Immune-related osteoblastic bone alterations mimicking bone metastasis in a small-cell lung cancer patient treated with durvalumab: a case report.

Background: Chemotherapy combined with immunotherapy is currently the standard first-line treatment for advanced small-cell lung cancer (SCLC). Immunotherapy can induce specific adverse events, called immune-related adverse events (irAEs). IrAEs of bones have rarely been reported. However, identifying bone irAEs could be important in avoiding misdiagnosis and ensuring appropriate patient management. This is the first report describing the diagnosis of irAEs of osteoblastic bone changes mimicking bone metastasis in a SCLC patient treated with durvalumab. Case Description: In this report, we describe a unique and challenging case in which a 54-year-old female patient with SCLC treated with durvalumab, an immunotherapy drug, exhibited osteoblastic bone changes that appeared similar to bone metastasis on imaging but were actually a side effect of immunotherapy. Before treatment, imaging revealed no bone metastasis. In the third month after treatment with durvalumab, computed tomography (CT) revealed multiple bone alterations, predominantly osteoblastic lesions with minor osteolytic changes. Various imaging tests suggested bone metastasis, but she had no symptoms related to bone disease. Notably, the lesions in the chest had achieved a partial response. Based on a comprehensive analysis of the CT-guided pathological biopsy results, the patient's symptoms, and the biological characteristics of SCLC, we determined that these bone changes were irAEs occurring in the skeletal system. The patient was followed up for 10 months, during which time the bone lesions remained stable. Conclusions: IrAEs of bones are rare, and their manifestations vary. Sometimes, the imaging manifestations of bone irAEs are difficult to distinguish from bone metastasis. If patients show variable treatment responses between different lesions, careful evaluation (including a pathological biopsy) is necessary.

Analysis of virtual standardized patients for assessing clinical fundamental skills of medical students: a prospective study.

BACKGROUND: History-taking is an essential clinical competency for qualified doctors. The limitations of the standardized patient (SP) in taking history can be addressed by the virtual standardized patient (VSP). This paper investigates the accuracy of virtual standardized patient simulators and evaluates the applicability of the improved system's accuracy for diagnostic teaching support and performance assessment. METHODS: Data from the application of VSP to medical residents and students were gathered for this prospective study. In a human-machine collaboration mode, students completed exams involving taking SP histories while VSP provided real-time scoring. Every participant had VSP and SP scores. Lastly, using the voice and text records as a guide, the technicians will adjust the system's intention recognition accuracy and speech recognition accuracy. RESULTS: The research revealed significant differences in scoring across several iterations of VSP and SP (p < 0.001). Across various clinical cases, there were differences in application accuracy for different versions of VSP (p < 0.001). Among training groups, the diarrhea case showed significant differences in speech recognition accuracy (Z = -2.719, p = 0.007) and intent recognition accuracy (Z = -2.406, p = 0.016). Scoring and intent recognition accuracy improved significantly after system upgrades. CONCLUSION: VSP has a comprehensive and detailed scoring system and demonstrates good scoring accuracy, which can be a valuable tool for history-taking training.

Analysis of the epidemiological characteristics and influencing factors of tuberculosis among students in a large province of China, 2008-2018.

This study examines tuberculosis (TB) incidence among students in Jilin Province, China, focusing on spatial, temporal, and demographic dynamics in areas of social inequality. Variation in incidence rate of TB was analyzed using the joinpoint regression method. Spatial analyses techniques included the global and local Moran indices and Getis-Ord Gi* analysis. Demographic changes in new cases were analyzed descriptively, and the Geodetector method measured the influence of risk factors on student TB incidence. The analysis revealed a declining trend in TB cases, particularly among male students. TB incidence showed geographical heterogeneity, with lower rates in underdeveloped rural areas compared to urban regions. Significant spatial correlations were observed, with high-high clusters forming in central Jilin Province. Hotspots of student TB transmission were primarily concentrated in the southwestern and central regions from 2008 to 2018. Socio-economic factors exhibited nonlinear enhancement effects on incidence rates, with a dominant bifactor effect. High-risk zones were predominantly located in urban centers, with university and high school students showing higher incidences than other educational stages. The study revealed economic determinants as being especially important in affecting TB incidence among students, with these factors having nonlinear interacting effects on student TB incidence.

FMT rescues mice from DSS-induced colitis in a STING-dependent manner.

Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.

Focusing on non-responders to infliximab with ulcerative colitis, what can we do first and next?

BACKGROUND: Ulcerative colitis (UC) is a chronic immune-mediated inflammation of the colorectum, for which infliximab (IFX) is currently the mainstay of treatment. However, one-third of patients with UC still fail to benefit from the IFX therapy, and early exposure to IFX impairs the efficacy of other subsequent biologics. Therefore, personalized therapeutic system is urgently needed to assist in clinical decision-making and precision treatment. METHODS: Four microarray datasets of colonic biopsies from UC patients treated with IFX were obtained from the GEO database to form the Training Cohort and Validation Cohort. Differentially expressed genes (DEGs) in Training Cohort were identified and enriched for GO, KEGG and immune cell infiltration analysis. A prediction model for IFX efficacy was developed based on the LASSO and Logistic regression. The predictive accuracy of the model was verified by the Validation Cohort, and the model-genes/proteins were validated by immunohistochemistry. Gene-drug, gene-ncRNA interaction analysis were performed to identify drugs or non-coding RNAs (ncRNAs) that potentially interacted with the model-genes. Homology Modeling and Molecular Docking were conducted to filter the optimal candidate as the subsequent adjuvant or alternative for IFX in predicted non-responders. At last, the down-regulation of the key model-gene/protein CYP24A1 by the drug candidate Deferasirox was verified by Western Blot and qRT-PCR Assay based on cellular experiments. RESULTS: A total of 113 DEGs were identified in the Training Cohort, mainly enriched in inflammatory cell chemotaxis, migration, and response to molecules derived from intestinal microbiota. Activated pro-inflammatory innate immune cells, including neutrophils, M1 macrophages, activated dendritic cells and mast cells, were significantly enriched in colons of non-responders. The prediction model based on three model-genes (IFI44L, CYP24A1, and RGS1) exhibited strong predictive efficacy, with AUC values of 0.901 and 0.80 in the Training and Validation Cohorts, respectively. Higher expression of the three model-genes/proteins in colons of non-responders to IFX was confirmed by clinical colonic mucosal biopsies. 4 Drugs (Calcitriol, Lunacalcipol, Deferasirox, Telaprevir), 15 miRNAs and 66 corresponding lnRNAs interacting with model-genes were identified. The protein 3D structure of the key model-gene/protein (human-derived CYP24A1) was developed. Through the Molecular Docking and cellular experimental validation, Deferasirox, which significantly down-regulated both the RNA and protein expression of CYP24A1, was identified as the optimal adjuvant or alternative for IFX in predicted non-responders with UC. CONCLUSION: This study developed a novel prediction model for pre-assessing the efficacy of IFX in patients with UC, as the first step towards personalized therapy. Meanwhile, drugs and non-coding RNAs were provided as potential candidates to develop the next-step precise treatment for the predicted non-responders. In particular, Defeasirox appears to hold promise as an adjuvant or alternative to IFX for the optimization of UC therapy.

Impact of Pulmonary microbiota on lung cancer treatment-related pneumonia.

Background: The use of immunotherapy is progressively expanding for the treatment of lung cancer, either alone or in combination with radiotherapy. However, treatment-related adverse events, especially pneumonia, significantly limit the drug's effectiveness in treating lung cancer. The occurrence of lung cancer, immunotherapy, and pulmonary radiotherapy can all contribute to the imbalance in the pulmonary microbiota, rendering the lungs more susceptible to inflammatory reactions. Methods: Mouse models of lung transplantation tumor were treated with either PD-1 monoclonal antibody or radiotherapy alone, or in combination. The differences in lung inflammation among the different treatment groups were regularly observed by micro-CT. Further, bronchoalveolar lavage fluid was extracted for macrogenomic and cytokine detection. The transcriptional genome of tumor-filled lung tissue was also sequenced. Results: When treated with a combination of PD-1 and radiotherapy, the CT scans showed more severe pulmonary inflammation. However, with the addition of continuously administered antibiotics, no exacerbation of pneumonia signs was observed. Moreover, the differential gene expression and cytokine profiles in the combination treatment group differed from those in the PD-1 monotherapy group and the radiotherapy monotherapy group. This discrepancy does not seem to be a straightforward superimposition of radiation-induced pneumonia and immune-related pneumonia. Further exploration of changes in pulmonary microbiota revealed specific bacterial interactions with DEGs and cytokines. Conclusions: The underlying causes of this susceptibility are intricate and may be associated with the complexity of pulmonary microbiota imbalance, along with fluctuations in the abundance of specific microbiota species.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

Atorvastatin ameliorated myocardial fibrosis by inhibiting oxidative stress and modulating macrophage polarization in diabetic cardiomyopathy.

In this editorial, we commented on the article published in the recent issue of the World Journal of Diabetes. Diabetic cardiomyopathy (DCM) is characterized by myocardial fibrosis, ventricular hypertrophy and diastolic dysfunction in diabetic patients, which can cause heart failure and threaten the life of patients. The pathogenesis of DCM has not been fully clarified, and it may involve oxidative stress, inflammatory stimulation, apoptosis, and autophagy. There is lack of effective therapies for DCM in the clinical practice. Statins have been widely used in the clinical practice for years mainly to reduce cholesterol and stabilize arterial plaques, and exhibit definite cardiovascular protective effects. Studies have shown that statins also have anti-inflammatory and antioxidant effects. We were particularly concerned about the recent findings that atorvastatin alleviated myocardial fibrosis in db/db mice by regulating the antioxidant stress and anti-inflammatory effects of macrophage polarization on diabetic myocardium, and thereby improving DCM.

JAK inhibitors attenuate hyperactivation of nonswitched memory B cells in rheumatoid arthritis patients in remission.

OBJECTIVE: To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission. METHODS: Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry. RESULTS: Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased. CONCLUSION: RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.

Peripheral Th17/Treg imbalance in Chinese patients with untreated antisynthetase syndrome associated interstitial lung disease.

Interstitial lung disease (ILD) is a common and fatal manifestation of antisynthetase syndrome (ASS). The aim of this study was to provide new insight into investigate peripheral blood lymphocytes, CD4+ T cells, cytokine levels and their relation to the clinical profile of untreated patients with ASS-ILD. The retrospective study population included thirty patients diagnosed with ASS-ILD and 30 healthy controls (HCs). Baseline clinical and laboratory data were collected for all subjects, including peripheral blood lymphocyte, CD4+ T cell subsets measured by flow cytometry, and serum cytokine levels measured by multiple microsphere flow immunofluorescence. Their correlations with clinical and laboratory findings were analyzed by Pearson's or Spearman's correlation analysis. In addition, the Benjamini-Hochberg method was used for multiple correction to adjust the p-values. Patients with ASS-ILD had lower CD8+ T cells, higher proportion of Th17 cells and Th17/Treg ratio than HCs. Serum cytokine levels (IL-1ß, IL-6, IL-12, IL-17, IL-8, IL-2, IL-4, IL-10, TNF-α and IFN-γ) were higher in patients with ASS-ILD than HCs. Moreover, Th17/Treg ratio was negatively correlated with diffusing capacity of carbon monoxide (DLCO)%. Our study demonstrated abnormalities of immune disturbances in patients with ASS-ILD, characterized by decreased CD8+ T cells and an increased Th17/Treg ratio, due to an increase in the Th17 cells. These abnormalities may be the immunological mechanism underlying the development of ILD in ASS.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Unveiling the mechanism of source-sink rebalancing in cucumber-pumpkin heterografts: the buffering roles of rootstock cotyledon.

Grafting onto pumpkin rootstock is widely applied in cucumber production to improve growth and yield, as well as to overcome soil-borne diseases and enhance resistance to abiotic stresses. In this study, we constructed the cucumber-pumpkin heterografts with the one-cotyledon grafting method, and examined the effects of heterografting on biomass allocation and sugar partitioning, with cucumber and pumpkin self-grafts used as control. Compared with cucumber self-grafts, heterografting onto pumpkin rootstock promoted photosynthesis in cucumber scion, and led to higher sucrose contents in the 1st true leaf (source) and newly emerged leaf (sink). Thereby, the scion part of heterografts accumulated more biomass than cucumber self-grafts. In contrast, when compared to pumpkin self-grafts, grafting with cucumber scion reduced root vigor and biomass but promoted cotyledon growth in pumpkin rootstock. The roots (sink) of heterografts contained less sucrose and hexoses, and showed reduced sucrose synthase (SuSy) and hexokinase (HXK) activities. However, the rootstock cotyledon (source) contained more sucrose and starch, and showed higher activities of HXK, cell-wall invertase (CWIN), and enzymes for starch synthesis and degradation. Furthermore, removal or shade of rootstock cotyledon led to reduced growth of root and scion. Silencing of CmoMEX1a gene in rootstock cotyledon inhibited maltose export and reduced root growth of heterografts. These results indicated that rootstock cotyledon, especially its starch content, played a buffering role in the growth regulation of cucumber-pumpkin heterografts. Taken together, our results provided a major contribution to our understanding of source-sink sugar partitioning and scion-rootstock growth balancing in cucumber-pumpkin heterografts.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

OBJECTIVE: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. METHODS: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. RESULTS: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. CONCLUSION: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

Real-world incidence and risk factors of pneumonitis in chemoradiation plus immune checkpoint inhibitors compared with chemoradiation alone in lung cancer: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have shown high efficacy in lung cancer. Adding ICIs to chemoradiation might increase the treatment efficacy, while the application of ICIs or chemoradiation alone can induce treatment-related pneumonitis, so whether combination therapy would increase the risk of pneumonitis needs careful evaluation. This study aimed to retrospectively analyze the incidence of pneumonitis in patients who underwent chemoradiation combined with ICIs compared with chemoradiation alone and explore the risk factors of pneumonitis in combination therapy. Methods: This was a retrospective cohort study. Patients who received conventional thoracic radiation with a minimum total dose of 50 Gy for lung cancer between January 2020 and December 2021 at West China Hospital were retrospectively reviewed and followed up for at least 6 months after radiation. Patients were divided into two groups according to whether chemoradiation was administered with or without ICIs. Pneumonitis was evaluated by chest computed tomography (CT) at least every 2 months in outpatient department. The clinical characteristics, including sex, age, smoking history, pathological diagnosis, baseline pulmonary disease [including chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD)], treatment strategy, location of primary tumor and radiological dosimetric parameters were recorded. Chi-squared tests or Fisher's exact tests were performed to analyze the difference between the combination group and control group for categorical variables and Mann-Whitney U test for continuous variables. Univariate and multivariate analyses were performed by logistic regression. Results: A total of 152 patients who received chemoradiation were enrolled. The median age was 59 years. A total of 115 (75.7%) patients were non-small cell lung cancer (NSCLC), 22 (14.5%) were small cell lung cancer (SCLC), and 15 (9.9%) were other pathological types. Among them, 58 received chemoradiation combined with ICIs and 94 received chemoradiation alone. The rate of grade ≥2 pneumonitis was significantly higher in the combination therapy group (39.7% vs. 22.3%, P=0.028) and was associated with the use of ICIs [odds ratio (OR): 2.641, 95% confidence interval (CI): 1.244-5.608, P=0.011] and percent volume of the lung receiving ≥30 Gy (V30) (OR: 1.728, 95% CI: 1.214-2.460, P=0.002). The history of chronic lung disease was the independent risk factor (OR: 6.359, 95% CI: 1.953-20.705, P=0.002) of grade ≥3 pneumonitis. In the combination group, univariate and multivariate analyses revealed that V5, V20, V30, and mean lung dose (MLD) were not associated with pneumonitis, whereas the history of chronic lung disease was an independent risk factor of grade ≥3 pneumonitis (OR: 8.351, 95% CI: 1.469-47.484, P=0.017). Conclusions: The incidence of pneumonitis of ICIs combined with chemoradiation was higher than chemoradiation alone, but manageable. The combination therapy should be applied with caution especially in patients with history of chronic lung disease.

Unlocking the link between temporomandibular disorders and suicide ideation in pre-orthodontic patients: A moderated mediation model of depression and anxiety.

BACKGROUND: Temporomandibular disorders (TMD) are a series of musculoskeletal diseases with high prevalence. A few studies have reported the correlation between TMD and suicide ideation (SI). However, the underlying mechanism of the relationship lacks in-depth exploration. METHODS: A cross-sectional study was conducted among 954 pre-orthodontic patients. TMD assessment was based on the quintessential five TMD symptoms (5Ts) questionnaire. Anxiety, depression and pain catastrophizing was evaluated by Seven-item Generalized Anxiety Disorder Scale (GAD-7), Nine-item Patient Health Questionnaire (PHQ-9), and Pain Catastrophizing Scale (PCS), respectively. Correlational and moderated mediated analysis was preformed to demonstrate the relationship between TMD and SI. RESULTS: In pre-orthodontic patients, 31.87 % reported having TMD symptoms and 6.50 % declared SI during the past two weeks. The SI prevalence was 10.53 % in participants with TMD and 4.62 % in those without TMD. Intra-articular TMD, rather than pain-related TMD were especially related with SI. Individuals with TMD had higher risk to SI (rs = 0.112, adjusted OR = 2.213, p < 0.001). The effect of TMD on SI was fully mediated through depression (ß = 0.445, 95 % CI = [0.326, 0.563]). Anxiety exerted a negative moderating effect on the depression-SI relation (ß = -0.033, 95 % CI = [-0.047, -0.019]). LIMITATIONS: This study was a single-centered and cross-sectional survey. The data collection relied on self-reporting methods. CONCLUSIONS: A positive link between TMD and SI was disclosed. The effect of TMD on SI was fully mediated through depression with anxiety as a negative moderator.

Identifying Key Genes and Functionally Enriched Pathways in Osteoporotic Patients by Weighted Gene Co-Expression Network Analysis.

Osteoporosis is a systemic bone disease characterized by low bone mineral density and bone microstructure damage, resulting in increased bone fragility and fracture risk. The present study aimed to identify key genes and functionally enriched pathways in osteoporotic patients. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to microarray datasets of blood samples of osteoporotic patients from the Sao Paulo Ageing & Health [SPAH] study (26 osteoporotic samples and 31 normal samples) to construct co-expression networks and identify hub gene. The results showed that HDGF, AP2M1, DNAJC6, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, IGKV3-7, IGKV3D-11, and IGKV1D-42 are genes which were associated with the disease status of osteoporosis. Differentially expressed genes are enriched in proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. Functional enrichment analysis demonstrated that genes in the tan module were enriched in immune-related functions, indicating that the immune system plays a critical role in osteoporosis. Validation assay demonstrated that the HDGF, AP2M1, TMEM183B, and MFSD2B levels were decreased in osteoporosis samples compared with healthy controls, while the levels of IGKV1-5, IGKV1-8, and IGKV1D-42 were increased in osteoporosis samples compared with healthy controls. In conclusion, our data identified and validated the association of HDGF, AP2M1, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, and IGKV1D-42 with osteoporosis in elderly women. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of osteoporosis.

Fibula allograft transplantation combined with locking plate for treatment of recurrent monostotic fibular fibrous dysplasia: A case report.

BACKGROUND: Fibrous dysplasia is a congenital disorder in which normal bone is replaced by fibro-osseous tissue or irregular trabeculae of woven bone intermixed with mature collagenous tissue. A single or multiple bones are affected. This rare bone disorder has three clinical patterns including monostotic, polyostotic, and that associated with McCune-Albright syndrome. Most studies report primary fibrous dysplasia. However, a few cases of recurrent monostotic fibular fibrous dysplasia have been reported. Here, we report a therapeutic strategy for recurrent fibular fibrous dysplasia. CASE SUMMARY: A 4-year-old boy was admitted for persistent pain in the left lower limb and abnormal gait over the previous 9 mo. He had no history of present or past illness. Preoperative imaging data showed erosion-like changes with bone expansion of the left middle and lower fibular segment. Tumor tissue in the fibular bone marrow cavity was removed by curettage, and rapid intraoperative pathological examination suggested fibular fibrous dysplasia. An allograft was implanted into the fibular medullary cavity. However, he was readmitted with clinical symptoms including persistent pain, abnormal gait, and local swelling at the age of 6 years. He was diagnosed with recurrent fibular fibrous dysplasia based on the second medical examination. He underwent fibular bone tumor radical resection and longus fibular allograft transplantation combined with fibular bone locking plate and screws. Good host bone to allogenic bone graft fusion was observed by the physician on postoperative regular follow-up. CONCLUSION: Radical resection of fibrous dysplasia and longus fibula allograft combined with internal fixation for reconstruction are suitable for the treatment of recurrent monostotic fibular fibrous dysplasia.

Orthodontic Patients with Poor Oral Health-Related Quality of Life are More Likely to Have Emotional Distress: A Cross-Sectional Study.

Objective: This study aims to investigate the relationship between oral health-related quality of life (OHRQoL) and emotional distress (ED), including anxiety and depression, in orthodontic patients. Methods: A cross-sectional study was conducted involving 603 orthodontic patients, consisting of 401 females (66.5%) with a mean age of 24.15 ± 7.72 and 202 males (33.5%) with a mean age of 24.16 ± 7.72. A questionnaire containing questions of demographic information, the Oral Health Impact Profile (OHIP-14) and the Huaxi emotional-distress index (HEI) was employed to assess OHRQoL and ED. According to the HEI score, the respondents were divided into ED group (HEI > 8) and non-ED group (HEI ≤ 8). Data were analyzed using Kolmogorov-Smirnov test, Mann-Whitney test and logistic regression analysis with the significance level set at p < 0.05. Results: The prevalence of poor OHRQoL and ED of the study sample was 28.4% and 19.57%, respectively. There was a significantly higher prevalence of ED among poor OHRQoL patients (35.67%) compared to those with good OHRQoL (13.19%) (p < 0.001). Poor OHRQoL and risky drinking behavior addressed higher significant correlation with ED patients than non-ED patients (p < 0.05). There were no statistical differences in other factors such as gender, age, and appliance type (p > 0.05). Poor OHRQoL orthodontic patients were at a higher risk of suffering from anxiety and depression compared to those with good OHRQoL (age-risky drinking behavior-sex-adjusted: OR = 4.00; all p < 0.001). Conclusion: Oral health-related quality of life (OHRQoL) is related to emotional stress. Namely, patients with poor OHRQoL are more likely to experience anxiety and depression. As a result, orthodontists should consistently assess the emotional well-being and OHROoL of patients over the treatment course for better treatment outcomes.