Application of Medical Statistical and Machine Learning Methods in the Age Estimation of Living Individuals.

In the study of age estimation in living individuals, a lot of data needs to be analyzed by mathematical statistics, and reasonable medical statistical methods play an important role in data design and analysis. The selection of accurate and appropriate statistical methods is one of the key factors affecting the quality of research results. This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics, difference analysis, consistency test and multivariate statistical analysis, as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals, and summarizes the relevance and application prospects between medical statistical methods and machine learning methods. This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.

Diamond with Sp2-Sp3 composite phase for thermometry at Millikelvin temperatures.

Temperature is one of the seven fundamental physical quantities. The ability to measure temperatures approaching absolute zero has driven numerous advances in low-temperature physics and quantum physics. Currently, millikelvin temperatures and below are measured through the characterization of a certain thermal state of the system as there is no traditional thermometer capable of measuring temperatures at such low levels. In this study, we develop a kind of diamond with sp2-sp3 composite phase to tackle this problem. The synthesized composite phase diamond (CPD) exhibits a negative temperature coefficient, providing an excellent fit across a broad temperature range, and reaching a temperature measurement limit of 1 mK. Additionally, the CPD demonstrates low magnetic field sensitivity and excellent thermal stability, and can be fabricated into probes down to 1 micron in diameter, making it a promising candidate for the manufacture of next-generation cryogenic temperature sensors. This development is significant for the low-temperature physics researches, and can help facilitate the transition of quantum computing, quantum simulation, and other related technologies from research to practical applications.

Janus structure hydrogels: recent advances in synthetic strategies, biomedical microstructure and (bio)applications.

Janus structure hydrogels (JSHs) are novel materials. Their primary fabrication methods and various applications have been widely reported. JSHs are primarily composed of Janus particles (JNPs) and polysaccharide components. They exhibit two distinct physical or chemical properties, generating intriguing characteristics due to their asymmetric structure. Normally, one side (adhesive interface) is predominantly constituted of polysaccharide components, primarily serving excellent adhesion. On the other side (functional surface), they integrate diverse functionalities, concurrently performing a plethora of synergistic functions. In the biomedical field, JSHs are widely applied in anti-adhesion, drug delivery, wound healing, and other areas. It also exhibits functions in seawater desalination and motion sensing. Thus, JSHs hold broad prospects for applications, and they possess significant research value in nanotechnology, environmental science, healthcare, and other fields. Additionally, this article proposes the challenges and future work facing these fields.

Machine-learning models for diagnosis of rotator cuff tears in osteoporosis patients based on anteroposterior X-rays of the shoulder joint.

OBJECTIVE: This study aims to diagnose Rotator Cuff Tears (RCT) and classify the severity of RCT in patients with Osteoporosis (OP) through the analysis of shoulder joint anteroposterior (AP) X-ray-based localized proximal humeral bone mineral density (BMD) measurements and clinical information based on machine learning (ML) models. METHODS: A retrospective cohort of 89 patients was analyzed, including 63 with both OP and RCT (OPRCT) and 26 with OP only. The study analyzed a series of shoulder radiographs from April 2021 to April 2023. Grayscale values were measured after plotting ROIs based on AP X-rays of shoulder joint. Five kinds of ML models were developed and compared based on their performance in predicting the occurrence and severity of RCT from ROIs' greyscale values and clinical information (age, gender, advantage side, lumbar BMD, and acromion morphology (AM)). Further analysis using SHAP values illustrated the significant impact of selected features on model predictions. RESULTS: R1-6 had a positive correlation with BMD respectively. The nine variables, including greyscale R1-6, age, BMD, and AM, were used in the prediction models. The RF model was determined to be superior in effectively diagnosing RCT in OP patients, with high AUC scores of 0.998, 0.889, and 0.95 in the training, validation, and testing sets, respectively. SHAP values revealed that the most influential factors on the diagnostic outcomes were the grayscale values of all cancellous bones in ROIs. A column-line graph prediction model based on nine variables was constructed, and DCA curves indicated that RCT prediction in OP patients was favored based on this model. Furthermore, the RF model was also the most superior in predicting the types of RCT within the OPRCT group, with an accuracy of 86.364% and 73.684% in the training and test sets, respectively. SHAP values indicated that the most significant factor affecting the predictive outcomes was the AM, followed by the grayscale values of the greater tubercle, among others. CONCLUSIONS: ML models, particularly the RF algorithm, show significant promise in diagnosing RCT occurrence and severity in OP patients using conventional shoulder X-rays based on the nine variables. This method presents a cost-effective, accessible, and non-invasive diagnostic strategy that has the potential to substantially enhance the early detection and management of RCT in OP patient population.

Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Exploration of the molecular mechanism guiding Xinfeng capsule regulatory mechanism for rheumatoid arthritis inflammation.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joint synovium. The traditional Chinese medicine Xinfeng capsule (XFC) has a remarkable alleviating effect on inflammatory symptoms, such as joint pain and swelling, in patients with RA. However, the underlying mechanism of action remains to be elucidated. This study intended to conduct network pharmacology, animal experiments, data mining, and molecular docking to explore the molecular mechanism through which XFC can improve the inflammatory symptoms of RA. METHODS: The Apriori association rules and a random walk model were employed to evaluate the effect of XFC on the clinical inflammatory indexes of RA. The active ingredients and the potential target genes of XFC were obtained from public databases. Based on the search tool for recurring instances of neighboring genes (STRING) database, the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, Cytoscape software, and molecular docking method, the molecular mechanism by which XFC acts on RA was also analyzed. Finally, an adjuvant arthritis rat model was established to verify the effects of XFC on inflammation-related signaling pathways and inflammatory factors. RESULTS: XFC significantly reduced the level of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and the erythrocyte sedimentation rate (ESR). The docking space structures of the active ingredients in XFC, namely triptolide and quercetin, and the key targets were stable. Inflammation-related biological processes were identified as the key factors involved in the development of RA, and the regulation of the toll-like receptor (TLR) signaling pathway may be the key link for XFC toward improving the inflammatory state of RA. The expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), TGF-beta-activated kinase 1 (TAK1), phospho-Inhibitor of NF-κB kinaseß (p-IKKß), phospho-Nuclear factor-k-gene binding (p-NF-κB), and interleukin-1ß (IL-1ß) can all be decreased by XFC. XFC improves joint inflammation symptoms by lowering pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (INF-γ) levels. CONCLUSIONS: XFC could effectively improve the clinical inflammatory indexes of RA. The active ingredients of XFC improved the inflammatory state of RA by regulating the TLR-signaling pathway.

Identification of a molecular network regulated by multiple ASD high risk genes.

Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling. Common gene targets of these ASD risk genes include a network of high confidence ASD genes associated with gene expression regulation, such as CTNNB1 and SMARCA4. We further directly examined the transcriptional impact of the deficiency of these ASD risk genes. Our mRNA profiling with qPCR assays in cells with the knockdown of Adnp, Kdm6b, Chd2 or Med13 has revealed an intricate pattern of their cross-regulation, as well as their influence on the expression of other ASD genes. In addition, some synaptic genes, such as Snap25 and Nrxn1, are strongly regulated by deficiency of the four ASD risk genes, which could be through the direct binding at promoters or indirectly through the targets like Ctnnb1 or Smarca4. The identification of convergent and divergent gene targets that are regulated by multiple ASD risk genes will help to understand the molecular mechanisms underlying common and unique phenotypes associated with haploinsufficiency of ASD-associated genes.

Unveiling the effect of the structural transformation of CoZn-MOF on BiVO4 photoanode for efficient photoelectrochemical water oxidation.

Photoelectrochemical (PEC) water splitting has been widely investigated for solar-to-hydrogen conversion. However, issues like high charge recombination rate and slow surface water oxidation kinetics severely hinder its (PEC) conversion efficiency. Herein, we constructed MOF-derived CoOOH cocatalyst on BiVO4 photoanode, using a feasible electrochemical activation strategy. The BiVO4-based photoanode obtained shows a high photocurrent density of 3.15 mA/cm2 at 1.23 VRHE and low onset potential. Detailed experiments and theoretical calculations show that during the activation of CoZn-MOFs, there was a partial breakage of 2-methylimidazole (mIM) linker, an increase in the oxidation state of Cobalt ion (Co), and increased O2-. The high PEC performance is mainly attributed to the MOF-derived CoOOH, which provides rich active sites for hole extraction and reduces the overpotential for oxygen evolution reaction. Furthermore, when CoZnNiFe-LDHs were decorated on BiVO4 using the ions exchange method, the photocurrent density of BiVO4/CoZnNiFe-LDHs photoanode got to 4.0 mA/cm2 at 1.23 VRHE, accompanied with high stability. This study provides insights into understanding the key role played by the structural transformation of MOF cocatalyst in PEC water splitting processes.

Ultra-compact acousto-optic modulation using on-chip integrated Bragg gratings on lithium niobate-chalcogenide hybrid platform.

An ultra-compact and efficient acousto-optic modulator based on a thin-film lithium niobate-chalcogenide (ChG) hybrid platform was designed and realized. In this approach, π phase-shift Bragg grating has an ultra-short effective interaction length of only ∼ 300 µm and a compact footprint of 200 × 300 µm2. The strong microwave-acoustic coupling and superior photo-elastic property of the ChG allow us to achieve a half-wave voltage of Vπ = 1.08 V (4.07 V) for the π phase-shift Bragg grating (waveguide Bragg grating), corresponding to VπL = 0.03 V·cm (0.09 V·cm). This acousto-optic modulator exhibits a compact size, and low power consumption, and can be used for on-chip optical interconnects and microwave photonics.

Identification and immunological role of cuproptosis in osteoporosis.

Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity.

Accelerating Antimicrobial Peptide Discovery for WHO Priority Pathogens through Predictive and Interpretable Machine Learning Models.

The escalating menace of multidrug-resistant (MDR) pathogens necessitates a paradigm shift from conventional antibiotics to innovative alternatives. Antimicrobial peptides (AMPs) emerge as a compelling contender in this arena. Employing in silico methodologies, we can usher in a new era of AMP discovery, streamlining the identification process from vast candidate sequences, thereby optimizing laboratory screening expenditures. Here, we unveil cutting-edge machine learning (ML) models that are both predictive and interpretable, tailored for the identification of potent AMPs targeting World Health Organization's (WHO) high-priority pathogens. Furthermore, we have developed ML models that consider the hemolysis of human erythrocytes, emphasizing their therapeutic potential. Anchored in the nuanced physical-chemical attributes gleaned from the three-dimensional (3D) helical conformations of AMPs, our optimized models have demonstrated commendable performance-boasting an accuracy exceeding 75% when evaluated against both low-sequence-identified peptides and recently unveiled AMPs. As a testament to their efficacy, we deployed these models to prioritize peptide sequences stemming from PEM-2 and subsequently probed the bioactivity of our algorithm-predicted peptides vis-à-vis WHO's priority pathogens. Intriguingly, several of these new AMPs outperformed the native PEM-2 in their antimicrobial prowess, thereby underscoring the robustness of our modeling approach. To elucidate ML model outcomes, we probe via Shapley Additive exPlanations (SHAP) values, uncovering intricate mechanisms guiding diverse actions against bacteria. Our state-of-the-art predictive models expedite the design of new AMPs, offering a robust countermeasure to antibiotic resistance. Our prediction tool is available to the public at https://ai-meta.chem.ncu.edu.tw/amp-meta.

Targeted inhibition of gut bacterial ß-glucuronidases by octyl gallate alleviates mycophenolate mofetil-induced gastrointestinal toxicity.

Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated ß-glucuronidase (ßGUS). Therefore, controlling microbiota-produced ßGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.

TEDOFA Trial Study Protocol: A Prospective Double-Blind, Randomized, Controlled Clinical Trial Comparing Opioid-Free versus Opioid Anesthesia on the Quality of Postoperative Recovery and Chronic Pain in Patients Receiving Thoracoscopic Surgery.

Introduction: Seeking effective multimodal analgesia and anesthetic regimen is the basis for the success of ERAS. Opioid-free anesthesia (OFA) is a multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and α-2 agonists. Although previous studies have confirmed that OFA is safe and feasible for VATS surgery, there is great heterogeneity in how to select and combine anti-harm drugs to replace opioids. We hypothesized that the reduced opioid use during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events and an improvement in the quality of rehabilitation of patients after partial VATS lung resection. Methods/Analysis: The TEDOFA Study is a prospective double-blind, randomized, controlled clinical trial with a concealed allocation of patients scheduled to undergo elective partial VATS pneumonectomy 1:1 to receive either a standard anesthesia protocol or an OFA. A total of 146 patients were recruited in the study. Primary endpoint was the 15-item recovery quality scale (QoR-15) at 24 hours after surgery. Ethics and Dissemination: This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. The TEDOFA trial study protocol was approved on 27 February 2023. The trial started recruiting patients after registered on the Chinese Clinical Trial Registry. Trial Registration Number: ChiCTR2300069210; Pre-results.

The role of transforming growth factor beta in myopia development.

Myopia is widely recognized as an epidemic. Studies have found a link between Transforming Growth Factor-beta (TGF-ß) and myopia, but the specific molecular mechanisms are not fully understood. In this study, a monocular model in tree shrews (Tupaia belangeri) was established to verify the molecular mechanism of TGF-ß in myopia. The results indicated that there were significant changes in TGF-ßs during the treatment of myopia, which could enhance the refractive ability and axial length of the eye. Immunohistochemical staining, real-time fluorescent quantitative PCR, and immunoblotting results showed a significant upregulation of MMP2 and NF-κB levels, and a significant downregulation of COL-I expression in the TGF-ß treated eyes, suggesting that NF-κB and MMP2 are involved in the signaling pathways of TGF-ßs induced myopia and axial elongation. Moreover, the expression levels of IL-6, IL-8, MCP-1, IL-1ß, TNF-α, TAK1, and NF-κB in the retina were all significantly elevated. This indicates that TGF-ß stimulates the inflammatory response of retinal pigment epithelial cells through the TAK1-NF-κB signaling pathway. In conclusion, this study suggests that TGF-ß promotes the progression of myopia by enhancing intraocular inflammation.

LONG-TERM OUTCOME OF TRANSSCLERAL FOUR-POINT FIXATION OF AKREOS INTRAOCULAR LENS WITH CLOSED CONTINUOUS-LOOP SUTURE.

PURPOSE: To report the long-term clinical outcomes of transscleral four-point fixation of Akreos intraocular lens using a closed continuous-loop suture technique. METHODS: This was a retrospective, multicenter, interventional case series. Primary outcome measures were best-corrected visual acuity, intraocular pressure, corneal endothelial cell density, and complications with a minimum of 1-year follow-up. RESULTS: One hundred and ninety-two eyes of 177 patients from two surgical hospital sites were identified. The mean best-corrected visual acuity improved from 0.88 ± 0.74 logarithm of the minimum angle of resolution (Snellen 20/152) preoperatively to 0.42 ± 0.52 logarithm of the minimum angle of resolution (Snellen 20/53) postoperatively ( P < 0.001). The mean preoperative intraocular pressure was 17.51 ± 8.67 mmHg, and the mean postoperative intraocular pressure at final follow-up was 15.08 ± 4.18 mmHg ( P = 0.001). The mean corneal endothelial cell density significantly reduced from 2,259 ± 729 cells/mm 2 to 2077 ± 659 cells/mm 2 , representing a cell loss of 5.73% ( P < 0.001). The intraocular lens was fixed well during follow-up. There were no intraoperative complications noted. Postoperative complications included transient ocular hypertension in 15 eyes (7.81%), hypotony in two eyes (1.04%), retinal detachment in one eye (0.52%), and macular edema in one eye (0.52%). CONCLUSION: The transscleral four-point fixation Akreos intraocular lens using the closed continuous-loop suture technique was effective and safe with satisfactory visual acuity with a minimum of 1-year follow-up.

[Circular RNA Cbl proto-oncogene B (circCBLB) inhibits proliferation, promotes apoptosis, and increases anti-inflammatory cytokine levels of fibroblast-like synoviocytes in rheumatoid arthritis].

Objective To explore the regulatory axis of circular RNA Cbl proto-oncogene B (circCBLB)/miR-486-5p on the proliferation, apoptosis, and inflammatory cytokines of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS). Methods Human RA-FLS were stimulated with 100 µL of 10 ng/mL of tumor necrosis factor-alpha (TNF-α) to establish the model. The binding relationship of circCBLB/miR-486-5p was validated by a dual-luciferase reporter gene assay. pcDNA3.1/siRNA-circCBLB, negative control (pcDNA3.1-NC/si-NC), and miR-486-5p-mimics were created and transfected into RA-FLS, respectively. The experiment was divided into seven groups: control, TNF-α-treated RA-FLS, pcDNA3.1-circCBLB, pcDNA3.1-NC, si-circCBLB, si-NC, and pcDNA3.1-circCBLB combined with miR-486-5p-mimics. Cell viability was assessed by a CCK-8 assay; cell cycle and apoptosis by flow cytometry; colony formation ability by a colony formation assay; and the expression levels of circCBLB and miR-486-5p by real-time quantitative PCR. The levels of interleukin 4 (IL-4), IL-10, IL-6 and TNF-α were measured by ELISA. Results The dual-luciferase reporter gene assay showed that circCBLB bound to the 3' untranslated region (3'UTR) of miR-486-5p. Compared with the model group at the same time point, the cell viability of the overexpression group was lower, while that of the interference group was higher. Compared with the model group, the overexpression group had a higher apoptosis rate, a higher proportion in S and G2 phases, a lower colony formation rate, a lower miR-486-5p expression level, higher IL-4 and IL-10 levels, and lower IL-6 and TNF-α levels. The interference group had a lower apoptosis rate, a lower proportion in S and G2 phases, a higher colony formation rate, a higher miR-486-5p expression level, and a higher TNF-α level. The pcDNA3.1-circCBLB combined with miR-486-5p-mimics group reversed the effects of circCBLB on cell viability, apoptosis rate, cell cycle, colony formation ability, antiinflammatory cytokines, and proinflammatory cytokines. Conclusion circCBLB inhibits the viability of RA-FLS, increases apoptosis rate, prolongs the cell cycle, reduces colony formation ability, increases antiinflammatory cytokines, and decreases proinflammatory cytokines. In contrast, miR-486-5p has opposite regulatory effects on circCBLB and can partially reverse and offset the effects of circCBLB.

The effect of long-term traditional Chinese medicine treatment on extra-articular lesions of rheumatoid arthritis patients based on propensity score matching: A retrospective cohort study.

Objective: To explore the efficacy of long-term traditional Chinese medicine (TCM) treatment on the occurrence of extra-articular lesions in rheumatoid arthritis (RA) patients. Methods: Our retrospective cohort study included patients diagnosed with RA between January 2018 to December 2019. Patients were divided into TCM treatment group and control group according to whether they received TCM treatment for more than three months. Propensity score matching (PSM) was used to balance covariates between groups. The occurrence time of extra-articular lesions, including interstitial lung disease, Sjögren's syndrome, and anemia, was calculated for both groups after PSM. Additionally, clinical indicators that may affect the occurrence of extra-articular lesions in RA were included in Cox multivariate regression analysis to explore prognostic factors related to RA. Results: A total of 883 RA patients were initially included in our study, with 481 in the TCM treatment group and 279 in the control group. TCM treatment improved all clinical indicators of RA patients, and there was a higher degree of support, confidence, and lift between TCM treatment and the improvement of clinical indicators. There was no significant difference in the rate of extra-articular lesions occurrence between the two groups. After PSM, the median occurrence time of interstitial lung disease, Sjögren's syndrome and anemia in the TCM treatment group were 30.767, 21.370 and 31.970 months, respectively. While in the control group, it was 15.911, 14.667 and 11.825 months, respectively. Cox multivariate regression analysis indicated that TCM treatment was a protective factor for the occurrence of extra-articular lesions in RA, while abnormally high level of IgG was an independent factor for interstitial lung disease and C4 was an independent factor for Sjögren's syndrome. Moreover, a longer duration of TCM usage was associated with a later occurrence of extra-articular lesions. Conclusion: Long-term TCM treatment not only positively affects the occurrence time of extra-articular lesions in RA patients, but also helps reduce the risk of extra-articular lesions occurrence. TCM can be applied flexibly throughout the treatment process for RA patients.

Mediastinal Cryobiopsy for Pathological Diagnosis of Fibrosing Mediastinitis-Associated Pulmonary Hypertension.

INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.