Time-reversal symmetry-breaking charge order in a kagome superconductor.

The kagome lattice1, which is the most prominent structural motif in quantum physics, benefits from inherent non-trivial geometry so that it can host diverse quantum phases, ranging from spin-liquid phases, to topological matter, to intertwined orders2-8 and, most rarely, to unconventional superconductivity6,9. Recently, charge sensitive probes have indicated that the kagome superconductors AV3Sb5 (A = K, Rb, Cs)9-11 exhibit unconventional chiral charge order12-19, which is analogous to the long-sought-after quantum order in the Haldane model20 or Varma model21. However, direct evidence for the time-reversal symmetry breaking of the charge order remains elusive. Here we use muon spin relaxation to probe the kagome charge order and superconductivity in KV3Sb5. We observe a noticeable enhancement of the internal field width sensed by the muon ensemble, which takes place just below the charge ordering temperature and persists into the superconducting state. Notably, the muon spin relaxation rate below the charge ordering temperature is substantially enhanced by applying an external magnetic field. We further show the multigap nature of superconductivity in KV3Sb5 and that the [Formula: see text] ratio (where Tc is the superconducting transition temperature and λab is the magnetic penetration depth in the kagome plane) is comparable to those of unconventional high-temperature superconductors. Our results point to time-reversal symmetry-breaking charge order intertwining with unconventional superconductivity in the correlated kagome lattice.

Effects of Bulleyaconitine A on Extracellular Matrix Secretion and Expression of Related Proteins in Acetaldehyde-Activated Hepatic Stellate Cells.

Activated hepatic stellate cells differentiate into myofibroblasts, which synthesize and secrete extracellular matrix (ECM) leading to liver fibrosis. It was previously demonstrated that bulleyaconitine A (BLA), an alkaloid from Aconitum bulleyanum, inhibits proliferation and promotes apoptosis of human hepatic Lieming Xu-2 (LX-2) cells. In this study, we analyzed the effect of BLA on the production of ECM and related proteins by LX-2 cells activated with acetaldehyde (AA). The cells were randomized into the control group, AA group (cells activated with 400 µM AA), and BLA+AA group (cells cultured in the presence of 400 µM AA and 18.75 µg/ml BLA). In the BLA+AA group, the contents of collagens I and III and the expression of α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1) were statistically significantly higher than in the control, but lower than in the AA group. Expression of MMP-1 in the BLA+AA group was also significantly higher than in the AA group, but lower than in the control. Expression of TIMP-1 in the BLA+AA group was significantly higher than in the control, but lower than in the AA group. Thus, BLA suppressed activation and proliferation of LX-2 cells by inhibiting TGF-ß1 signaling pathway and decreasing the content of collagens I and III by reducing the MMP-1/TIMP-1 ratio.

[Correlation of posterior segment lesions with anterior segment biometric parameters and FBN1 genotype in patients with Marfan syndrome].

Objective: To investigate the characteristics of posterior segment lesions in Marfan syndrome (MFS) patients and their relationship with anterior segment biometric parameters and FBN1 genotype. Methods: A cross-sectional study was conducted. A total of 121 MFS patients, 76 males and 45 females, with an average age of (11.72±11.66) years, who visited the Department of Ophthalmology, Eye & ENT Hospital of Fudan University from January 2013 to March 2023 were included. The presence of posterior scleral staphyloma was observed using B-mode ultrasound, and macular lesions were identified and classified using the atrophy-traction-neovascularization system based on ultra-widefield fundus images, color fundus images, and optical coherence tomography scans. Anterior segment biometric parameters, including axial length of the eye, average corneal curvature, corneal astigmatism, horizontal corneal diameter, anterior chamber depth, and lens thickness, were collected, and the direction and extent of lens dislocation were observed. Molecular genetic analysis of FBN1 gene mutations in patients was performed using next-generation sequencing based on a panel of ocular genetic diseases, and the impact of the genotype and anterior segment biometric parameters on the posterior segment manifestations was analyzed. Results: Sixty patients exhibited posterior segment lesions, including retinal detachment (4 cases, 3.31%), macular lesions (47 cases, 38.84%), and posterior scleral staphyloma (54 cases, 44.63%). There was statistically significant difference in axial length of the eye between patients with and without posterior scleral staphyloma [23.09 (22.24, 24.43) and 27.04 (25.44, 28.88) mm], between patients with and without macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.78) mm], and between patients with and without atrophic macular lesions [23.16 (22.24, 24.61) and 27.04 (25.74, 28.79) mm] (all P<0.001). There was statistically significant difference in anterior chamber depth between patients with and without macular lesions [3.11 (2.75, 3.30) and 3.34 (3.09, 3.60) mm] (P<0.05). There was also statistically significant difference in corneal astigmatism between patients with and without posterior scleral staphyloma [2.15 (1.20, 2.93) and 1.40 (1.00, 2.20) diopters] (P<0.05). The location and region of the FBN1 gene mutation not only showed statistically significant difference from the positive rates of posterior scleral staphyloma and macular lesions (all P<0.05), but also influenced the occurrence of atrophic macular lesions (both P<0.05). Patients with FBN1 mutations located in the transforming growth factor ß regulatory sequence had the highest proportion of posterior scleral staphyloma and macular lesions (both 10/11). Conclusions: Posterior scleral staphyloma and macular lesions have a relatively high incidence in MFS patients and tend to progress to more severe grades. The age, axial length of the eye, anterior chamber depth, corneal astigmatism, and location and region of the FBN1 gene mutation are factors affecting the posterior segment lesions in MFS patients.

[Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021].

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

[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.

[Clinicopathological features of hybrid oncocytic/chromophobe renal cell tumor].

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor (HOCT) of the kidney and its associations with renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (eChRCC). Methods: A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of PLA Navy (3 cases), Qingdao, China for morphological studies, immunohistochemical staining and follow-up. The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC. Results: Among the 8 patients, 3 were male and 5 were female. Their ages ranged from 39 to 75 years (median: 56 years). All cases were sporadic. Seven patients were asymptomatic and one suffered from lumbago. During a mean follow-up of 37 months in 7 patients, none of them developed tumor recurrence or metastasis. Seven cases were solitary and one was multiple. The tumor size ranged from 1.4 to 5.7 cm (mean, 3.6 cm). The cut surface of the tumors was dark red or yellowish. Histologically, the tumors were well-defined. Six cases were directly adjacent to the surrounding renal tissue, 2 cases had pseudocapsule, 3 cases showed entrapped renal tubules at the edge of tumor tissue, and one circumscribed with focal infiltrating borders. There were two types of histological morphology: one type (4 cases) was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma; another type (4 cases) showed the morphological characteristics of both RO and eChRCC. Three second-type tumors showed nest-like, trabecular, and solid growth patterns with conspicuous edematous stroma. The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance. The nuclei were small and round with clear perinuclear halo. One tumor showed a multi-nodular and solid growth pattern, and the cytoplasm was eosinophilic, hypochromatic or transparent. The nuclei were small and round, and some of them had obvious perinuclear halo. Immunohistochemically, the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin. CD117 was diffusely positive in 6/8 cases. CK7 staining showed patchy positivity in 6/8 cases. S-100A1, cyclin D1 and claudin7 showed variable positivity in 4/8, 6/8 and 5/8 cases, respectively, but the range and intensity were narrower and weaker than those in RO and eChRCC. Conclusions: HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC. The combined application of immunohistochemical stains of CK7, CD117, Ksp-cad, cyclin D1, claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors. HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.

[The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020)].

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Group of Pancreatic Surgery, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

[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.

[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.

[Medical staff's exposure to solid particles and health impact survey].

Objective: To investigate the current situation of exposure of solid particles in medical staff and the occurrence of related diseases, and to understand the distribution characteristics of occupational exposure and the influencing factors. Methods: In August 2016, the stratified cluster sampling method was adopted to select three tertiary general hospitals with different regions, different administrative levels and departments in Shandong Province. A face-to-face questionnaire survey was conducted on the basic situation of the staff of the hospital, the status of exposure to occupational hazards and the health effects. Two-class logistic regression analysis was used to analyze the relationship between medical staff's solid particle contact and occupational health effects. In August 2016, the stratified cluster sampling method was adopted to select three tertiary general hospitals with different regions, different administrative levels and departments in Shandong Province, which were in contact with the basic conditions and occupational hazards of the staff of the hospital. Current situation and health impacts were conducted face-to-face questionnaires. Two-class logistic regression analysis was used to analyze the relationship between medical staff's solid particle contact and occupational health effects. Results: The overall contact rate of solid particles of medical staff was 41.5% (1843/4 446) , and the solid particles with the highest contact rate were 28.2% (1254/4 446) of talc dust. There was a statistically significant difference in the contact rate of solid particles between medical staff of different occupations, current working age, education and hospital type (χ(2)=76.30, 41.26, 26.16, 188.97, P<0.05) . There were significant differences in the conditions and types of solid particles in different departments (χ(2)=740.23, P<0.05) . Compared with the control group, the incidence of allergic asthma, chronic tracheobronchitis and dermatitis was higher in the contact group medical staff (P<0.05) . Contact with zirconia dust, talc dust, cotton dust is a risk factor for dermatitis in medical staff (OR=2.09, 1.45, 1.34) ; exposure to zirconia dust and cotton dust is a risk factor for chronic tracheobronchitis in medical staff (OR=2.38, 1.66) ; exposure to zirconia dust, gypsum dust is a risk factor for allergic asthma in medical staff (OR=3.90, 1.52) . Conclusion: The contact rate of solid particles in medical staff is high, and there are many types of contact. Frequent contacted with solid particles is a dangerous cause of related diseases. The working environment of medical staff should be further monitored and be strengthen the targeted protective measures and regulatory systems for the exposure of medical personnel to solid particles.

[Clinicopathologic features of primary renal neuroendocrine carcinoma].

Objective: To investigate the clinicopathologic characteristics, diagnostic features and prognosis of primary renal neuroendocrine carcinoma (NEC). Methods: The clinicopathologic data of eight cases of renal NEC was collected from January 2008 to December 2017 from Affiliated Hospital of Qingdao University. Immunohistochemical staining was performed, and follow-up information was analyzed, and the relevant literature reviewed. Results: The patients' mean age at diagnosis was 45 years (range, 27-66 years); five were women, and three were men. The tumors located on the left side in five patients, and on the right side in three. Five cases were detected incidentally, and three patients presented with loin pain. Microscopically, these cases included five well-differentiated NECs (three carcinoids, two atypical carcinoids), two small cell NECs, and one large cell NEC according to the World Health Organization classification of 2016. The tumors infiltrated the renal capsule in six cases. Necrosis was found in five cases. Vascular invasion with tumor emboli was seen in three cases. Lymph node metastasis was identified in one case. Immunohistochemically, the expression rates of neuroendocrine markers CD56, chromogranin A (CgA) and synaptophysin (Syn) were 6/8, 4/8, and 8/8 respectively. Some of the NECs were positive for epithelial markers CKpan (6/8, with three cases showing focal positivity) and CAM5.2 (4/8) of variable degrees. The Ki-67 proliferation index was≤3% in the carcinoids; ≥50% in the small cell carcinoma and large cell carcinoma; and 5% and 8% for the two cases of atypical carcinoid, respectively. All cases were negative for EMA, CK7, CA9, CD10, CD117, PAX2, PAX8, WT1, p63, S-100 and TTF1. Three patients (two with small cell carcinoma and one with large cell carcinoma) died of extensive metastases at 3 months, 4 months and 9 months after operation, while five patients were well, without recurrence or distant metastasis for follow-up period of one to nine years. Conclusions: Primary renal NEC is rare. Carcinoid is the most common histological type. The pathomorphological features and neuroendocrine markers (CD56, CgA, Syn), epithelial markers (CKpan, CAM5.2) and nephrogenic markers (PAX2, PAX8) are important for the diagnosis. Renal carcinoid tumors are indolent and prone to early metastasis, but are associated with prolonged survival. The small cell renal cell carcinoma and large cell carcinoma are highly malignant renal tumors with poor prognosis and short survival.

[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.

[Diagnostic utility of immunohistochemistry in differential diagnosis of renal tumors with oncocytic features].

Objective: To investigate the morphological features and immunophenotypes of eosinophilic renal tumors in order to provide references for the differential diagnosis of this tumor. Methods: A cohort of 75 cases of eosinophilic renal tumors were collected. The morphological features of the tumors were observed under microscope, and the immunophenotypes of the tumors were detected using tissue microarray and immunoshistochemistry. Results: There were some overlaps between the different types of eosinophilic renal tumors in morphology, but each had its distinct characteristics. Immunohistochemically, renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (ChRCC) shared some common immumophenotypes, except for the expression of CK7, with the expression rates of 2/19 in RO and 17/20 in eosinophilic ChRCC, respectively. Eosinophilic clear cell renal cell carcinoma mainly showed positive immunostaining for Vimentin and CAⅨ, whereas negative for CK7 and CD117 in most cases (10/15). AMACR was diffusely expressed in the majority of eosinophilic papillary renal cell carcinoma (PRCC, 10/13). Furthermore, vimentin, CK7 and CD10 were positively expressed in eosinophilic PRCC with the expression rates of 8/13, 9/13 and 6/13, respectively; while CAⅨ, CD117 and TFE3 were all negatively expressed in eosinophilic PRCC.Epithelioid angiomyolipoma generally showed positive expression of vimentin, SMA and HMB45, but negative expression of CAⅨ and CK7. Vimentin, CD10, AMACR and TFE3 were strongly expressed in XP11.2 translocation renal cell carcinoma; on the contrary, CK7, CD117 and HMB45 were not expressed in the majority of the tumor. Conclusion: With full understanding of the morphology of different types of eosinophilic renal tumors, the immunostaining of vimentin, CAⅨ, CK7, CD10, AMACR, CD117, TFE3 and HMB45 could play a crucial role in the differential diagnosis of these tumors.