Advances in experimental models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent articular inflammation and joint damage. RA was first described over 200 years ago; however, its etiology and pathophysiology remain insufficiently understood. The current treatment of RA is mainly empirical or based on the current understanding of etiology with limited efficacy and/or substantial side effects. Thus, the development of safer and more potent therapeutics, validated and optimized in experimental models, is urgently required. To improve the transition from bench to bedside, researchers must carefully select the appropriate experimental models as well as draw the right conclusions. Here, we summarize the establishment, pathological features, potential mechanisms, advantages, and limitations of the currently available RA models. The aim of the review is to help researchers better understand available RA models; discuss future trends in RA model development, which can help highlight new translational and human-based avenues in RA research.

Effect of stress urinary incontinence on vaginal microbial communities.

BACKGROUND: Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited. RESULTS: This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering. CONCLUSION: The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.

Risk of Clostridioides difficile infection in inflammatory bowel disease patients undergoing vedolizumab treatment: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. METHOD: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta". RESULTS: Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010-0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002-0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73-2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04-0.63) for UC and 1.29 (95% CI 0.41-4.04) for CD. CONCLUSION: The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. TRIAL REGISTRATION: The study was registered on the PROSPERO registry (CRD42023465986).

Multimorbidity in patients with monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma, is present in over 5% of adults aged 70 and older, a population with a high prevalence of multimorbidity. MGUS is often diagnosed incidentally when patients seek care for unrelated conditions. Our study sought to examine patterns of multimorbidity among MGUS patients, as overall health may impact patient care and the prioritization of MGUS surveillance. We examined patterns of comorbidities in 429 patients diagnosed with MGUS (2007-2015) and 1287 matched controls. Twenty-seven conditions were defined at diagnosis/index date using algorithms developed by the Centers for Medicare and Medicaid Chronic Conditions Warehouse. Patterns of common comorbidities were identified individually, in dyads and triads, and compared between MGUS cases and controls. We conducted a latent class analysis to identify comorbidity patterns among cases only. We also examined comorbidity patterns among a subset of 32 MGUS cases who progressed to cancer during the study period. The most common comorbidities among both MGUS cases and controls included hypertension and hyperlipidemia. Anemia (cases: 43%; controls: 16%) and chronic kidney disease (CKD; cases: 36%; controls: 18%), and dyads and triads containing those conditions, were more common among cases. Latent class analysis identified three classes of comorbidity among MGUS cases: hypertension-hyperlipidemia plus anemia and CKD (31%); low comorbidity burden (17%); and hypertension-hyperlipidemia alone (52%). The higher prevalence among cases of anemia and CKD, which may be involved in the pathogenesis of, or surveillance for, MGUS, warrants additional investigation.

Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

Tet2-mediated DNA demethylation regulates the proliferation and apoptosis of human leukemia K562 cells.

TET2 is a member of the TET protein family which is responsible for active DNA demethylation through catalyzing the successive oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), and mutations of Tet2 frequently lead to hematological malignancies. However, the relationship between Tet2-mediated demethylation and hematological malignancies is unclear. The human leukemia K562 cell line is an immortalized leukemia line that serves as an in vitro model of erythroleukemia. In this study, we investigated the effect of Tet2-mediated demethylation on the apoptosis and proliferation of human leukemia K562 cells and found that knockdown of Tet2 promoted and inhibited K562 cell proliferation and apoptosis, respectively, while upregulation of TET2 enzymatic activity via alpha-ketoglutaric acid (α-KG) had the opposite effects. Therefore, the Tet2 gene acts as a potential target for the treatment of leukemia, and small molecules that target the Tet2 gene may be used to screen antitumor drugs for hematological malignancies.

Effect of radiofrequency combined with magnetic stimulation on mild and moderate pelvic organ prolapse. / å°„é¢‘è”åˆç£åˆºæ¿€æ²»ç–—å¯¹è½»ä¸­åº¦ç›†è ”å™¨å®˜è„±åž‚çš„ç–—æ•ˆ.

OBJECTIVES: The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited. This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse. METHODS: Patients who completed the treatment in the Third Xiangya Hospital, Central South University were screened, and were divided into 2 groups based on different treatment plans. There were 28 patients who completed magnetic stimulation therapy (the magnetic stimulation therapy group) and 21 patients who completed radiofrequency combined with magnetic stimulation therapy (the combined treatment group). The pelvic organ prolapse quantitation (POP-Q), pelvic floor muscle strength, and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups, and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode. RESULTS: The POP-Q evaluation results of Aa, Ap, and C points after the treatment in both groups were better than those before the treatment, with statistical significance (all P<0.05). The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group, with statistical significance (P<0.05). Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group, with statistical significance (P<0.05). The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group, with significant statistical significance (P<0.01). CONCLUSIONS: The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.

Multi-trajectory models of serum biomarkers among patients with monoclonal gammopathy of undetermined significance.

Understanding the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is needed to identify patients who would benefit from closer clinical surveillance. Given that two of the defining criteria of MM are renal failure and anemia, we described the trajectories of creatinine (Cr) and hemoglobin (Hgb) over time in patients with a diagnosis of MGUS. Patients diagnosed with MGUS (n = 424) were identified by a previously validated case-finding algorithm using health claims and electronic health record data (2007-2015) and followed through 2018. Group-based trajectory modeling identified patients with distinct laboratory value trajectories of Cr (mg/dl) and Hgb (g/dl). Most patients were non-Hispanic White (97.6%) with a mean age of 75 years at MGUS diagnosis. Three multi-trajectory groups were identified: (1) Normal Cr/Hgb (n = 225; 53.1%)-stable serum Cr levels and decreasing, normal Hgb levels; (2) Normal Cr/lower-normal Hgb group (n = 188; 44.3%)-stable, slightly elevated levels of Cr and decreasing levels of Hgb; and (3) High Cr/borderline Hgb group (n = 11; 2.6%)-increased Cr levels and stable low levels of Hgb. Patients with MGUS in Group 2 were older than patients in other groups, and patients in group 3 had more comorbidities than participants in all other groups. Few patients developed MM during the study period. We were able to identify distinct biomarker trajectories in patients with MGUS over time. Future research should investigate how these trajectories may be related to the risk of progression to MM, including M-protein levels.

Differences in Hospital, Emergency Room and Outpatient Visits Among Adults With and Without Monoclonal Gammopathy of Undetermined Significance.

INTRODUCTION: This study evaluated the impact of receiving a monoclonal gammopathy of undetermined significance (MGUS) diagnosis on healthcare utilization from patients at a community-based multispecialty provider organization. METHODS: A cohort of patients with MGUS (n = 429) were matched on sex, age, and length of enrollment to a cohort of patients without MGUS (n = 1286). Healthcare utilization was assessed: 1-12 months before, 1 month before and after, and 1-12 months after diagnosis/index date. Multivariable conditional Poisson models compared change in utilization of each service in patients with and without MGUS. RESULTS: During the 2 months around diagnosis/index date, the rates of emergency room, hospital and outpatient visits were higher for patients with MGUS than patients without MGUS. In the year before MGUS diagnosis, the association was still elevated, although attenuated. CONCLUSION: Understanding the care of MGUS patients is important given that multiple myeloma patients with a pre-existing MGUS diagnosis may have a better prognosis.

MicroRNA-425-5p Is Involved in the Development of Diabetic Retinopathy and Regulates the Proliferation and Migration of Retinal Microvascular Endothelial Cells.

INTRODUCTION: The objective of this article was to detect the expression pattern and clinical value of miR-425-5p in diabetic retinopathy (DR) patients and investigate its effect on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) in a high glucose (HG) state. METHODS: The serum miR-425-5p level of the subjects was determined using quantitative real-time PCR. The diagnostic value of serum miR-425-5p was validated using the receiver operating characteristic curve. Pearson analysis detected the correlation between clinical indicators and microRNA. The influence of miR-425-5p on cell proliferation and migration under HG conditions was calculated by using Cell Counting Kit-8 and Transwell assay. RESULTS: Serum miR-425-5p levels showed a gradual increasing trend in the healthy control group, the diabetic mellitus patients without DR, and DR patients. Moreover, the levels of miR-425-5p in proliferative DR (PDR) patients were elevated than that of non-PDR (NPDR) patients. Furthermore, upregulated miR-425-5p had a high diagnostic value for DR patients and can distinguish PDR patients from NPDR patients. The expression of miR-425-5p was significantly positively correlated with the fasting plasma glucose, glycosylated hemoglobin (HbA1C), homeostasis model assessment of insulin resistance, and disease course of the patients. Under HG conditions, overexpression of miR-425-5p promoted HRMEC proliferation and migration, while inhibition of miR-425-5p led to opposite results. CONCLUSION: Present research confirmed that serum miR-425-5p levels in DR are marked by elevation. High expression of miR-425-5p can be used as a feasible diagnostic biomarker for DR patients and can predict the development and severity of DR. Moreover, inhibiting the expression of miR-425-5p levels under the condition of hyperglycemia may be used as a valuable therapeutic strategy for preventing the pathogenesis of DR.

Observation on the effect of platelet-rich plasma combined with drugs in the treatment of herpes zoster neuralgia.

PURPOSE: To observe the effect of ultrasound-guided platelet-rich plasma (PRP) injection in the treatment of herpes zoster neuralgia (HZN). METHODS: Eighty patients with HZN were randomly divided into observation group and control group, with 40 cases in each group. The observation group was treated with ultrasound-guided PRP injection of target nerves combined with drugs. The control group was treated with drugs alone. The pain scores of before treatment (T0), and 1 week (T1), 1 month (T2), 3 months (T3) and 6 months (T4) after treatment were recorded with Numerical Rating Scale (NRS). The sleep quality of patients was assessed with the Athens Insomnia Scale, and the dosage used at each time point, skin lesions, adverse reactions, and the occurrence of postherpetic neuralgia (PHN) were recorded. RESULTS: The NRS score of the two groups after treatment showed a downward trend. Compared with T0 at each time point, the difference was statistically significant (p < 0.05). And the NRS score of the observation group was lower than control group (p < 0.05). The sleep quality of the observation group was better. The dosage of the observation group was less, and the time of herpes dry-up, scab crusting and shedding in the observation group was significantly shorter (p < 0.05). The incidence of dizziness, lethargy, ataxia and PHN in the observation group was significantly reduced (p < 0.05). CONCLUSION: Compared with traditional drug treatment alone, the ultrasound-guided PRP injection has the advantages of better analgesia and fewer side effects, which provides a new idea for the treatment of HZN.

Developmental potential of different embryos on day 3: a retrospective study.

To investigate how different quality of day 3 (D3) embryos affect blastocyst formation and clinical outcomes. This retrospective study analysed 699 patients undergoing assisted reproductive technology (ART) between January 2017 and February 2021. A total of 2517 D3 embryos were transferred to blastocyst medium for extended culture. D3 embryos were divided into five groups. Grade A, 6-10 cells, symmetrical blastomeres and <20% fragmentation; grade B, 6-10 cells, uneven blastomeres and ≥20% fragmentation; grade C, >10 cells, symmetrical blastomeres and <20% fragmentation; grade D, >10 cells, uneven blastomeres and ≥20% fragmentation; grade E, <6 cells. Status of day 5 (D5) and day 6 (D6) blastocysts and the clinical outcomes (blastocyst transfer) of each D3 embryo were recorded. The grade C group showed a higher D5 blastocyst formation rate and a high-quality blastocyst rate than other groups (p<.05). However, the clinical pregnancy rates in the grade A group were higher than other groups (p<.05). Embryos with low speed of development (grade E group) showed considerable clinical outcomes that were still worth investigating. D3 embryos with less fragmentation and ≥6 symmetrical blastomeres revealed a higher developmental potential, while embryos with 6-10 blastomeres showed the ideal clinical outcomes.Impact StatementWhat is already known on this subject? Accurate embryo evaluation can effectively reflect the developmental potential of different embryos. The number of blastomeres, proportion of fragmentation, and blastomere symmetry are three important and popular morphologic parameters used for evaluating day 3 (D3) embryos. However, in existing reports, combining these three parameters for embryo evaluation often results in different results. This is because different researchers have chosen different criteria for these three parameters.What do the results of this study add? In this retrospective study, we summarised the medical records of our reproductive centre in the past three years, redefined the evaluation method of the D3 embryos, and analysed the corresponding developmental potential and clinical outcomes. We conclude that although the embryonic development potential of grade C embryos (>10 cells, symmetrical blastomeres and/or <20% fragmentation) is relatively good, the results of grade A embryos (6-10 cells, symmetrical blastomeres and/or <20% fragmentation) are better in terms of clinical outcomes.What are the implications of these findings for clinical practice and/or further research? We believe this is meaningful for embryologists to choose embryos for transfer and predict the clinical outcome of IVF cycles.

Therapeutic effect of proprioception training combined with pelvic floor electrical stimulation biofeedback on postpartum pelvic floor dysfunction. / æœ¬ä½“æ„Ÿè§‰è®­ç»ƒè”åˆç›†åº•ç”µåˆºæ¿€ç”Ÿç‰©åé¦ˆå¯¹äº§åŽç›†åº•åŠŸèƒ½éšœç¢æ€§ç–¾ç— çš„æ²»ç–—æ•ˆæžœ.

OBJECTIVES: Pelvic floor tendons, fascia, and ligaments are rich in proprioceptors. Proprioceptive training can stimulate local proprioceptors to increase neuromuscular responses and promote the recovery of muscle and fascial ligament functions. This study aims to observe the therapeutic effect of proprioception training combined with pelvic floor electrical stimulation biofeedback on postpartum pelvic floor dysfunction (PFD), and to provide evidence for the treatment of postpartum PFD. METHODS: A total of 108 puerpera with postpartum PFD were selected and divided into a control group ( n =50) and an experimental group ( n =58). Puerpera in the control group received pelvic floor electrical stimulation biofeedback treatment. Puerpera in the experimental group received proprioception training combined with pelvic floor electrical stimulation biofeedback treatment. After one course of treatment, the pelvic floor muscle strength, muscle endurance, repetitive contraction ability, rapid contraction ability, percentage of normal vaginal posterior wall elevation, percentage of normal lower abdominal muscle synergistic contraction, percentage of normal reflex contraction during coughing, incidence of stress urinary incontinence (SUI), and staging of pelvic organ prolapse (POP) were compared before and after treatment between the 2 groups. RESULTS: After treatment, all indexes of the 2 groups were better than those before treatment; the pelvic floor muscle strength, muscular endurance, repetitive contraction ability, and rapid contraction ability of the experimental group were better than those of the control group (all P <0.05); the percentage of normal lower abdominal muscle synergistic contraction and percentage of normal reflex contraction during coughing of the experimental group were higher than those of the control group (both P <0.05); the incidence of SUI in the experimental group was lower than that in the control group ( P <0.05); the percentage of POP staging II in the experimental group was significantly lower than that in the control group ( P <0.05). There was no significant difference in the percentage of normal posterior vaginal wall elevation after treatment between the 2 groups ( P >0.05). CONCLUSIONS: Proprioception training combined with pelvic floor electrical stimulation biofeedback could improve the rehabilitation effect of postpartum pelvic floor dysfunction and promote the recovery of pelvic floor function, which possesses important clinical application value.

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Characteristics of endoscopic and pathological findings of amebic colitis.

BACKGROUND: The clinical features of amoebic colitis resemble those of inflammatory bowel disease (IBD), and therefore the risk of misdiagnosis is very high. The aim of this study was to analyse the characteristics of the endoscopic and pathological findings of amebic colitis and the lessons from our patients, which were useful for diagnosing the amebic colitis timely and avoiding the serious complication. METHODS: We retrospectively reviewed data of all amebic colitis admitted to Beijing Friendship Hospital from January 2015 to January 2020. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and histological examination, no ELISA stool antigen or PCR tests were used. RESULTS: 16 patients were diagnosed with amebic colitis by the colonoscopy accompanied by biopsy and microscopic examination. At first time, 12 (75%) patients were misdiagnosed as IBD. Cecum was the most common site of amebic colitis (100%), and the caecum and rectum were also involved in many lesions (68.75%). Multiple lesions of erosion and/or ulcer were recognized in all patients (100%).The endoscopic findings included multiple irregular shaped ulcers and erosions with surrounding erythema, and the ulcers and erosions were covered by the white or yellow exudates. The intervening mucosae between the ulcers or erosions were normal. The features of rectums can be divided to 2 types: in 6 patients (54.5%), the irregular ulcer or erosions covered with white or yellow exudates were observed in rectum and cecum, and the bloody exudates in rectum were more severe than those in cecum; in other 5 patients (45.5%), rectal lesions were much less severe than those in cecum, the small superficial erosion or reddened mucosa were observed in the rectal ampulla. All patients were diagnosed as detection of amebic trophozoites from HE-stained biopsy specimens. The number of trophozoites ranged from 1/HPF to > 50/HPF. Among 16 cases, mild architectural alteration of colon crypt were observed in 10 cases (62.5%), and serious architectural alteration of colon crypt was found which had crypt branch in 1 case (16.7%). Cryptitis was observed in 12 cases (75%) and its severity was mild or moderate. No crypts abscess was observed in all cases. CONCLUSIONS: The colonoscopy with histological examination are very important to diagnose the amebic colitis. Detect the amoebic trophozoites in the exudates by histological examination is the vital. Sometimes a negative biopsy does not rule out amebiasis, repeated biopsies may be needed to make the diagnosis.

Discovery of tetrandrine derivatives as tumor migration, invasion and angiogenesis inhibitors.

Metastatic progression of cancer is a complex and clinically daunting process, with migration, invasion and angiogenesis being the key features. Tetrandrine (TET) is a typical dibenzylisoquinoline alkaloid with promising anti-tumor activity. In our previous work, a number of TET derivatives were designed and synthesized with obvious anti-proliferation activities against cancer cells, however, the anti-metastatic effects of these compounds were not evaluated. In the current investigation, five TET derivatives (8, 18, 32, 71, and 72) with pronounced anti-proliferative activities (IC50 values of 1.00, 1.91, 3.43, 3.78, and 1.93 µM, respectively) against human umbilical vein endothelial cells (HUVECs) were screened out. Scratch assays showed that these compounds significantly suppressed the migration of HUVECs and induced their apoptosis. Among them, derivatives 8 and 72 obviously inhibited the proliferation, colony formation and invasion of HCT-15 cells. Tube formation assays revealed that 4 µM of 8 or 72 remarkably inhibited the tube forming capacity of HUVECs. Moreover, 8 and 72 surpressed the formation of filopodia in HUVECs and severely impaired their motility. Both compounds effectively inhibited the angiogenesis in the zebrafish model with low toxicities in vivo. These results indicated that TET derivatives 8 and 72 are promising anti-metastatic inhibitors.

Identifying monoclonal gammopathy of undetermined significance in electronic health data.

PURPOSE: Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent yet largely asymptomatic precursor to multiple myeloma. Patients with MGUS must undergo regular surveillance and testing, with few known predictors of progression. We developed an algorithm to identify MGUS patients in electronic health data to facilitate large-scale, population-based studies of this premalignant condition. METHODS: We developed a four-step algorithm using electronic health record and health claims data from men and women aged 50 years or older receiving care from a large, multispecialty medical group between 2007 and 2015. The case definition required patients to have at least two MGUS ICD-9 diagnosis codes within 12 months, at least one serum and/or urine protein electrophoresis and one immunofixation test, and at least one in-office hematology/oncology visit. Medical charts for selected cases were abstracted then adjudicated independently by two physicians. We assessed algorithm validity by positive predictive value (PPV). RESULTS: We identified 833 people with at least two MGUS diagnosis codes; 429 (52%) met all four algorithm criteria. We randomly selected 252 charts for review, including 206 from patients meeting all four algorithm criteria. The PPV for the 206 algorithm-identified charts was 76% (95% CI, 70%-82%). Among the 49 cases deemed to be false positives (24%), 33 were judged to have multiple myeloma or another lymphoproliferative condition, such as lymphoma. CONCLUSIONS: We developed a simple algorithm that identified MGUS cases in electronic health data with reasonable accuracy. Inclusion of additional steps to eliminate cases with malignant disease may improve algorithm performance.

Occupational benzene exposure and the risk of genetic damage: a systematic review and meta-analysis.

BACKGROUND: Benzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links between benzene and various types of genetic damage indicators have been evaluated in several studies, but their results remain inconsistent. So we conducted a meta-analysis, and to explore the influence of low concentration benzene exposure on workers' genetic damage indicators using 3.25 mg/m3 as the boundary value, in order to provide a basis for improved prevention and control of the harm from benzene exposure to the occupational population. METHODS: We conducted a search of five databases, including Pub Med, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data and Chongqing VIP, to identify relevant articles up to December 25, 2018. Two researchers independently extracted and evaluated the data according to the inclusion and exclusion criteria of the literature. The imported articles were managed by Endnote X7, and the data were extracted and sorted by Excel 2013. We utilized Stata 12.0 software to perform the meta-analysis in the present study. RESULTS: A total of 68 eligible articles were finally included for the synthetic analyses. The meta-analysis results showed that occupational benzene exposure led to significantly increased Micronucleus (MN) frequency, Sister chromatid exchange (SCE) frequency, Chromosome aberration (CA) frequency, Olive Tail moment (OTM), Tail moment (TM), Tail length (TL), and Tail DNA% (T DNA%) compared to the control group (P < 0.05), and the pooled effect value estimates were 1.36, 0.98, 0.76, 1.06, 0.96, 1.78, and 1.42, respectively. Subsequent analysis of the effect of low concentration benzene exposure on genetic damage found significantly increased MN frequency increased compared with the control group (P < 0.05). CONCLUSIONS: Occupational benzene exposure can affect multiple genetic damage indicators. Even at an exposure concentration lower than 3.25 mg/m3, benzene exposure has genotoxicity. These data provide an important scientific basis for the further revision of occupational disease prevention strategies. At the same time, increased attention should be focused on the health monitoring of the occupational population exposed to benzene, and health management should be strengthened to improve the health of the occupational population.