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Total hip arthroplasty (THA) is considered the best treatment for sequelae of suppurative hip arthritis, but such patients are more likely to have occult infection and therefore to suffer post-operative periprosthetic joint infection. Our study examined (1) the occult infection rate among patients with sequelae of suppurative hip arthritis, and whether (2) neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), or fibrinogen levels can be used to screen such patients for occult infection before THA.We retrospectively enrolled 428 patients who underwent primary THA at our hospital between 2010 and 2021, of whom 31 had occult infection and 397 did not. The maximum sensitivity and specificity were determined for the three indicators using receiver operating characteristic curves, and positive and negative predictive values were calculated.Patients with occult infection showed significantly higher erythrocyte sedimentation rate (ESR) and higher levels of C-reactive protein (CRP) and fibrinogen than those without occult infection. The various potential indicators gave the following areas under the receiver operating characteristic curves: ESR, 0.586; CRP, 0.599; interleukin-6, 0.651; NLR, 0.506; MLR, 0.600; and fibrinogen, 0.589. Sensitivity and specificity were as follows: ESR, 30.8% and 92.5%; CRP, 50.0% and 70.2%; interleukin-6, 57.7% and 67.5%; NLR, 46.7% and 62.9%; MLR, 60.0% and 61.7%; and fibrinogen, 43.3% and 81.7%.The rate of occult infection was 7.24% among our patients. ESR, NLR, MLR, and levels of CRP, interleukin-6, and fibrinogen may be unreliable for screening such patients for occult infection before THA according to sensitivity and specificity.

To evaluate the diagnostic values of preoperative plasma fibrinogen and platelet count for screening fixation-related infection (FRI) in patients undergoing conversion total hip arthroplasty (cTHA) after failed internal fixation of hip fractures.This was a single-center retrospective study. Data were retrospectively analyzed for 435 patients who underwent cTHA in our hospital from January 2008 to September 2020. They were divided into infected (n = 30) and non-infected groups (n = 405) according to the 2013 International Consensus Meeting (ICM) criteria. The diagnostic sensitivity and specificity of plasma fibrinogen and platelet count were determined using receiver operating characteristic (ROC) curves. Optimal predictive cutoffs of these two markers were determined based on the Youden index. In addition, the diagnostic value of preoperative serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for screening FRI were also evaluated based on the cutoffs recommended by the 2013 ICM Criteria. Finally, the diagnostic ability of various combinations of the plasma fibrinogen and platelet count as well as serum CRP and ESR was re-assessed.The numbers of patients with and without FRI were 30 (6.9%) and 405 (93.1%), respectively. Areas under the ROC curves were 0.770 for fibrinogen, 0.606 for platelet, 0.844 for CRP and 0.749 for ESR. The optimal predictive cutoff of fibrinogen was 3.73 g/L, which gave sensitivity of 60.0% and specificity of 90.5%. The optimal predictive cutoff for platelet was 241.5 × 10Preoperative serum CRP, ESR, plasma fibrinogen and platelet count have low sensitivity on their own for screening FRI in patients, but the combination of CRP with fibrinogen shows promise for that.

Research question Whether extracellular vesicle-derived lncRNAs could serve as promising circulating biomarkers for endometriosis? Design To obtain novel diagnostic markers, we enrolled 85 patients with endometriosis as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify exosomal long non-coding RNAs (lncRNAs) that are differentially expressed between women with endometriosis (n=5) and unaffected participants (n=6). Messenger RNA and lncRNA sequences of the plasma exosomes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. LncRNA expression levels were further validated using quantitative reverse transcriptase polymerase chain reaction. Moreover, receiver operating characteristic curve analysis was performed to determine the diagnostic value of candidate lncRNAs. Clinical features were correlated to the expression levels of candidate lncRNAs. Results We found that 210 lncRNAs were significantly dysregulated; among these, expression of LINC01569, RP3-399L15.2, FAM138B, and CH507-513H4.6 was significantly decreased, whereas expression of RP11-326N17.2, KLHL7-AS1, and MIR548XHG was increased, in the plasma of patients with endometriosis. Combined expression level of RP3-399L15.2 and CH507-513H4.6 was used to distinguish patients with endometriosis from control participants; the results revealed a sensitivity of 80.00% and specificity of 85.45% at the cutoff point, and an area under the ROC curve of 0.9045. Our findings demonstrated the potential of these two lncRNAs as diagnostic biomarkers for endometriosis. Moreover, CH507-513H4.6 alone may be useful to detect early-stage endometriosis lesions. Conclusions The combination of RP3-399L15.2 and CH507-513H4.6 can be potential candidates for endometriosis biomarkers.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a family of often-concurrent diseases with various anatomical spectra. Null-mutant Gen1 mice frequently develop multiple urinary phenotypes, most commonly duplex kidneys, and are ideal subjects for research on ectopic budding in CAKUT development. The upper and lower kidney poles of the Gen1

The foetus can be regarded as a half‐allograft implanted into the maternal body. In a successful pregnancy, the mother does not reject the foetus because of the immune tolerance mechanism at the maternal‐foetal interface. The innate immune cells are a large part of the decidual leukocytes contributing significantly to a successful pregnancy. Although the contributions have been recognized, their role in human pregnancy has not been completely elucidated. Additionally, the accumulated evidence demonstrates that the immune checkpoint molecules expressed on the immune cells are co‐inhibitory receptors regulating their activation and biological function. Therefore, it is critical to understand the immune microenvironment and explore the function of the innate immune cells during pregnancy. This review summarizes the classic immune checkpoints such as PD‐1, CTLA‐4 and some novel molecules recently identified, including TIM‐3, CD200, TIGIT and the Siglecs family on the decidual and peripheral innate immune cells during pregnancy. Furthermore, it emphasizes the role of the immune checkpoint molecules in pregnancy‐associated complications and reproductive immunotherapy.

Background Although serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and neutrophil–lymphocyte ratio (NLR) are promising biomarkers for screening PJI in patients undergoing revision arthroplasty, their efficacy with respect to re-revision arthroplasty remains unclear. Methods We included patients who underwent re-revision arthroplasty at our hospital during 2008–2020, and stratified them into two groups whether they had been diagnosed with PJI (infected) or aseptic failure (non-infected) according to the 2013 International Consensus Meeting criteria. We evaluated the diagnostic performance of CRP, ESR, fibrinogen and NLR, both individually and in combinations, based on sensitivity, specificity, and area under the receiver operating characteristic curve. Results Of the 63 included patients, 32 were diagnosed with PJI. The area under the ROC curve was 0.821 for CRP, 0.794 for ESR, 0.885 for fibrinogen and 0.702 for NLR. CRP gave a sensitivity of 87.5% and specificity of 74.2% with an optimal predictive cut-off of 8.50 mg/mL. ESR gave a sensitivity of 81.3% and specificity of 71.0% with an optimal predictive cut-off of 33 mm/h. Plasma fibrinogen gave a comparatively higher sensitivity of 93.8% and specificity of 77.4% with an optimal predictive cut-off of 3.55 g/L, while NLR gave a moderate sensitivity of 84.4% but low specificity of 54.8% with an optimal predictive cut-off of 2.30. The combination of fibrinogen and CRP gave a high AUC of 0.897, an acceptable sensitivity of 75% and a high specificity 93.5%. Conclusions Plasma fibrinogen is a cost-effective, convenient biomarker that can be used to rule out PJI in patients scheduled for re-revision arthroplasty. In combination with CRP, it may be effective in diagnosing PJI in such patients.

Skin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR‐411‐3p in bleomycin (BLM)‐induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real‐time quantitative polymerase chain reaction assess the expression levels of miR‐411‐3p, collagen (COLI) and transforming growth factor (TGF)‐β/Smad ubiquitin regulatory factor (Smurf)‐2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR‐411‐3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR‐411‐3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR‐411‐3p expression was decreased in bleomycin (BLM)‐induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)‐β signalling and collagen production. Overexpression of miR‐411‐3p inhibited the expression of collagen, F‐actin and the TGF‐β/Smad signalling pathway factors in BLM‐induced skin fibrosis and fibroblasts. In addition, miR‐411‐3p inhibited the target Smad ubiquitin regulatory factor (Smurf)‐2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF‐β/Smad signalling pathway. We demonstrated that miR‐411‐3p exerts antifibrotic effects by inhibiting the TGF‐β/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.

Background The preoperative diagnosis of periprosthetic joint infection (PJI) in patients undergoing re-revision arthroplasty is crucial, so we evaluated whether plasma levels of D-dimer and fibrin degradation product (FDP) could aid such diagnosis. Methods We retrospectively analyzed data on patients who underwent re-revision hip or knee arthroplasty at our institute during 2008–2020. Patients were stratified into those who experienced PJI or not, based on 2013 International Consensus Meeting Criteria. Plasma levels of D-dimer and FDP as well as levels of the traditional inflammatory biomarkers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin-6 were compared between the groups. The ability of these biomarkers to diagnose PJI was assessed based on the area under the receiver operating characteristic (AUC) curve, for which predictive cut-offs were optimized based on the Youden index. Results Based on a cut-off of 0.80 mg/L, D-dimer gave an AUC of 0.595, high sensitivity of 85.7% but poor specificity of 47.8%. Based on a cut-off of 2.80 mg/L, FDP gave an AUC of 0.550, poor sensitivity of 56.5% and poor specificity of 52.9%. CRP, ESR and interleukin-6 showed much better diagnostic ability, with AUCs > 0.82. The combination of CRP and interleukin-6 gave an AUC of 0.877, high sensitivity of 91.7% and acceptable specificity of 78.3%. Conclusions Plasma levels of D-dimer and FDP may be inappropriate for diagnosing PJI in patients undergoing re-revision arthroplasty, whereas the combination of serum CRP and interleukin-6 may be effective.

Background Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. Methods We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. Results All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001). Conclusions Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.

IntroductionSeveral studies have evaluated the diagnostic values of D-dimer and fibrin degradation product (FDP) for detecting periprosthetic joint infection (PJI), but their conclusions have been inconsistent. More importantly, whether the diagnostic value of these two biomarkers differs depending on whether they are assayed in plasma or serum is unclear.Methods and analysisThis prospective single-centre, parallel comparative study will involve patients planning to undergo revision hip or knee arthroplasty due to an aseptic mechanical failure or PJI. After the patients provide written informed consent, their serum and plasma will be sampled and assayed for D-dimer and FDP. The diagnostic value of these two biomarkers in plasma and serum will be compared with one another and with the value of two traditional inflammatory markers (C reactive protein and erythrocyte sedimentation rate) used to diagnose PJI according to the 2013 International Consensus Meeting criteria. Diagnostic value will be assessed in terms of area under receiver operating characteristic curves, sensitivity, specificity, as well as positive and negative predictive values, all calculated based on the optimal cut-off determined from the Youden index.Ethics and disseminationThis study was approved by the Ethics Committee of our hospital (approval no. 2020-859). Written informed consent will be obtained from all patients before enrollment. Study findings will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038547), and it is ongoing.Title