Acupuncture Provides Short-Term Functional Improvements and Pain Relief for Patients After Knee Replacement Surgery: A Systematic Review and Meta-analysis.

The impact of acupuncture on knee function and pain intensity following knee replacement remains controversial. Therefore, we categorized the postsurgery recovery period into 3 phases: short-term (≤2 weeks), intermediate-term (2 weeks-3 months), and long-term (>3 months), and then assessed the effectiveness of acupuncture in improving function and alleviating pain at different stages following knee replacement. This meta-analysis included randomized controlled trials that compared acupuncture intervention with either no treatment or a sham group after knee replacement. Six databases were searched from inception to December 31, 2023, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and 2 Chinese databases (Chinese National Knowledge Infrastructure and WanFang Data). A total of 23 studies comprising 1,464 participants were included. Significant improvement of active range of motion was observed on day 7 and week 2 after operation. Lower pain intensity at rest was noted in patients receiving acupuncture in short-term periods after operation (12 hours, day 1, day 2, day 5, and week 2). A reduction in pain intensity during movement with acupuncture was observed on postoperative day 1 and day 7. Auricular acupuncture did not show not significant effectiveness in improving range of motion and pain intensity. For conventional acupuncture, the combination of distal and local point selection was found to be the most effective. Early application of acupuncture, in conjunction with physical therapy, starting before postoperative day 1 or day 2, was recommended. Further high-quality researches are warranted to validate the findings in this meta-analysis. PERSPECTIVE: This article demonstrates that acupuncture has short-term effects (≤2 weeks) on improving active range of motion and reducing pain during rest and during movement following knee replacement surgery. The findings support the early application of acupuncture in hospital settings after knee replacement. REGISTRATION ID: The study was registered on PROSPERO (CRD42024503479).

In vitro antioxidant and protective effects of the extract of Broussonetia papyrifera leaves on imiquimod-induced skin lesions in psoriasis-like mice.

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food. However, the treatment of psoriasis with the leaves of B. papyrifera has not been reported yet. The in vitro antioxidant activity of B. papyrifera leaf extract was investigated by DPPH, OH and ABTS assays. Furthermore, IMQ was used to induce a mouse psoriasis-like model and HE staining, enzyme-linked immunosorbent assay and biochemical kits were used to measure relevant pathological indexes. The results showed that the B. papyrifera leaf extract has certain antioxidant capacity in vitro, which was positively correlated with its concentration. In addition, the extract can not only improve IMQ-induced skin damage on the back of mice, inhibit TNF-α and IL-6 factor secretion, but also regulate activity of SOD and the serum levels of MDA. Its mechanism of action related to inhibiting the secretion of inflammatory factors and the regulation of oxidative stress in vivo.

High Cellular Internalization of Virus-Like Mesoporous Silica Nanoparticles Enhances Adaptive Antigen-Specific Immune Responses against Cancer.

Effective activation of an antigen-specific immune response hinges upon the intracellular delivery of cancer antigens to antigen-presenting cells (APCs), marking the initial stride in cancer vaccine development. Leveraging biomimetic topological morphology, we employed virus-like mesoporous silica nanoparticles (VMSNs) coloaded with antigens and toll-like receptor 9 (TLR9) agonists to craft a potent cancer vaccine. Our VMSNs could be efficiently internalized by APCs to a greater extent than their nonviral structured counterparts, thereby promoting the activation of APCs by upregulating the TLR9 pathway and cross-presenting ovalbumin (OVA) epitopes. In in vivo animal study, VMSN-based nanovaccines triggered substantial CD4+ and CD8+ lymphocyte populations in both lymph nodes and spleen while inducing the effector memory of adaptive T cells. Consequently, VMSN-based nanovaccines suppressed tumor progression and increased the survival rate of B16-OVA-bearing mice in both prophylactic and therapeutic studies. The combination of immune checkpoint blockade (ICB) with the VMSN-based nanovaccine has synergistic effects in significantly preventing tumor progression under therapeutic conditions. These findings highlight the potential of viral structure-mimicking mesoporous silica nanoparticles as promising candidates for antigen-delivering nanocarriers in vaccine development.

Comparative Efficacy of Deep Brain Stimulation to the Globus Pallidus Internus Versus the Subthalamic Nucleus in Parkinson's Disease.

Background: In recent years, the incidence of Parkinson's disease has gradually increased, and the application of dopamine drugs has been limited, so there is an urgent need to explore a more effective treatment method to treat Parkinson's disease effectively treated. Subthalamic nucleus-deep brain stimulation and globus pallidus internus-deep brain Subthalamic nucleus-deep brain stimulation and globus pallidus internus-deep brain stimulation are the two treatments for Parkinson's disease. However, there is no clear conclusion as to which of these two methods is more effective. Primary Study Objective: To compare the effects of deep brain stimulation in the globus pallidus internus and deep brain stimulation in the subthalamic nucleus combined with drugs for Parkinson's disease, respectively. Methods: In order to compare the motor function, neurological function, and activities of daily living scores, the incidence of fluctuations in isokinetic and motor symptoms, changes in medication doses, and the incidence of complications between the two groups, 52 patients treated with globus pallidus internus-deep brain stimulation and 52 patients treated with subthalamic nucleus-deep brain stimulation were included. Primary Outcome Measures: Using the Motor Function Examination scale of the Unified Parkinson's Disease Rating Scale, patients' motor function was evaluated prior to surgery, one month after surgery, three months after surgery, and six months following surgery. The Montreal Cognitive Assessment, the Mini-mental State Examination, and the Activity of Daily Living scale were used to evaluate patients' cognitive function before and three months after surgery. The patient's dose of medication and complications were also counted, among other things. Results: The Unified Parkinson's Disease Rating Scale-Ⅲ scores decreased, and the Montreal Cognitive Assessment, Mini-mental State Examination, and Activity of Daily Living scales increased in both groups after surgery, with no difference between the two groups (P > .05). Between the two groups, there was no difference in the frequency of allodynia and motor symptom variations (P > .05). Postoperatively, the Group globus pallidus internus experienced lower medication doses and a reduced incidence of complications than the Group subthalamic nucleus (P < .05). Conclusion: The effects of GPi-DBS and STN-DBS in treating PD are both more significant and there is no difference between them, but GPi-DBS reduces complications and medication dose, and has a higher safety profile, indicating that GPi-DBS is more suitable for clinical application and promotion. Future studies need to further explore the mechanism behind the reduction of complications and medication dose of GPi-DBS in Parkinson's disease, in order to provide better support for the clinical application of GPi-DBS.

Crystal Facets-Activity Correlation for Oxygen Evolution Reaction in Compositional Complex Alloys.

Compositional complex alloys, including high and medium-entropy alloys (HEAs/MEAs) have displayed significant potential as efficient electrocatalysts for the oxygen evolution reaction (OER), but their structure-activity relationship remains unclear. In particular, the basic question of which crystal facets are more active, especially considering the surface reconstructions, has yet to be answered. This study demonstrates that the lowest index {100} facets of FeCoNiCr MEAs exhibit the highest activity. The underlying mechanism associated with the {100} facet's low in-plane density, making it easier to surface reconstruction and form amorphous structures containing the true active species is uncovered. These results are validated by experiments on single crystals and polycrystal MEAs, as well as DFT calculations. The discoveries contribute to a fundamental comprehension of MEAs in electrocatalysis and offer physics-based strategies for developing electrocatalysts.

The effect and mechanism of palmar ginseng in type 2 diabetic cognitive impairment.

Objective: To investigate the therapeutic effect of palmar ginseng on cognitive impairment in rats with type 2 diabetes, evaluate its neuroprotective effects, and explore its underlying mechanism. Methods: A rat model of diabetic cognitive impairment (DCI) was established by feeding with homemade high-fat, high-sugar chow combined with intraperitoneal injection of streptozotocin (STZ). Rats were continually fed high-fat, high-sugar chow for 60 days after successful induction of the model. Palmar ginseng was administered via gavage. The Morris test was performed after 30 days of treatment. At the end of the test, blood samples were collected, and the activities of IL-6, IL-10, TNF-α, and IL-1ß in rat serum. Pathological changes in hippocampal tissues were observed by Haematoxylin-eosin (HE) staining of the brain, activation of microglia in hippocampal tissues was detected by immunofluorescence, and the expression of PI3K/Akt/mTOR and JAK2/STAT3 proteins in the hippocampal tissues by Western blot. Results: During the administration of palmar Ginseng, the body weight and blood glucose levels of DCI rats were measured weekly, with results showing that Palmar Ginseng effectively reduced blood glucose levels and body weight of DCI rats. Behavioural tests in the water maze indicated that palmar ginseng effectively improved the learning and memory ability of DCI rats. HE and immunofluorescence staining showed that palmar ginseng improved DCI in rats, ameliorated hippocampal neuronal damage, and improved microglial activation. ELISA showed that palmar ginseng significantly reduced the expression of pro-inflammatory factors in the serum of DCI rats. Increased expression of anti-inflammatory factors was observed, and Western blot analysis showed that Palmar Ginseng regulated PI3K/Akt/mTOR and JAK2/STAT3 protein expression, promoted the phosphorylation of PI3K/Akt/mTOR, and inhibited JAK2/STAT3 protein phosphorylation in rat hippocampal tissues as well as in BV2 cells. Conclusions: Palmar ginseng may improve the onset and development of DCI by upregulating the phosphorylation of proteins in the PI3K/Akt/mTOR pathway.

Machine learning-based radiomics for predicting outcomes in cervical cancer patients undergoing concurrent chemoradiotherapy.

PURPOSES: To investigate the value of machine learning-based radiomics for predicting disease-free survival (DFS) and overall survival (OS) undergoing concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC). MATERIALS AND METHODS: In this multicentre study, 700 patients with IB2-IVA cervical cancer who underwent CCRT with ongoing follow-up were retrospectively analyzed. Three-dimensional radiomics features of primary lesions and its surrounding 5 mm region in T2WI sequences were collected. Six machine learning methods were used to construct the optimal radiomics model for accurate prediction of DFS and OS after CCRT in LACC patients. Eventually, TCGA and GEO databases were used to explore the mechanisms of radiomics in predicting the progression and survival of cervical cancer. This study adhered CLEAR for reporting and its quality was assessed using RQS and METRICS. RESULTS: In the prediction of DFS, the RSF model combined tumor and peritumor radiomics demonstrated the best predictive efficacy, with the AUC for predicting 1-year, 3-year, and 5-year DFS in the training, validation, and test sets of 0.986, 0.989, 0.990, and 0.884, 0.838, 0.823, and 0.829, 0.809, 0.841, respectively. In the prediction of OS, the GBM model best performer, with AUC of 0.999, 0.995, 0.978, and 0.981, 0.975, 0.837, and 0.904, 0.860, 0.905. Differential genes in TCGA and GEO suggest that the prediction of radiomics model may be associated with KDELR2 and HK2. CONCLUSION: Machine learning-based radiomics models help to predict DFS and OS after CCRT in LACC patients, and the combination of tumor and peritumor information has higher predictive efficacy, which can provide a reliable basis for therapeutic decision-making in cervical cancer patients.

Self-Assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis.

Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI is quite limited due to the low efficiency and poor kidney-targeting ability. Herein, a novel self-assembling peptide nanoparticle with specific p38-inhibiting activity is constructed, which linked mitogen-activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell-penetrating TAT sequence, ultimately self-assembling into TAT-MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia-reperfusion injury (IRI)-induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis-inducing capacity and synergistic potent antioxidant property in AKI. The findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS-scavenging, and ferroptosis-mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

Cast versus Kirschner wire fixation in type II paediatric phalangeal neck fractures.

PURPOSE: To compare the outcomes of type II pediatric phalangeal neck fractures (PPNFs) treated with closed reduction and cast immobilization (CRCI) versus closed reduction percutaneous pinning (CRPP), and evaluated the clinical efficacy of conservative versus surgical treatment of type II PPNFs via meta-analysis. METHODS: Patients aged ≤ 14 years with type II PPNFs were divided into conservative (CRCI) and operative (CRPP) groups. Radiographs measured angulation and translation; hand function was assessed with total active range of motion (TAM) and Quick-DASH. Complication rates were also compared between the groups. A meta-analysis of conservative versus operative treatment confirmed the clinical results. Statistical analysis was performed using SPSS 26.0 and R studio 3.0 with two-tailed, chi-squared, and Mann-Whitney U or t-tests, P < 0.05. Meta-analysis used fixed or random effects models, calculating mean differences and odds ratios for outcomes, and assessing heterogeneity with I2 and Q tests. RESULTS: Final angulation (3.4° ± 3.7° and 4.9° ± 5.4° vs. 3.6° ± 3.7° and 4.2° ± 4.3°) and displacement (6.3% ± 5.8% and 5.7% ± 4.7% vs. 5.8% ± 5.5% and 3.2% ± 4.2%) in the coronal and sagittal planes were not different statistically between the conservative and surgical groups (P > 0.05), but improved significantly compared to preoperative values (P < 0.05). Although Quick-DASH scores were comparable in both groups (P = 0.105), conservatively treated patients had a significantly better TAM at the last follow-up visit (P = 0.005). The complication rates were 24.2% and 41.7% in the surgical and conservatively treated groups respectively (P = 0.162). However, the latter primarily experienced imaging-related complications, whereas the former experienced functional complications (P = 0.046). Our meta-analysis (n = 181 patients) also showed comparable functional (P = 0.49) and radiographic (P = 0.59) outcomes and complication rates (P = 0.21) between the surgical (94 patients) and conservative (87 patients) groups. CONCLUSIONS: Conservative and surgical treatments are both reliable and safe approaches for managing type II PPNF in children. However, conservatively treated patients generally experience similar radiographic outcomes, lower complication rates, and better functional outcomes than surgically treated ones.

A state-of-art review on the redox activity of persistent free radicals in biochar.

Biochar-bound persistent free radicals (biochar-PFRs) attract much attention because they can directly or indirectly mediate the transformation of contaminants in large-scale wastewater treatment processes. Despite this, a comprehensive top-down understanding of the redox activity of biochar-PFRs, particularly consumption and regeneration mechanisms, as well as challenges in redox activity assessment, is still lacking. To tackle this challenge, this review outlines the identification and determination methods of biochar-PFRs, which serve as a prerequisite for assessing the redox activity of biochar-PFRs. Recent developments concerning biochar-PFRs are discussed, with a main emphasis on the reaction mechanisms (both non-free radical and free radical pathways) and their effectiveness in removing contaminants. Importantly, the review delves into the mechanism of biochar-PFRs regeneration, triggered by metal cations, reactive oxygen species, and ultraviolet radiations. Furthermore, this review thoroughly explores the dilemma in appraising the redox activity of biochar-PFRs. Components with unpaired electrons (particular defects and metal ions) interfere with biochar-PFRs signals in electron paramagnetic resonance spectra. Scavengers and extractants of biochar-PFRs also inevitably modify the active ingredients of biochar. Based on these analyses, a practical strategy is proposed to precisely determine the redox activity of biochar-PFRs. Finally, the review concludes by presenting current gaps in knowledge and offering suggestions for future research. This comprehensive examination aims to provide new and significant insights into the redox activity of biochar-PFRs.

Effectivenss of electroacupuncture for skeletal muscle pain in Parkinson's disease: a Clinical randomized controlled trial.

OBJECTIVE: To explore the effect of electroacupuncture on skeletal muscle pain in Parkinson's disease (PD). METHODS: A single-center randomized controlled trial was conducted with sixty patients with Parkinson's disease with skeletal muscle pain were randomly divided into electroacupuncture group and sham acupuncture control group with 30 patients each. The electric acupuncture group was treated with electric acupuncture, while the control group was treated with Park needle pseudoacupuncture. Both groups were treated 5 times a week for a total of 4 weeks, and both groups completed 20 treatments. King's Parkinson's Pain Scale (KPPS) and visual analog scale (VAS) were used before and after treatment to evaluate the pain degree of patients. Real-time shear wave elastography (SWE) and modified Ashworth score (MAS) were used to evaluate the changes of muscle tone. Parkinson's comprehensive Score Scale (MDS-UPDRS, including UPDRSⅡ and UPDRS Ⅲ) was used to evaluate exercise ability. Hamilton Depression Scale (HAMD) score was used to evaluate the emotional changes of patients. Spearman correlation analysis was used to explore the correlation between pain degree and muscle tone, exercise ability and emotion. RESULTS: During the study, one case fell off in the control group, and 30 cases were eventually included in the analysis and treatment group and 29 cases in the control group. After treatment, Young's modulus of biceps and quadriceps and shear wave velocity of biceps were decreased in electroacupuncture group compared with before treatment, while KPPS score, VAS score, UPDRSⅡ, UPDRS Ⅲ and modified Ashworth score were decreased, with statistical significance (P < 0.05). There was no statistical significance in control group (P > 0.05). After treatment, KPPS score, VAS score, UPDRSⅡ and UPDRS Ⅲ, MAS, HAMD score, Young's modulus of biceps and shear wave velocity in electroacupuncture group were significantly lower than those in control group (P < 0.05). Spearman correlation analysis showed that KPPS score was positively correlated with UPDRS Ⅲ (r = 0.414, P < 0.05). KPPS score was positively correlated with HAMD score (r = 0.576, P < 0.01). CONCLUSION: Electroacupuncture therapy can effectively improve skeletal muscle pain in patients with Parkinson's disease, reduce the muscle hardness of patients, improve patients' daily life ability, and improve patients' emotional disorders. The degree of skeletal muscle pain in PD patients is correlated with motor ability and emotional disorders, but there is no significant correlation between the degree of skeletal muscle pain and the muscle tone of PD patients.

Appendicitis combined with Meckel's diverticulum obstruction, perforation, and inflammation in children: Three case reports.

BACKGROUND: Meckel's diverticulum is a common congenital malformation of the small intestine, with the three most common complications being obstruction, perforation, and inflammation. To date, only a few cases have been reported worldwide. In children, the clinical symptoms are similar to appendicitis. As most of the imaging features are nonspecific, the preoperative diagnosis is not precise. In addition, the clinical characteristics are highly similar to pediatric acute appendicitis, thus special attention is necessary to distinguish Meckel's diverticulum from pediatric appendicitis. Patients with poor disease control should undergo laparoscopic exploration to avoid serious complications, including intestinal necrosis, intestinal perforation and gastrointestinal bleeding. CASE SUMMARY: This report presents three cases of appendicitis in children combined with intestinal obstruction, which was caused by fibrous bands (ligaments) arising from the top part of Meckel's diverticulum, diverticular perforation, and diverticular inflammation. All three patients, aged 11-12 years, had acute appendicitis as their initial clinical presentation. All were treated by laparoscopic surgery with a favorable outcome. A complete dataset including clinical presentation, diagnostic imaging, surgical information, and histopathologic findings was also provided. CONCLUSION: Preoperative diagnosis of Meckel's diverticulum and its complications is challenging because its clinical signs and complications are similar to those of appendicitis in children. Laparoscopy combined with laparotomy is useful for diagnosis and treatment.

Low-dose deoxynivalenol exposure inhibits hepatic mitophagy and hesperidin reverses this phenomenon by activating SIRT1.

Deoxynivalenol (DON) is by far the most common mycotoxin contaminating cereal foods and feeds. Furthermore, cleaning up DON from contaminated cereal items is challenging. Low-dose DON consumption poses a danger to humans and agricultural animals. The benefits of hesperidin (HDN) include liver protection, anti-oxidative stress, nontoxicity, and a broad range of sources. The study used immunoblotting, immunofluorescence, and transmission electron microscopy to identify factors associated with mitophagy in vitro and in vivo. We demonstrated that low-dose DON exposure inhibited mitophagy in the liver tissue of mice. SIRT1 was a crucial regulator of mitophagy. Moreover, DON stimulated the dephosphorylation of SIRT1 and the acetylation-regulated FOXO3 protein, which resulted in the transcriptional inhibition of FOXO3-driven BNIP3 and compromised the stability of the PINK1 protein mediated by BNIP3. Moreover, HDN's effect was comparable to that of a SIRT1 agonist, which led to a significant decrease in the level of mitophagy inhibition caused by low-dose DON exposure. When combined, these findings suggested that HDN might be a useful treatment approach for liver damage brought on by low-dose DON exposure. Above all, this research will offer fresh perspectives on a viable approach that will encourage further research into risk reduction initiatives for low-dose DON exposure.

The efficacy and safety of hydroxychloroquine versus leflunomide in patients with IgA nephropathy: a single-center experience.

PURPOSE: To date, our understanding of IgA nephropathy (IgAN) pathophysiology has remained incomplete; therefore, treatment remains largely empiric, and the efficacy and safety of immunosuppressants remain controversial. We aimed to assess the efficacy and safety of hydroxychloroquine and leflunomide therapy in a retrospective cohort of patients with IgAN. METHODS: We screened the IgAN registration database in our department, and a total of 159 kidney patients with biopsy-confirmed IgAN were enrolled, with 57 patients receiving hydroxychloroquine plus a renin-angiotensin system inhibitor (hydroxychloroquine group), 52 patients receiving leflunomide plus a renin-angiotensin system inhibitor (leflunomide group), and 50 patients receiving only a renin-angiotensin system inhibitor (renin-angiotensin system inhibitor-only group). Changes in proteinuria, hematuria, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were analyzed during the follow-up period. RESULTS: At the end of 6-month follow-up, proteinuria significantly decreased by 70.36 (57.54, 79.33)%, 57.29 (46.79, 67.29)% and 41.20 (25.76, 48.94)% in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, respectively, compared to baseline (all P values < 0.001). Hematuria significantly decreased by 71.07 (56.48, 82.47)% in the leflunomide group (P < 0.001). The eGFR improved by 3.72 ± 2.97%, 3.16 ± 2.00% and 1.91 ± 2.41%, respectively, in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, but without statistical significance. No serious adverse events occurred during the follow-up period. CONCLUSION: Both hydroxychloroquine combined with a renin-angiotensin system inhibitor and leflunomide combined with a renin-angiotensin system inhibitor were more effective than a renin-angiotensin system inhibitor alone in improving proteinuria in IgAN patients. Hydroxychloroquine was more effective in reducing proteinuria, and leflunomide showed superiority in reducing hematuria. Our results need to be verified in large-scale randomized controlled trials.

Conduction system pacing for ventricular pacing requirement is feasible and effective on patients with hypertrophic cardiomyopathy and cardiac dysfunction.

Objective: We aimed to evaluate the feasibility and safety of his-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with hypertrophic cardiomyopathy (HCM) and heart failure (HF). Methods: Patients with HF and interventricular septal thickness (IVST) ≥ 13 mm resulted from HCM, who accepted conduction system pacing (CSP) with a percentage of ventricular pacing > 40% from May 2018 to April 2022 were consecutively enrolled in our center. LBBP was preferred and HBP was the alternative therapy unless IVST ≥ 16 mm or LBBP failed, whereas LBBP would be the alternative therapy if HBP failed in patients with IVST ≥ 16 mm. All patients were followed up for at least one year. Data including clinical, echocardiographic parameters and electrocardiogram measurements, were collected and evaluated in patients with and without left ventricular ejection fraction (LVEF) < 50%. Results: A total of 27 patients (65.93 ± 9.09 years old) were enrolled and only 3 patients failed in CSP (11.11%) via LBBP (6/13) and HBP (18/21) procedures. LVEF (P = 0.521), left ventricular end-diastolic diameter (LVEDD) (P = 0.816), and QRS duration (P = 0.928) did not worsen after CSP, and left atrial diameter (LAD) (49.58 ± 8.99 mm vs.47.04 ± 9.82 mm, P = 0.045) tended to improve slightly after 19.19 ± 7.71 months follow-up. Of note, LVEF (39.22%±7.51% vs. 45.22%±9.59%, P = 0.015), LVEDD (52.11 ± 10.10 mm vs. 48.33 ± 9.07 mm, P = 0.037), LAD (50.33 ± 8.93 mm vs. 46.11 ± 5.97 mm, P = 0.013) and New York Heart Association (NYHA) grade (2.67 ± 0.5 vs. 1.38 ± 1.02, P = 0.029) improved in 9 patients with LVEF < 50%, whereas LVEF (P = 0.372), LVEDD (P = 0.665), LAD (P = 0.093) and NYHA grade (P = 0.452) did not deteriorate in patients with preserved ejection fraction. Conclusion: CSP was safe and feasible in patients with HCM and cardiac dysfunction, and did not worsen cardiac performance especially in patients with LVEF < 50%. HBP might be an effective alternative to LBBP in patients with significantly thickened interventricular septum.

[Adsorption Characteristics of Tetracycline by CuFeO2-modified Biochar].

CuFeO2-modified biochars were prepared through co-precipitation and hydrothermal methods, and the composites had high efficiency removal for tetracycline (TC) from water. The CuFeO2-modified biochar with a 2:1 mass ratio of CuFeO2 to BC450 (CuFeO2/BC450=2:1) demonstrated the best adsorption performance. The kinetic process of TC adsorption by CuFeO2/BC450=2:1 was well fitted with the intraparticle diffusion model, suggesting that the adsorption process was controlled by film and pore diffusion. Under the condition of neutral pH and 298 K, the maximum adsorption capacity of the Langmuir model of CuFeO2/BC450=2:1 was 82.8 mg·g-1, which was much greater than that of BC450 (13.7 mg·g-1) and CuFeO2(14.8 mg·g-1). The thermodynamic data suggested that TC sorption onto CuFeO2/BC450=2:1 was a spontaneous and endothermic process. The removal of TC by CuFeO2/BC450=2:1 increased first and then decreased with increasing pH, and the maximum adsorption occurred under the neutral condition. The strong adsorption of TC by CuFeO2/BC450=2:1 could be attributed to better porosity, larger specific surface area, and more active sites (e.g., functional groups and charged surfaces). This work provided an efficient magnetic adsorbent for removing antibiotics.

Population Pharmacokinetics and Exposure-Response with Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma: Results From MajesTEC-1.

BACKGROUND: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, is approved in patients with relapsed/refractory multiple myeloma (RRMM) who have previously received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. OBJECTIVE: We report the population pharmacokinetics of teclistamab administered intravenously and subcutaneously (SC) and exposure-response relationships from the phase I/II, first-in-human, open-label, multicenter MajesTEC-1 study. METHODS: Phase I of MajesTEC-1 consisted of dose escalation and expansion at the recommended phase II dose (RP2D; 1.5 mg/kg SC weekly, preceded by step-up doses of 0.06 and 0.3 mg/kg); phase II investigated the efficacy of teclistamab RP2D in patients with RRMM. Population pharmacokinetics and the impact of covariates on teclistamab systemic exposure were assessed using a 2-compartment model with first-order absorption for SC and parallel time-independent and time-dependent elimination pathways. Exposure-response analyses were conducted, including overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and the incidence of grade ≥ 3 anemia, neutropenia, lymphopenia, leukopenia, thrombocytopenia, and infection. RESULTS: In total, 4840 measurable serum concentration samples from 338 pharmacokinetics-evaluable patients who received teclistamab were analyzed. The typical population value of time-independent and time-dependent clearance were 0.449 L/day and 0.547 L/day, respectively. The time-dependent clearance decreased rapidly to < 10% after 8 weeks of teclistamab treatment. Patients who discontinue teclistamab after the 13th dose are expected to have a 50% reduction from Cmax in teclistamab concentration at a median (5th to 95th percentile) time of 15 days (7-33 days) after Tmax and a 97% reduction from Cmax in teclistamab concentration at a median time of 69 days (32-163 days) after Tmax. Body weight, multiple myeloma type (immunoglobulin G vs non-immunoglobulin G), and International Staging System (ISS) stage (II vs I and III vs I) were statistically significant covariates on teclistamab pharmacokinetics; however, these covariates had no clinically relevant effect on the efficacy of teclistamab at the RP2D. Across all doses, ORR approached a plateau at the concentration range associated with RP2D, and in patients who received the RP2D, a flat exposure-response curve was observed. No apparent relationship was observed between DoR, PFS, OS, and the incidence of grade ≥3 adverse events across the predicted exposure quartiles. CONCLUSION: Body weight, myeloma type, and ISS stage impacted systemic teclistamab exposure without any clinically relevant effect on efficacy. The exposure-response analyses for ORR showed a positive trend with increasing teclistamab systemic exposure, with a plateau at the RP2D, and there was no apparent exposure-response trend for safety or other efficacy endpoints. These analyses support the RP2D of teclistamab in patients with RRMM. CLINICAL TRIAL REGISTRATION: NCT03145181 (phase I, 09 May 2017); NCT04557098 (phase II, 21 September 2020).