[Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis].

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

[Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review].

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×109/L to 3.3×109/L. Magnetic resonance imaging showed thickened skin of both forearms, while T2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×109/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement (n=19), joint dysfunction (n=11), myalgia/muscle weakness (n=9), and peripheral eosinophilia (n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

[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.

[The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis].

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

[The characteristics and associated factors of functional limitation in patients with rheumatoid arthritis].

Objective: To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA). Methods: Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI. Results: A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age (OR=1.019, 95%CI 1.004-1.035),pain VAS (OR=1.820, 95%CI 1.616-2.050), ESR (OR=1.009, 95%CI 1.001-1.017), CDAI (OR=1.080, 95%CI 1.059-1.102) and modified total Sharp score (OR=1.010, 95%CI 1.004-1.015) were associated factors of functional limitation. Conclusion: The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

[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.

Astragalosides modulates contractile function of toad gastrocnemius muscle.

Huangqi (Radix Astragali) is a well-known traditional Chinese herbal medicine, it is an effective treatment for consumptive disease, such as the common cold, diarrhea, fatigue and cardiac diseases. Astragalosides (AST) is the main component of Huangqi. The purpose of this study is to investigate the modulation effect of AST on the skeletal muscle contractile function. Our results showed that the toad gastrocnemius muscle contractile response was significantly increased after the use of AST (25 mg/L, bath for the isolated muscle), which produced a left-ward shift of the contractile force-stimulation intensity curve. Moreover, AST also prevented the repetitive stimulation-induced decrease in muscle contractile force and recovery amplitude of muscle contraction. These results demonstrate that AST can affect contractile performance of toad gastrocnemius muscle and contribute to skeletal muscle anti-fatigue.

[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.