidental findings. The histological types can be sporadic renal cell carcinoma or unique ACKD-RCC. Tumors are often hemorrhagic and necrotic. Routine physical examination and early detection could benefit ESRD-RCC patients. ESRD-RCC may have a favorable prognosis despite of a large tumor size or the presence of sarcomatoid differentiation.

[Clinicopathological characteristics of fumarate hydratase-deficient renal cell carcinoma].

Objective: To investigate the clinicopathologic characteristics, molecular and genetic features, differential diagnoses and prognosis of fumarate hydratase-deficient renal cell carcinoma (FH-RCC). Methods: The immunohistochemical (IHC) expression of FH in 391 renal neoplasms in tissue chips collected from the Affiliated Hospital of Qingdao University and 971 Hospital of PLA Navy from January 2011 to December 2017 was evaluated. The clinicopathologic data of eight FH negative cases were collected.Polymerase chain reaction (PCR) and sequencing were used to detect the changes in FH gene in three cases. Interphase FISH with a dual color and break-apart probe was applied to detect the TFE3 gene alteration in the cases showing TFE3 protein expression. Results: Among the eight patients, seven were male and one was female, and age ranged from 28 to 50 years (mean 39 years). Tumor size ranged from 3.5 cm to 12.0 cm (mean 7.9 cm). Renal pelvis invasion was identified in six cases, and the tumor emboli in renal vein and inferior vena cava were found in four patients. The cut surface of most tumors was solid, colorful, grayish white or yellow with no clear border showing invasive growth pattern. Microscopically, the tumors showed different proportions of papillary, tubular cystic, cribriform and solid structures. The tumor cells were rounded or polygonal with eosinophilic or amphotropic cytoplasm, round or oval nuclei, and focal large and prominent nucleoli (WHO/ISUP grade 3-4). Two cases had sarcomatoid or rhabdoid components. Intravascular tumor emboli were found in five cases. IHC staining showed most tumors expressed PAX8(7/8), CK19(7/8), vimentin (6/8) and P504s(8/8). However, other immunomarkers including CK7, CD10, CD117, RCC, 34ßE12, HMB45 and Melan A were all negative. Sequencing showed all three cases had FH gene mutations in exon 1. FISH revealed no TFE3 gene translocation or amplification in the two cases with TFE3 IHC expression. Follow-up data were available in seven patients with the follow-up period from 11 to 66 months. Among them, five patients died between 11 to 31 months after the surgery because of extensive distant metastases of the tumor to the lung, liver and lymph nodes. The other two patients were alive at the 36th and 66th month after the surgery. Conclusions: Morphologically, FH-RCC overlaps with papillary RCC, collecting duct carcinoma and tubular-cystic RCC, showing a mixture of papillary, tubular cystic, cribriform or tubular papillary structures with at least focal large and prominent nucleoli. The negative expression of FH and the detection of FH gene mutation could facilitate the diagnosis of the tumor. FH-RCC is a high aggressive tumor, prone to metastasize, and is associated with poor prognosis. The timely diagnosis of FH-RCC could benefit the patients and their relatives as well.

Enhanced normal-incidence Goos-Hänchen effects induced by magnetic surface plasmons in magneto-optical metamaterials.

Goos-Hänchen (GH) effects at normal incidence are investigated for metamaterials consisting of an array of ferrite rods. A new effective-medium approach is presented and applied to retrieve the effective parameters of the magneto-optical (MO) metamaterials based on a transformation method. Giant normal-incidence Goos-Hänchen (NIGH) shifts on total reflection and enhanced magnetic switching effects are predicted near magnetic surface plasmon (MSP) resonances for structures with small effective permittivity. Numerical simulations are performed and the results are in good agreement with those from the transformation effective-medium approach.

[Clinicopathological characteristics and prognosis analysis with Paget's disease of the breast].

Objective: The aim of this study was to explore the clinicopathologic characteristics and prognostic factors of Paget's disease. Methods: 137 patients with Paget's disease of the breast who were diagnosed in Cancer Hospital Chinese Academy of Medical Sciences between January 2007 and May 2016 were identified and included in the study, including 134 females and 3 males. Results: The average age at onset of the disease was 51.8 years(range, 27-78 years). Among the 137 patients, 7 cases were Paget's disease without any other underlying malignancy, who were alive during the follow-up period. The other 130 patients were diagnosed with Paget's disease and underlying ductal carcinoma in situ (DCIS) or (and) with an invasive carcinoma. The positive expression rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were 29.2%(40/137), 38.0%(52/137)and 78.1%(107/137), respectively. The two-year and five-year overall survival were 99.0%, 96.0%, and disease-free survival of two-year and five-year were 97.6%, 92.8%, respectively for all 137 patients. On survival analysis, longer course of disease, HER-2 positivity, tumor stage(T1-T4), and axillary lymph node metastasis were significantly associated with overall survival. Conclusions: Paget's disease of the breast is a slowly progressive malignancy with good prognosis. A longer course of disease, HER-2 positivity, tumor stage, axillary lymph node metastasis and distant metastasis were significantly associated with poor prognosis.

[Acquired cystic kidney disease-associated renal cell carcinoma: a clinicopathologic study of three cases].

Objective: To study the clinicopathologic, immunohistochemical (IHC), histogenetic and prognostic features of acquired cystic kidney disease-associated renal cell carcinoma (ACKD-RCC). Methods: Three cases of ACKD-RCC, including two from 401 Hospital of PLA and one from the Affiliated Hospital of Qingdao University were studied by clinical, histological and IHC analysis with review of relevant literature. Results: All the three patients were male, ranging from 46 to 78 years old. All patients had history of chronic renal failure; two patients were treated with hemodialysis for 9 years and 11 years, respectively. In two cases the tumor sizes were 2.5 cm and 3.5 cm, respectively, and the tumor border was distinct. The remaining case showed extensive renal hemorrhage with an inconspicuous mass. Microscopically, the tumor cells were arranged in cribriform, microcystic or acinar structures, with variable papillary structure in one case. Hemorrhage of varying degrees was seen in all three cases, and obvious necrosis was noted in two. The tumor cells had deeply eosinophilic cytoplasm, indistinct cell border, round or oval nuclei, and prominent nucleoli (WHO/ISUP grade 3). Mitoses were rare. Abundant oxalate crystals were seen in two cases. The renal mesenchyme of all three cases were atrophic with variable cystic changes of the renal tubules, the lining cells showed atypical hyperplasia. IHC staining showed all tumors were diffusely positive for vimentin, CD10, RCC, CAM5.2, P504s and mitochondria in the cytoplasm, and were variably positive for EMA (2/3), CK7 (1/3), CA9 (1/3) and PAX8 (3/3). All cases were negative for CD117, HMB45, Melan A and TFE3. After 3-14 months follow-up, one patient died from renal failure six months after surgery. The other two patients were alive without tumor recurrence or metastasis. Conclusions: ACKD-RCC is a very rare renal cell carcinoma. The specific cribriform structure, deeply eosinophilic cytoplasm, prominent nucleoli (WHO/ISUP grade 3), and oxalate crystals deposition, associated with the history of ACKD could aid the diagnosis. ACKD-RCC arises from the proximal renal tubule and its histogenesis might be associated with proliferation and malignant change of the atypical epithelial cells of the cystic renal tubules. ACKD-RCC may have a favorable prognosis except for tumors with sarcomatoid differentiation.