Assessing the causal role of immune traits in rheumatoid arthritis by bidirectional Mendelian randomization analysis.

Rheumatoid arthritis (RA) is one of the most common autoimmune joint disorders that leads to cartilage degradation. However, its specific correlation with immune cells has not been thoroughly clarified. Based on the two-sample Mendelian randomization (MR) analysis, the association between RA and 731 immune phenotypes which include morphological parameters (MP), relative cell (RC), median fluorescence intensities (MFI), and absolute cells (AC) was comprehensively determined. After false discovery rate correction, RA and immunophenotypes were statistically associated with each other. It was observed that four immune phenotypes, including 1 MPs, 8 RCs, 15 MFIs, and 10 ACs were causally associated with the risk of RA. Meanwhile, several identified immune traits could serve as independent factors for RA and be robust against pleiotropy. While considering the role of RA in immune traits, the involvement of RA in multiple immunophenotypes including CD62L- myeloid DC AC, CD3 on secreting Treg, CD3 on activated and secreting Treg, and CD3 on CD4 Treg was revealed. This study is the first comprehensive evaluation of the interaction between immune response and RA risk, thus providing therapeutic strategies for RA from an immunological perspective.

Soil microbial subcommunity assembly mechanisms are highly variable and intimately linked to their ecological and functional traits.

Revealing the mechanisms underlying soil microbial community assembly is a fundamental objective in molecular ecology. However, despite increasing body of research on overall microbial community assembly mechanisms, our understanding of subcommunity assembly mechanisms for different prokaryotic and fungal taxa remains limited. Here, soils were collected from more than 100 sites across southwestern China. Based on amplicon high-throughput sequencing and iCAMP analysis, we determined the subcommunity assembly mechanisms for various microbial taxa. The results showed that dispersal limitation and homogenous selection were the primary drivers of soil microbial community assembly in this region. However, the subcommunity assembly mechanisms of different soil microbial taxa were highly variable. For instance, the contribution of homogenous selection to Crenarchaeota subcommunity assembly was 70%, but it was only around 10% for the subcommunity assembly of Actinomycetes, Gemmatimonadetes and Planctomycetes. The assembly of subcommunities including microbial taxa with higher occurrence frequencies, average relative abundance and network degrees, as well as wider niches tended to be more influenced by homogenizing dispersal and drift, but less affected by heterogeneous selection and dispersal limitation. The subcommunity assembly mechanisms also varied substantially among different functional guilds. Notably, the subcommunity assembly of diazotrophs, nitrifiers, saprotrophs and some pathogens were predominantly controlled by homogenous selection, while that of denitrifiers and fungal pathogens were mainly affected by stochastic processes such as drift. These findings provide novel insights into understanding soil microbial diversity maintenance mechanisms, and the analysis pipeline holds significant value for future research.

Appropriate timing to perform an interim 18F-FDG PET/CT in patients with nasal-type extranodal natural killer/T cell lymphoma.

Interim 18F-FDG PET/CT (I-PET) has a role in response evaluation and treatment guidance in patients with nasal-type extranodal natural killer/T cell lymphoma (ENKTL). However, there was no agreement on the timing of I-PET performed, after chemotherapy or after chemoradiotherapy. We aimed to find the appropriate timing for I-PET by assessing the prognostic value of I-PET in response evaluation in ENKTL patients. Two hundred and twenty-seven ENKTL patients who had undergone I-PET were retrospectively included. All patients were grouped based on their therapeutic strategy received, chemotherapy or chemoradiotherapy. The Deauville 5-point score (DS) was used to interpret the I-PET images. The hazard ratio (HR) and C-index were used to measure the discriminatory and prognostic capacities of I-PET performed at different times. One hundred and six patients underwent the I-PET after chemotherapy (chemotherapy group), while I-PET was performed after chemoradiotherapy in 121 patients (chemoradiotherapy group). Eighty-seven patients were classified as metabolic remission (DS score of 1-3), while the other 140 were classified as non-metabolic remission (DS score of 4-5) according to the Deauville criteria. There were no significant survival differences between patients in metabolic remission and in non-metabolic remission in either progression-free survival (PFS, p = 0.406) or overall survival (OS, p = 0.350). In the chemotherapy group, patients in metabolic remission had significantly superior PFS than patients in non-metabolic remission (p = 0.012). For OS, a discriminative trend was also found on the survival curve between patients in metabolic remission and in non-metabolic remission (p = 0.082). In the chemoradiotherapy group, there was no significant difference in PFS (P = 0.185) or OS (P = 0.627) between patients in metabolic remission and in non-metabolic remission. I-PET after chemotherapy yields higher discriminative power and has the ability for prognostic prediction in nasal-type ENKTL patients. I-PET after radiochemotherapy has no prognostic value. Thus, the appropriate timing for I-PET is after chemotherapy but before radiotherapy for response evaluation in nasal-type ENKTL patients.

Reforestation substantially changed the soil antibiotic resistome and its relationships with metal resistance genes, mobile genetic elements, and pathogens.

Revealing the effects of reforestation on soil antibiotic resistome is essential for assessing ecosystem health, yet related studies remain scarce. Here, to determine the responses of the soil antibiotic resistome to reforestation, 30 pairs of cropland and forest soil samples were collected from southwestern China, a region with high environmental heterogeneity. All the forests had been derived from croplands more than one decade ago. The diversity and abundance of soil antibiotic resistance genes (ARGs), metal resistance genes (MRGs), mobile genetic elements (MGEs), and pathogens were determined by metagenomic sequencing and real-time PCR. The results showed that reforestation significantly increased soil microbial abundance and the contents of Cu, total carbon, total nitrogen, total organic carbon, and ammonium nitrogen. Nevertheless, it decreased the contents of soil Zn, Ba, nitrate nitrogen, and available phosphorus. The main soil ARGs identified in this region were vancomycin, multidrug, and bacitracin resistance genes. Reforestation significantly increased the soil ARG abundance by 62.58%, while it decreased the ARG richness by 16.50%. Reforestation exerted no significant effects on the abundance of heavy metal resistance genes and pathogens, but it doubled the abundance of MGEs. Additionally, reforestation substantially decreased the co-occurrence frequencies of ARGs with MRGs and pathogens. In contrast, the correlation between ARGs and MGEs was greatly enhanced by reforestation. Similarly, the correlations between soil ARG abundance and environmental factors were also strengthened by reforestation. These findings suggest that reforestation can substantially affect the soil antibiotic resistome and exerts overall positive effects on soil health by decreasing ARG richness, providing critical information for assessing the effects of "grain for green" project on soil health.

Primary Intraosseous Squamous Cell Carcinoma of the Mandible Mimicking Inflammation on FDG PET/CT.

ABSTRACT: Primary intraosseous squamous cell carcinoma (SCC) is an uncommon malignant cancer involving the jaw bones. We herein reported the imaging findings of a primary intraosseous SCC of the mandible in a 47-year-old man. He was diagnosed as cancer of unknown primary in the cervical node. FDG PET/CT revealed a focal hypermetabolic lesion around the tooth root of the right lower molar. MRI showed the lesion had hyperintensity on T2-weighted imaging and significant enhancement on T1-weighted imaging fat saturate images. The final diagnosis of primary intraosseous SCC of mandible was confirmed pathologically.

Intrapatient repeatability of background 18F-FDG uptake on PET/CT.

BACKGROUND: Background activity is often used as a reference to assess tumor treatment response on positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT). Our objective was to find the preferred background by assessing the repeatability of its activity. The activity was expressed by a standardized uptake value normalized to lean body mass (SUL). METHODS: Patients who received repeat 18F-FDG PET/CT scans within 1 to 4 days were selected. The indications included cancer screening, tumor staging, or treatment response evaluation. Background SULs from the aortic blood pool (ABP), liver, and muscle were recorded. Intraclass correlation coefficients (ICCs), the coefficient of variation (CV), and Bland-Altman plots for repeated measures were used to evaluate the degree of repeatability between the two scans. Intrapatient variation in SULs and factors, including the blood glucose level (BGL), tracer uptake period, and dose, were calculated as relative changes between the two scans. A linear regression model was used to analyze all relative changes to identify the correlation between factors and SULs. RESULTS: Thirty patients were included. The SUL ICCs for the ABP, liver, and muscle were 0.65 (95% CI, 0.38-0.81), 0.47 (95% CI, 0.15-0.70), and 0.82 (95% CI, 0.65-0.91), respectively. The SUL coefficients of variation (CVs) were 9% for the ABP, 12% for the liver, and 10% for muscle. Similar results were obtained from the Bland-Altman plots. There was a positive correlation between the variations in the liver SUL and the BGL (b=0.60, P<0.01). A similar result was found between the variations in muscle SUL and the BGL (b=0.45, P<0.01). The variation in muscle SUL showed a positive correlation with the variation in the tracer uptake period (b=0.58, P<0.01). CONCLUSIONS: The SUL of the liver is more sensitive to BGLs and, therefore, may not be suitable as a referential background. Activities within the ABP and muscle are more stable than those of the liver and should be used as the preferred background for sequential patient evaluation.

The effect of hypothyroidism on referential background metabolic activity on 18F-FDG PET/CT.

BACKGROUND: Background uptake activity is used as a reference to assess treatment response by positron emission tomography-computed tomography (PET/CT) with 2-deoxy-2-[F-18]fluoro- D-glucose (18F-FDG). Prior studies have reported decreased liver and increased muscle 18F-FDG uptake in patients with hyperthyroidism. We hypothesized that hyperthyroidism and hypothyroidism might have inverse effects on 18F-FDG uptake on PET/CT. METHODS: We recruited 36 patients with hypothyroidism and 36 age and gender-matched euthyroid participants. We recorded patient factors and background mean standardized uptake values normalized by lean body mass from the aortic blood pool, liver, and muscle. We compared the patient factors and background standardized uptake values normalized by lean body mass between hypothyroidism patients and the controls. We performed a multivariate analysis to determine the best predictors of the 3 different background standardized uptake values normalized by lean body mass. RESULTS: Patients with hypothyroidism had higher liver standardized uptake values normalized by lean body mass (1.77±0.33 vs. 1.58±0.26, P=0.009) and aortic blood-pool standardized uptake values normalized by lean body mass (1.21±0.22 vs. 1.11±0.20, P=0.040) than the controls. In contrast, the muscle standardized uptake value normalized by lean body mass (0.50±0.09 vs. 0.54±0.09, P=0.044) of the patients with hypothyroidism was lower than that of the controls. The serum level of thyroid-stimulating hormone was an independent predictor of liver standardized uptake values normalized by lean body mass (ß=0.356, P<0.001) and blood-pool standardized uptake values normalized by lean body mass (ß=0.288, P=0.001). The serum level of free triiodothyronine was an independent predictor of muscle standardized uptake values normalized by lean body mass (ß=0.310, P=0.002). CONCLUSIONS: PET/CT scans showed that hypothyroidism patients had increased liver and blood-pool 18F-FDG uptake and decreased skeletal muscle 18F-FDG uptake compared with euthyroid individuals. These alterations should be noted when a metabolic response to cancer treatment on PET/CT is determined.

Multiple Myeloma Presenting as Disseminated Osteoblastic Lesions With Intense 18F-FDG Uptake on PET/CT.

ABSTRACT: A 42-year-old woman presented with numbness and weakness in the lower limbs. The radiograph, MRI, and 99mTc-MDP bone scintigraphy revealed multiple bone lesions. The lesions were sclerotic on radiograph. Subsequent 18F-FDG PET/CT showed the lesions were disseminated and had intense 18F-FDG uptake. Monoclonal lambda plasmacytoma was confirmed after CT-guided biopsy of the third lumbar vertebral lesion. The laboratory data also showed a monoclonal immunoglobulin G lambda protein in serum and urine immunofixation. The patient was diagnosed as multiple myeloma finally. Multiple myeloma should be in the differential diagnosis scope of multiple osteoblastic lesions with intense 18F-FDG uptake on PET/CT.

Solitary Hard Palate Langerhans Cell Histiocytosis Demonstrated on PET/CT Scan in an Adult.

Langerhans cell histiocytosis (LCH) is rare in adults. Oral and maxillofacial LCH commonly affects the bones of the skull and jaws. Here we report a case of a 57-year-old man with a painless oral mass evaluated by F-FDG PET/CT. PET/CT showed a solitary F-FDG-avid tumor in his left hard palate. LCH was confirmed after surgery. This case reminds us that LCH should be considered in an adult with hypermetabolic hard palate lesion on F-FDG PET/CT.

Adrenal and Bone Metastases as the Initial Presentation of Endometrial Carcinoma Diagnosed by 18F-FDG PET/CT.

Adrenal and bone metastases as the initial presentation of endometrial carcinoma are rare. We report a case of endometrial carcinoma in a 47-year-old woman with initial manifestation as right chest wall pain, which was suspected as adrenal cortical carcinoma with rib metastasis after diagnostic CT scan. However, uterine and pelvic bone lesions were revealed by staging FDG PET/CT. Eventually, endometrial carcinoma with adrenal and bone metastases was confirmed pathologically.

Mediastinal 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Mediastinal Soft Tissue Giant Cell Tumor.

Soft tissue giant cell tumor (GCT) is rare. It usually involves the extremities. We report the case of a 37-year-old woman who was suspected of having mediastinal tumor on radiograph. Thoracic CT revealed the tumor had extensive calcification and invaded the adjacent vertebrae and spinal canal. It intensively accumulated Tc-methylene diphosphonate on bone scan. The tumor showed hypointensity on T1-weighted and mixed intensity on T2-weighted fat-saturated sagittal images. Finally, a soft tissue GCT was confirmed by pathology. The case cautions us soft tissue GCT should be in the differential diagnosis spectrum in a calcified posterior mediastinal mass with Tc-methylene diphosphonate accumulation.

18F-FDG PET/CT Imaging of Adrenal Liposarcoma.

Liposarcoma is a common soft tissue sarcoma in retroperitoneum, but adrenal liposarcoma is rare. We here described a 61-year-old man with left-upper-quadrant pain, hypertension, and weight loss. Abdominal CT showed a large, heterogeneously enhanced mass on the left adrenal area, which compressed the surrounding pancreas, spleen, and left kidney. Subsequent FDG PET/CT demonstrated heterogeneous uptake by the lesion. Postoperative pathological findings confirmed the diagnosis of adrenal liposarcoma.

Gastric 99mTc-Methylene Diphosphonate Accumulation in a Patient With Primary Upper Gastrointestinal Tract Melanoma.

Unexpected extraosseous uptake is common on Tc-methylene diphosphonate bone scintigraphy, but accumulation by primary upper gastrointestinal tract malignant melanoma is rarely reported. The present case is a 58-year-old woman with a 10-day history of diffuse bone pain and weakness. Her bone scintigraphy showed unexpected diffuse gastric tracer uptake. Subsequent gastroscopy revealed a number of hyperpigmented lesions in the stomach and duodenal bulb. Malignant melanoma was confirmed by histopathology and immunohistochemistry. Because extensive physical examination failed to identify any other site of ocular and cutaneous melanoma, a diagnosis of primary upper gastrointestinal tract malignant melanoma was established.

Isolation, Optimization of Fermentation Conditions, and Characterization of an Exopolysaccharide from Pseudoalteromonas agarivorans Hao 2018.

In recent years, the wide application of exopolysaccharides (EPSs) in food, cosmetics, medicine, and other fields has drawn tremendous attention. In this study, an EPS produced by Pseudoalteromonas agarivorans Hao 2018 was isolated and purified, and its fermentation conditions were optimized. Its structure and biological functions were also studied. The purity and molecular weight of EPS were determined by high performance liquid chromatography (HPLC), and the EPS exhibited a number average of 2.26 × 105 and a weight average of 2.84 × 105. EPS has good adsorption for Cu2+ and Pb2+. The adsorption rates can reach up to 69.79% and 82.46%, respectively. The hygroscopic property of EPS was higher than that of chitosan, but slightly lower than that of sodium hyaluronate. However, the water-retaining activity of EPS was similar to that of chitosan and sodium hyaluronate. EPS has strong ability to scavenge free radicals, including OH radical and O2- radical. Further, its activity on O2- radicals has similarities with that of vitamin C. EPS has broad application prospects in many fields, such as cosmetics, environmental protection.

Isolated Small Bowel Metastasis From Gastric Cancer Detected by 18F-FDG PET/CT.

Small bowel metastasis is rare. Most patients are diagnosed after presenting serious complications. The primary tumors generally arise from breast, lung, and melanoma, but rarely from the stomach. Here we present a case of a gastric cancer patient with asymptomatic small bowel metastasis diagnosed at staging using F-FDG PET/CT. The bowel lesion could not be found on the full-dose CT component of PET/CT. Previous staging contrast CT also made a missed diagnosis. This case reminds us that PET/CT can be used to detect unsuspected metastasis. It may be suitable for routine initial staging, especially on a patient with poor prognosis.

Isolated Vaginal Recurrence of Early-Stage Rectal Cancer Detected by 18F-FDG PET/CT.

The relapses of rectal cancer are most frequently localized in the pelvis, liver, and pelvic and para-aortic lymph nodes and lungs, whereas the vagina is an unusual site. We present here a 60-year-old woman presenting with lower abdominal discomfort 23 months after radical resection of rectal adenocarcinoma. An isolated, solitary, hypermetabolic mass in the right part of the vagina was detected by F-FDG PET/CT. Ultimately, the vaginal neoplasm was proved to be adenocarcinoma of rectal origin based on its shared histologic features and compatible immunostaining profile.

Isolation, Characterization, and Pharmaceutical Applications of an Exopolysaccharide from Aerococcus Uriaeequi.

Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a substantial component of the macro-molecules surrounding cells. Recently, the wide demand for EPSs for food, cosmetics, pharmaceutical and other applications has led to great interest in them. In this study, an EPS produced by marine bacteria Aerococcus uriaeequi HZ strains (EPS-A) was isolated and purified to examine its structure and biological function. The molecular weight of EPS-A analyzed by high-performance liquid gel filtration chromatography (HPGFC) is found to have a number average of 2.22 × 105 and weight average of 2.84 × 105, respectively. High-performance liquid chromatography (HPLC) and Fourier-transform⁻infrared (FT⁻IR) analysis indicate that EPS-A was a polysaccharide composed of glucose and a little mannose. In addition, the flocculating rate of sewage of EPS-A was 79.90%. The hygroscopicity studies showed that hygroscopicity of EPS-A was higher than chitosan but lower than that of sodium hyaluronate. The moisture retention of EPS-A showed similar retention activity to both chitosan and sodium hyaluronate. EPS-A also can scavenge free radicals including both OH• free radical and O2•- free radical and the activity to O2•- free radical is similar to vitamin C. Safety assessment on mice indicated that the EPS-A is safe for external use and oral administration. EPS-A has great potential for applications in medicine due to its characteristics mentioned above.

A false-positive I-131 finding of duodenum diverticulum in thyroid cancer evaluation by SPECT/CT: A case report.

RATIONALE: Iodine-131 (I-131) is a sensitive marker for the detection of differentiated thyroid cancer (DTC). I-131 whole-body scintigraphy (WBS) has been used widely in evaluation of DTC patient. However, I-131 WBS exists many false-positive uptake of I-131 because radioiodine uptake can also be seen in healthy tissue or in a variety of benign and malignant non-thyroidal tumors. PATIENT CONCERNS: A 44-year-old woman with a papillary thyroid carcinoma for the purpose of ablation therapy after a total thyroidectomy. I-131 WBS showed intensive uptake by thyroid remnant. Meanwhile, a focus of increased activity was seen in right upper abdomen. DISGNOSES, INTERVENTIONS AND OUTCOMES: Based on an I-131 single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging combining a Tc-99m pertechnetate dynamic SPECT scan and SPECT/CT fusion imaging with oral administration of iodine contrast agent, a descending duodenum diverticulum was diagnosed. This patient was then treated with conservative treatment, such as diet regulation, rest, appropriate use of antacids and antispasmodic agents, etc. So far, she recovered uneventfully with no any complications. LESSONS: Duodenum diverticulum is a rare false-positive uptake of I-131, it might be a diagnostic challenge when there are many false-positive uptake of I-131 in evaluation of DTC. So it must be significant to be familiar with these physiologic and pathologic variants of I-131 uptake and make further efforts to accurately interpret radioiodine scintigraphy results.

Hyperbaric Oxygen Attenuates Withdrawal Symptoms by Regulating Monoaminergic Neurotransmitters and NO Signaling Pathway at Nucleus Accumbens in Morphine-Dependent Rats.

In this study, we examined whether hyperbaric oxygen (HBO2) plays a detoxification role in withdrawal symptoms in a morphine-dependent rat model. The model was established through injections of morphine at increasing doses for 7 days. Withdrawal symptoms were induced by naloxone injection on the 8th day. The detoxification effect of HBO2 was evaluated using the withdrawal symptom scores, biochemical indices and neurotransmitters. Compared with the model group, HBO2 therapy significantly attenuated the withdrawal symptom scores, body weight loss and the level of norepinephrine level, whereas it increased the dopamine level and tyrosine hydroxylase expression in the nucleus accumbens. Moreover, HBO2 therapy substantially alleviated the NO, NOS, cAMP, and cGMP levels. Our findings indicate that HBO2 can effectively alleviate withdrawal symptoms induced by morphine dependence, and these effects may be attributed to the modulation of monoaminergic neurotransmitters and the suppression of the NO-cGMP signaling pathway.

Application of postoperative autotransfusion in total joint arthroplasty reduces allogeneic blood requirements: a meta-analysis of randomized controlled trials.

BACKGROUND: Total joint arthroplasty is associated with significant blood loss and often requires blood transfusion. However, allogeneic blood transfusion (ABT) may lead to severe problems, such as immunoreaction and infection. Postoperative autotransfusion, an alternative to ABT, is controversial. We conducted a meta-analysis to evaluate the ability of postoperative autotransfusion to reduce the need for ABT following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Systematic literature searches for randomized controlled trials were performed using PubMed, Embase, and the Cochrane Library until February 2016. Relative risks (RRs) and weighted mean differences with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models; we also evaluated publication bias and heterogeneity. RESULTS: Seventeen trials with a total of 2314 patients were included in the meta-analysis. The pooled RRs of ABT rate between autotransfusion and the regular drainage/no drainage groups for TKA and THA were 0.446 (95% CI = 0.287, 0.693; p < 0.001) and 0.757 (95% CI = 0.599, 0.958; p = 0.020), respectively. In the subgroup analysis performed in TKA patients according to control interventions, the pooled RRs were 0.377 (95% CI = 0.224, 0.634; p < 0.001) (compared with regular drainage) and 0.804 (95% CI = 0.453, 1.426, p = 0.456) (compared with no drainage). In the subgroup analysis performed for THA, the pooled RRs were 0.536 (95% CI = 0.379, 0.757, p < 0.001) (compared with regular drainage) and 1.020 (95% CI = 0.740, 1.405, p = 0.904) (compared with no drainage). CONCLUSIONS: Compared to regular drainage, autotransfusion reduces the need for ABT following TKA and THA. This reduction is not present when comparing autotransfusion to no drainage. However, the reliability of the meta-analytic results concerning TKA was limited by significant heterogeneity in methods among the included studies.