Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Dengue encephalopathy in an adult due to dengue virus type 1 infection.

BACKGROUND: Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients. CASE PRESENTATION: A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient's serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae. CONCLUSION: Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.

Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Liquid-Metal Molecular Scissors.

Molecules are the smallest units of matter that can exist independently, relatively stable, maintaining their physical and chemical activities. The key factors that dominate the structures and properties of molecules include atomic species, alignment commands, and chemical bonds. Herein, we reported a generalized effect in which liquid metals can directly cut off oxygen-containing groups in molecular matter at room temperature, allowing the remaining groups to recombine to form functional materials. Thus, we propose basic liquid-metal scissors for molecular directional clipping and functional transformations. As a proof of concept, we demonstrate the capabilities of liquid-metal scissors and reveal that the gallium on the surface of liquid metals directly extracts oxygen atoms from H2O or CH3OH molecules to form oxides. After clipping, the remaining hydrogen atoms from the H2O molecules recombine to form H2, while the remaining fragments of CH3OH produce H2, carbon materials, and carboxylates. This finding refreshes our basic understanding of chemistry and should lead to the development of straightforward molecular weaving techniques, which can help to overcome the limitations of molecular substances with single purposes. It also opens a universal route for realizing future innovations in molecular chemical engineering, life sciences, energy and environment research, and biomedicine.

Development of a TLR-Based Model That Can Predict Prognosis, Tumor Microenvironment, and Drug Response for Esophageal Squamous Cell Carcinoma.

The toll-like receptor (TLR) family is an important class of proteins involved in the immune response. However, little is known about the association between TLRs and Esophageal squamous cell cancer (ESCC). We explored differentially expressed genes (DEGs) between ESCC and esophagus tissues in TCGA and GTEx database. By taking the intersection with TLR gene set and using univariate Cox analysis and multivariate Cox regression analysis to discriminate the hub genes, we created a TLR-prognostic model. Our model separated patients with ESCC into high- and low-risk score (RS) groups. Prognostic analysis was performed with Kaplan-Meier curves. The two groups were also compared regarding tumor immune microenvironment and drug sensitivity. Six hub genes (including CD36, LGR4, MAP2K3, NINJ1, PIK3R1, and TRAF3) were screened to construct a TLR-prognostic model. High-RS group had a worse survival (p < 0.01), lower immune checkpoint expression (p < 0.05), immune cell abundance (p < 0.05) and decreased sensitivity to Epirubicin (p < 0.001), 5-fluorouracil (p < 0.0001), Sorafenib (p < 0.01) and Oxaliplatin (p < 0.05). We constructed a TLR-based model, which could be used to assess the prognosis of patients with ESCC, provide new insights into drug treatment for ESCC patients and investigate the TME and drug response.

Do we know enough about the effect of low-dose computed tomography screening for lung cancer on mortality to act? An updated systematic review, meta-analysis and network meta-analysis of randomised controlled trials 2017 to 2021.

BACKGROUND: For people at high risk of lung cancer, low-dose computed tomography (LDCT) is proposed as a method to reduce mortality. METHODS: Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. RCTs of CXR screening were additionally included in the network meta-analyses. Bibliographic sources including MEDLINE, Embase, Web of Science and the Cochrane Library were searched to January 2017, and then further extended to November 2021. All key review steps were done by two persons. Quality assessment used the Cochrane Risk of Bias tool. Meta-analyses were performed. RESULTS: Nine RCTs, with up to 12.3 years of follow-up from randomisation, were included in the direct meta-analysis, which showed that LDCT screening was associated with a statistically significant decrease in lung cancer mortality (pooled relative risk (RR) 0.86, 95% confidence interval [CI] 0.77 to 0.96). There was a statistically non-significant decrease in all-cause mortality (pooled RR 0.98, 95% CI 0.95 to 1.01). The statistical heterogeneity for both outcomes was minimal. Network meta-analysis including the nine RCTs in the direct meta-analysis plus two further RCTs comparing CXR with usual care confirmed the size of the effect of LDCT on lung cancer mortality and that this was very similar irrespective of whether the comparator was usual care or CXR screening. CONCLUSIONS: LDCT screening is effective in reducing lung cancer mortality in high-risk populations. The uncertainty of its effect on lung cancer mortality observed in 2018 has been much reduced with new trial results and updates to existing trials, emphasising the importance of updating systematic reviews. Although there are still a number of RCTs unreported or in progress, we predict that further evolution of summary mortality estimates is unlikely. The focus for debate now moves to resolving uncertainty about the cost-effectiveness of LDCT screening taking into account the balance between benefits and harms which occur in all screening programmes.

Safety and efficacy of telitacicept in refractory systemic lupus erythematosus patients who failed treatment with belimumab : A case series.

OBJECTIVE: This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. A review of published reports on telitacicept for SLE was also performed. METHODS: A retrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms "systemic lupus erythematosus" and "telitacicept" were used to identify patients reported in the English medical literature. RESULTS: Identified were 14 refractory SLE patients, 3 males (21%) and 11 females (79%). The median age was 32.9 years. The median disease duration was 8.9 years. Patients in this cohort received telitacicept for an average of 34.1 weeks (17-62 weeks) and the total SLE responder index 4 (SRI-4) response rate was 78.9% (n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87-9.28) to 4.29 at the endpoint (95% CI 3.4-5.16). All cases (100%) had hypocomplementemia at baseline, and 7 cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24­h urinary protein value of the 13 cases with proteinuria (baseline 24­h urinary protein > 0.5 g/d) displayed a reduction, and 3 values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. CONCLUSION: This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be a promising drug for the treatment of refractory lupus hepatitis.

Real-World Study on Chai-Shi-Jie-Du Granules for the Treatment of Dengue Fever and the Possible Mechanisms Based on Network Pharmacology.

Objectives: Traditional Chinese medicine (TCM) is a widely used method for treating dengue fever in China. TCM improves the symptoms of patients with dengue, but there is no standard TCM prescription for dengue fever. This real-world study aimed to evaluate the effects of Chai-Shi-Jie-Du (CSJD) granules for the treatment of dengue fever and the underlying mechanisms. Methods: We implemented a multicenter real-world study, an in vitro assay and network pharmacology analysis. Patients from 5 hospitals in mainland China who received supportive western treatment in the absence or presence of CSJD were assigned to the control and CSJD groups between 1 August and 31 December 2019. Propensity score matching (PSM) was performed to correct for biases between groups. The clinical data were compared and analyzed. The antidengue virus activity of CSJD was tested in Syrian baby hamster kidney (BHK) cells using the DENV2-NGC strain. Network pharmacological approaches along with active compound screening, target prediction, and GO and KEGG enrichment analyses were used to explore the underlying molecular mechanisms. Results: 137 pairs of patients were successfully matched according to age, sex, and the time from onset to presentation. The time to defervescence (1.7 days vs. 2.5 days, P < 0.05) and the disease course (4.1 days vs. 6.1 days, P < 0.05) were significantly shorter in the CSJD group than those in the control group. CSJD showed no anti-DENV2-NGC virus activity in BHK cells. Network pharmacology analysis revealed 108 potential therapeutic targets, and the top GO and KEGG terms were related to immunity, oxidative stress response, and the response to lipopolysaccharide. Conclusions: CSJD granules exhibit high potential for the treatment of dengue fever, and the therapeutic mechanisms involved could be related to regulating immunity, moderating the oxidative stress response, and the response to lipopolysaccharide.

Comparison of curative effect between OBS assisted by 3D printing and PFNA in the treatment of AO/OTA type 31-A3 femoral intertrochanteric fractures in elderly patients.

Objective: To compare and analyze the Ortho-Bridge System (OBS) clinical efficacy assisted by 3D printing and proximal femoral nail anti-rotation (PFNA) of AO/OTA type 31-A3 femoral intertrochanteric fractures in elderly patients. Methods: A retrospective analysis of 25 elderly patients diagnosed with AO/OTA type 31-A3 femoral intertrochanteric fracture was conducted from January 2020 to August 2022 at Yan'an Hospital, affiliated to Kunming Medical University. The patients were divided into 10 patients in the OBS group and 15 in the PFNA group according to different surgical methods. The OBS group reconstructed the bone models and designed the guide plate by computer before the operation, imported the data of the guide plate and bone models into a stereolithography apparatus (SLA) 3D printer, and printed them using photosensitive resin, thus obtaining the physical object, then simulating the operation and finally applying the guide plate to assist OBS to complete the operation; the PFNA group was treated by proximal femoral nail anti-rotation. The operation time, the intraoperative blood loss, Harris hip score (HHS), Oxford Hip Score (OHS), and complications were compared between the two groups. Results: The operation time and the intraoperative blood loss in the PFNA group were less than that in the OBS group, and there was a significant difference between the two groups (P < 0.05). The HHS during the 6th month using OBS was statistically higher than PFNA (P < 0.05), however, there were no significant differences in OHS during the 6th month between the OBS group and PFNA group (P > 0.05). The HHS and OHS during the 12th month in the OBS group were statistically better than in the PFNA group (P < 0.05). Conclusion: The OBS assisted by 3D printing and PFNA are effective measures for treating intertrochanteric fractures. Prior to making any decisions regarding internal fixation, it is crucial to evaluate the distinct circumstances of each patient thoroughly.

The effects of computerised decision support systems on nursing and allied health professional performance and patient outcomes: a systematic review and user contextualisation.

Background: Computerised decision support systems (CDSS) are widely used by nurses and allied health professionals but their effect on clinical performance and patient outcomes is uncertain. Objectives: Evaluate the effects of clinical decision support systems use on nurses', midwives' and allied health professionals' performance and patient outcomes and sense-check the results with developers and users. Eligibility criteria: Comparative studies (randomised controlled trials (RCTs), non-randomised trials, controlled before-and-after (CBA) studies, interrupted time series (ITS) and repeated measures studies comparing) of CDSS versus usual care from nurses, midwives or other allied health professionals. Information sources: Nineteen bibliographic databases searched October 2019 and February 2021. Risk of bias: Assessed using structured risk of bias guidelines; almost all included studies were at high risk of bias. Synthesis of results: Heterogeneity between interventions and outcomes necessitated narrative synthesis and grouping by: similarity in focus or CDSS-type, targeted health professionals, patient group, outcomes reported and study design. Included studies: Of 36,106 initial records, 262 studies were assessed for eligibility, with 35 included: 28 RCTs (80%), 3 CBA studies (8.6%), 3 ITS (8.6%) and 1 non-randomised trial, a total of 1318 health professionals and 67,595 patient participants. Few studies were multi-site and most focused on decision-making by nurses (71%) or paramedics (5.7%). Standalone, computer-based CDSS featured in 88.7% of the studies; only 8.6% of the studies involved 'smart' mobile or handheld technology. Care processes - including adherence to guidance - were positively influenced in 47% of the measures adopted. For example, nurses' adherence to hand disinfection guidance, insulin dosing, on-time blood sampling, and documenting care were improved if they used CDSS. Patient care outcomes were statistically - if not always clinically - significantly improved in 40.7% of indicators. For example, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity, and accurate triaging were features of professionals using CDSS compared to those who were not. Evidence limitations: Allied health professionals (AHPs) were underrepresented compared to nurses; systems, studies and outcomes were heterogeneous, preventing statistical aggregation; very wide confidence intervals around effects meant clinical significance was questionable; decision and implementation theory that would have helped interpret effects - including null effects - was largely absent; economic data were scant and diverse, preventing estimation of overall cost-effectiveness. Interpretation: CDSS can positively influence selected aspects of nurses', midwives' and AHPs' performance and care outcomes. Comparative research is generally of low quality and outcomes wide ranging and heterogeneous. After more than a decade of synthesised research into CDSS in healthcare professions other than medicine, the effect on processes and outcomes remains uncertain. Higher-quality, theoretically informed, evaluative research that addresses the economics of CDSS development and implementation is still required. Future work: Developing nursing CDSS and primary research evaluation. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in Health and Social Care Delivery Research; 2023. See the NIHR Journals Library website for further project information. Registration: PROSPERO [number: CRD42019147773].

Computerised decision support systems (CDSS) are software or computer-based technologies providing advice to professionals making clinical decisions ­ for example, which patients to treat first in emergency departments. CDSS improve some doctors' decisions and patients' outcomes, but we don't know if they improve nurses', midwives' and therapists' or other staff decisions and patient outcomes. Research into, and health professionals' use of, technology ­ for example, in video consultations ­ has grown since the last relevant systematic review in 2009. We systematically searched electronic databases for research measuring how well nurses, midwifes and other therapists/staff followed CDSS advice, how CDSS influence their decisions, how safe CDSS are, and their financial costs and benefits. We interviewed CDSS users and developers and some patient representatives from a general practice to help understand our findings. Of 35 relevant studies ­ from 36,106 initially found ­ most (71%) focused on nurses. Just over half (57%) involved hospital-based staff, and three-quarters (75%) were from richer countries like the USA or the UK. Research quality had not noticeably improved since 2009 and all studies were at risk of potentially misleading readers. CDSS improved care in just under half (47%) of professional behaviours, such as following hand-disinfection guidance, working out insulin doses, and sampling blood on time. Patient care ­ judged using outcomes like falls, pressure ulcers, diabetes control and triage accuracy ­ was better in 41% of the care measured. There wasn't enough evidence to judge CDSS safety or the financial costs and benefits of systems. CDSS can improve some nursing and therapist decisions and some patient outcomes. Studies mostly measure different behaviours and outcomes, making comparing them hard. Theories explaining or predicting how decision support systems might work are not used enough when designing, implementing or evaluating CDSS. More research into the financial costs and benefits of CDSS and higher-quality evidence of their effects are still needed. Whether decision support for nurses, midwives and other therapists reliably improves decision-making remains uncertain.

Prevalence, Characteristics, and Outcomes Associated with Acute Kidney Injury among Adult Patients with Severe Dengue in Mainland China.

Acute kidney injury (AKI) can occur in adult patients with severe dengue (SD) and have serious clinical outcomes. This study aimed to determine the prevalence, characteristics, risk factors, and clinical outcomes of AKI in adult patients with SD; the correlation of dengue virus (DENV) serological and virological profiles with AKI; and the clinical features of patients with severe AKI who received renal replacement treatment (RRT). This multicenter study was conducted in Guangdong Province, China, between January 2013 and November 2019. A total of 242 patients were evaluated, of which 85 (35.1%) developed AKI and 32 (13.2%) developed severe AKI (stage 3). Patients with AKI had a higher fatality rate (22.4% versus 5.7%; P < 0.001) and longer length of hospital stay (median: 13 versus 9 days; P < 0.001). Independent risk factors for AKI were hypertension (odds ratio [OR]: 2.03; 95% CI: 1.10-3.76), use of nephrotoxic drugs (OR: 1.90; 95% CI: 1.00-3.60), respiratory distress (OR: 4.15; 95% CI: 1.787-9.632), high international normalized ratio (INR) levels (OR: 6.44; 95% CI: 1.89-21.95), and hematuria (OR: 2.12; 95% CI: 1.14-3.95). There was no significant association between DENV serological and virological profiles and the presence or absence of AKI. Among patients with severe AKI, those who received RRT had a longer length of hospital stay and similar fatality rate. Hence, adult patients with SD should be closely monitored for the development of AKI to enable timely and appropriate therapy.

Clinical efficacy of belimumab in central nervous system demyelinating syndromes with systemic lupus erythematosus: A case series.

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple systems. Central nervous system (CNS) demyelinating syndromes are one of the rare neurological manifestations of SLE, whose diagnosis, treatment, and prognosis are rarely reported. Belimumab, an anti-BAFF monoclonal antibody, has been approved by the FDA for the treatment of SLE. We aimed to assess the effects of belimumab on demyelinating syndromes in patients with SLE. PATIENT CONCERNS: Six patients with demyelination in SLE who were managed at Traditional Chinese and Western Medicine Hospital of Wuhan from March 2021 to March 2023, who received belimumab ≥ 5 times, were enrolled. Ten age- and sex-matched SLE patients with noutneuropsychiatric systemic lupus erythematosus (NPSLE) and normal controls were recruited to analyze potential biomarkers. DIAGNOSES: All patients were diagnosed with SLE based on the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria or the 2019 EULAR/ACR classification criteria. All SLE patients with CNS demyelinating syndromes were diagnosed by rheumatologists, neurologists, and radiologists. INTERVENTIONS: These patients were administered belimumab combined with standard treatment (glucocorticoids and/or antimalarials and/or immunosuppressants [cyclophosphamide, mycophenolate, methotrexate, etc.]). OUTCOMES: Six patients were included in the study (100% female, mean [range] age at first demyelinating episode 42.8 [24-66] years). The most common extra-CNS features in these patients were rash, arthritis, alopecia, leukopenia, and hypocomplementemia. After Belimumab treatment, 3 of 6 (50%) patients achieved complete remission with decreased prednisone, 2 improvements, and 1 relapsed with uterine surgery. Compared with the baseline, 3.5 months post belimumab treatment, the disease activity score SLEDAI (21.5-5.5, P < .001), C3 and C4 increased, and extra-CNS symptoms improved rapidly. Moreover, The expression of lupus susceptibility gene PBX1 in CD19+ B cells was lowest in demyelinating syndromes with lupus patients compared with healthy volunteers and lupus patients without demyelination, and its relative expression negatively correlated with SLE disease activity. CONCLUSION: Belimumab could be an effective and safe option for the treatment of SLE demyelination. In addition, PBX1 might be a potential biomarker for the clinical diagnosis of lupus in patients with demyelinating syndrome.

The regulatory roles of MYC TFs in plant stamen development.

The stamen, as the male reproductive organ of flowering plants, plays a critical role in completing the life cycle of plants. MYC transcription factors are members of the bHLH IIIE subgroup and participate in a number of plant biological processes. In recent decades, a number of studies have confirmed that MYC transcription factors actively participate in the regulation of stamen development and have a critical impact on plant fertility. In this review, we summarized how MYC transcription factors play a role in regulating secondary thickening of the anther endothecium, the development and degradation of the tapetum, stomatal differentiation, and the dehydration of the anther epidermis. With regard to anther physiological metabolism, MYC transcription factors control dehydrin synthesis, ion and water transport, and carbohydrate metabolism to influence pollen viability. Additionally, MYCs participate in the JA signal transduction pathway, where they directly or indirectly control the development of stamens through the ET-JA, GA-JA, and ABA-JA pathways. By identifying the functions of MYCs during plant stamen development, it will help us to obtain a more comprehensive understanding not only on the molecular functions of this TF family but also the mechanisms underlying stamen development.

Association between dietary intake of α-tocopherol and cadmium related osteoporosis in population ≥ 50 years.

INTRODUCTION: To analyze the association between α-tocopherol intake and cadmium (Cd) exposure and osteoporosis in population ≥ 50 years. MATERIALS AND METHODS: Sociodemographic data, physical examination, and laboratory indicators including serum Cd level and dietary α-tocopherol intake of 8459 participants were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this cross-sectional study. The associations between α-tocopherol intake, serum Cd levels and osteoporosis were evaluated using univariate and multivariate logistic regression analyses, with the estimated value (ß), odds ratios (ORs) and 95% confidence intervals (CIs). We further explored the impact of α-tocopherol intake on Cd exposure and the bone mineral density (BMD) in total femur and femur neck. RESULTS: A total of 543 old adults suffered from osteoporosis. The serum Cd level (0.52 µg/L vs. 0.37 µg/L) and α-tocopherol intake (5.28 mg vs. 6.50 mg) were statistical different in osteoporosis group and non-osteoporosis group, respectively. High level of Cd exposure was related to the increased risk of osteoporosis [OR = 1.60, 95% CI (1.15-2.21)]. In the total femur, α-tocopherol intake may improve the loss of BMD that associated with Cd exposure [ß = - 0.047, P = 0.037]. Moreover, high α-tocopherol intake combined with low Cd exposure [OR = 0.54, 95% CI (0.36-0.81)] was linked to the decreased risk of osteoporosis comparing with low α-tocopherol intake combined with high Cd exposure. CONCLUSION: High α-tocopherol intake may improve the Cd-related osteoporosis and loss of BMD that could provide some dietary reference for prevention of osteoporosis in population ≥ 50 years old.

Distinct roles of ADIPOR1 and ADIPOR2: A pan-cancer analysis.

Introduction: AdipoR1 and AdipoR2 proteins, encoded by ADIPOR1 and ADIPOR2 genes respectively, are the receptors of adiponectin secrected by adipose tissue. Increasing studies have identified the vital role of adipose tissue in various diseases, including cancers. Hence, there is an urgent need to explore the roles of AdipoR1 and AdipoR2 in cancers. Methods: We conducted a comprehensive pan-cancer analysis for the roles of AdipoR1 and AdipoR2 via several public databases, including expression differences, prognostic value, and the correlations with tumor microenvironment, epigenetic modification, and drug sensitivity. Results: Both ADIPOR1 and ADIPOR2 genes are dysregulated in most cancers, but their genomic alteration frequencies are low. In addition, they are also correlated with the prognosis of some cancers. Although they are not strongly correlated with tumor mutation burden (TMB) or microsatellite instability (MSI), ADIPOR1/2 genes display a significant association with cancer stemness, tumor immune microenvironment, immune checkpoint genes (especially CD274 and NRP1), and drug sensitivity. Discussion: ADIPOR1 and ADIPOR2 play critical roles in diverse cancers, and it is a potential strategy to treat tumors through targeting ADIPOR1 and ADIPOR2.

Causal Effect of Higher Glycated Hemoglobin (HbA1c) Levels on Knee Osteoarthritis Risk: A Mendelian Randomization Study.

INTRODUCTION: The association between diabetes mellitus (DM) and risk of osteoarthritis (OA) is inconsistent based on published observational studies. This study aimed to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal link between glycated hemoglobin (HbA1c) level and OA risk. METHODS: Genome-wide association studies (GWAS) summary statistics were obtained from the publicly available Integrative Epidemiology Unit (IEU) OpenGWAS database. A series of screening processes were performed to select qualified instrumental single-nucleotide polymorphisms (SNPs) strongly related to exposure. The inverse-variance-weighted method, weighted-median method, and MR-Egger method were performed to ensure robust and reliable results. The MR-Egger intercept test, Cochran's Q test, and the leave-one-out sensitivity analysis were utilized to assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants for OA. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: MR analyses found a robust causal association of genetically determined HbA1c with knee OA (OR = 1.561; 95% CI 1.110-2.197; P = 0.011), but not with hip OA (OR = 1.073; 95% CI 0.674-1.710; P = 0.766) or overall OA (OR = 1.141; 95% CI 0.904-1.441; P = 0.804). Sensitivity analyses showed that there was a strong association between SNPs and HbA1c (F = 21.138), no evidence of heterogeneity (Q = 150.625, P = 0.402), and no potential SNPs affecting the causal link. CONCLUSION: Our MR study supported a causal effect of genetically increased HbA1c on knee OA risk.

Development of a ferroptosis-based model to predict prognosis, tumor microenvironment, and drug response for lung adenocarcinoma with weighted genes co-expression network analysis.

Objective: The goal of this study was to create a risk model based on the ferroptosis gene set that affects lung adenocarcinoma (LUAD) patients' prognosis and to investigate the potential underlying mechanisms. Material and Methods: A cohort of 482 LUAD patients from the TCGA database was used to develop the prognostic model. We picked the module genes from the ferroptosis gene set using weighted genes co-expression network analysis (WGCNA). The least absolute shrinkage and selection operator (LASSO) and univariate cox regression were used to screen the hub genes. Finally, the multivariate Cox analysis constructed a risk prediction score model. Three other cohorts of LUAD patients from the GEO database were included to validate the prediction ability of our model. Furthermore, the differentially expressed genes (DEG), immune infiltration, and drug sensitivity were analyzed. Results: An eight-gene-based prognostic model, including PIR, PEBP1, PPP1R13L, CA9, GLS2, DECR1, OTUB1, and YWHAE, was built. The patients from the TCGA database were classified into the high-RS and low-RS groups. The high-RS group was characterized by poor overall survival (OS) and less immune infiltration. Based on clinical traits, we separated the patients into various subgroups, and RS had remarkable prediction performance in each subgroup. The RS distribution analysis demonstrated that the RS was significantly associated with the stage of the LUAD patients. According to the study of immune cell infiltration in both groups, patients in the high-RS group had a lower abundance of immune cells, and less infiltration was associated with worse survival. Besides, we discovered that the high-RS group might not respond well to immune checkpoint inhibitors when we analyzed the gene expression of immune checkpoints. However, drug sensitivity analysis suggested that high-RS groups were more sensitive to common LUAD agents such as Afatinib, Erlotinib, Gefitinib, and Osimertinib. Conclusion: We constructed a novel and reliable ferroptosis-related model for LUAD patients, which was associated with prognosis, immune cell infiltration, and drug sensitivity, aiming to shed new light on the cancer biology and precision medicine.

Characterization of the immune cell infiltration landscape in myxofibrosarcoma to aid immunotherapy.

Myxofibrosarcoma (MFS) is a highly malignant subtype of soft tissue sarcoma, accounting for 5% of cases. Immunotherapy guided by immune cell infiltration (ICI) is reportedly a promising treatment strategy. Here, MFS samples (n = 104) from two independent databases were classified as ICI clusters A/B/C and gene clusters A/B/C. Then, a close relationship between ICI and gene clusters was established. We found that the features of these clusters were consistent with the characteristics of immune-inflamed tumors (cluster C), immune-desert tumors (cluster B), and immune-excluded tumors (cluster A). Moreover, cluster C was sensitive to immunotherapy. Finally, an independent ICI score was established to predict the therapeutic effect, which has prospects for application in guiding immunotherapy during clinical practice.

[The role of NAC transcription factors in flower development in plants].

Transcription factors, the proteins with special structures, can bind to specific sites and regulate specific expression of target genes. NAC (NAM, ATAF1/2, CUC1/2) transcription factors, unique to plants, are composed of a conserved N-terminal domain and a highly variable C-terminal transcriptional activation domain. NAC transcription factors are involved in plant growth and development, responses to biotic and abiotic stresses and other processes, playing a regulatory role in flower development. In this paper, we reviewed the studies about NAC transcription factors in terms of discovery, structure, and regulatory roles in anther development, other floral organ development and flowering time. This review will provide a theoretical basis for deciphering the regulatory mechanism and improving the regulatory network of NAC transcription factors in flower development.