Crystal-Site Engineering of Novel Na3KMg7(PO4)6-x(BO3)x:Eu2+ Phosphors for Full-Spectrum Lighting.

The "cyan gap" is the bottleneck problem in violet-driven full-spectrum white-light-emitting diodes (wLEDs) in healthy lighting. Accordingly, we develop a novel broadband-blue-cyan emission Na3KMg7(PO4)6-x(BO3)x:Eu2+ (NKMPB:Eu2+) phosphor via crystal-site engineering. This phosphor is derived from the Na3KMg7(PO4)6:Eu2+ phosphor, which shows desired abundant cyan emissive components. A comparative study is conducted to reveal the microstructure-property relationship and the key influential factors to its spectrum distribution. It can be found that the introduced (BO3)3- units can manipulate the site-selective occupation of Eu2+ activators, asymmetrically broadening the emission spectrum in NKMPB:Eu2+. Considering detailed luminescence performance analysis and the density functional theory calculations, a new substitution pathway of Eu2+ is created by substituting (PO4)3- with (BO3)3- units, making partial Eu2+ ions enter the Mg2+ (CN = 5, CN = 6) crystallographic sites, and yielding an extra emission band at 600 nm (16667 cm-1) and especially 501 nm (19960 cm-1). Meanwhile, a high-color-quality full-spectrum-emitting wLEDs was fabricated, upon 100 mA forward-bias current driven. Due to the achieved extra cyan emissive components of NKMPB:Eu2+, the constructed NKMPB:Eu2+-based wLEDs show better color rendering ability (∼90.9) than that of Na3KMg7(PO4)6:Eu2+-based wLEDs (∼86.3), and also demonstrate its great potential in full-spectrum healthy lighting.

The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real-world, multicenter, retrospective study.

BACKGROUND: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated. METHODS: This is a real-world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370). Overall survival (OS) and time to treatment failure (TTF) from the time of ICI initiation were compared among patients in subgroups of interest by unadjusted and 12-week landmark sensitivity-adjusted analyses. The association of irAEs and their management with OS and TTF were evaluated using univariate and multivariable Cox proportional hazards regression models. RESULTS: Overall, irAEs of any grade and of grade ≥3 occurred in 57% and 23% of patients, respectively. Thirty-seven percent of patients received steroids, and 3% received other ISAs. Median OS was longest among patients receiving both (not reached [NR]), shorter among those receiving only systemic steroids (SSs) (84.2 months; 95% CI, 40.2 months to NR), and shortest among those who did not experience irAEs (10.3 months; 95% CI, 6-20.1 months) (p < .001). Longer OS was significantly associated with the occurrence of irAEs and the use of SSs with or without ISAs upon multivariable-adjusted analysis (p < .001). Similar results were noted with anti-programmed death 1 (PD-1) monotherapy and combination anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy, and with 12-week landmark sensitivity analysis (p = .01). CONCLUSIONS: These findings in patients with melanoma who were treated with ICIs suggest that the use of SSs or ISAs for the management of irAEs is not associated with inferior disease outcomes, which supports the use of these agents when necessary.

HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane.

PURPOSE: To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). METHODS: Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). RESULTS: Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. CONCLUSION: Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids.

BACKGROUND: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. METHODS: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. RESULTS: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. CONCLUSIONS: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

Hematologic safety of palbociclib in combination with endocrine therapy in patients with benign ethnic neutropenia and advanced breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, are approved to treat hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and are associated with hematologic toxicity. African American women, who are underrepresented in CDK4/6 inhibitor clinical trials, may experience worse neutropenia because of benign ethnic neutropenia. The authors specifically investigated the hematologic safety of palbociclib in African American women with HR-positive/HER2-negative ABC. METHODS: PALINA was a single-arm, open-label, investigator-initiated study of palbociclib (125 mg daily; 21 days on and 7 days off) plus endocrine therapy (ET) in African American women who had HR-positive/HER2-negative ABC and a baseline absolute neutrophil count ≥1000/mm3 (ClinicalTrials.gov identifier NCT02692755). The primary outcome was the proportion of patients who completed 12 months of therapy without experiencing febrile neutropenia or treatment discontinuation because of neutropenia. Single nucleotide polymorphism analysis was used to assess Duffy polymorphism status. RESULTS: Thirty-five patients received ≥1 dose of palbociclib plus ET; 19 had a Duffy null polymorphism (cytosine/cytosine). There were no reports of febrile neutropenia or permanent study discontinuation because of neutropenia. Significantly more patients with the Duffy null versus the wild-type variant had grade 3 and 4 neutropenia (72.2% vs 23.1%; P = .029) and required a palbociclib dose reduction (55.6% vs 7.7%; P = .008). Patients with the Duffy null versus the wild-type variant had lower overall relative dose intensity (mean ± SD, 81.89% ± 15.87 and 95.67% ± 5.89, respectively; P = .0026) and a lower clinical benefit rate (66.7% and 84.6%, respectively). CONCLUSIONS: These findings suggest that palbociclib is well tolerated in African American women with HR-positive/HER2-negative ABC. Duffy null status may affect the incidence of grade 3 neutropenia, dose intensity, and possibly clinical benefit.

Molecular mechanism of water reorientational slowing down in concentrated ionic solutions.

Water dynamics in concentrated ionic solutions plays an important role in a number of material and energy conversion processes such as the charge transfer at the electrolyte-electrode interface in aqueous rechargeable ion batteries. One long-standing puzzle is that all electrolytes, regardless of their "structure-making/breaking" nature, make water rotate slower at high concentrations. To understand this effect, we present a theoretical simulation study of the reorientational motion of water molecules in different ionic solutions. Using an extended Ivanov model, water rotation is decomposed into contributions from large-amplitude angular jumps and a slower frame motion which was studied in a coarse-grained manner. Bearing a certain resemblance to water rotation near large biological molecules, the general deceleration is found to be largely due to the coupling of the slow, collective component of water rotation with the motion of large hydrated ion clusters ubiquitously existing in the concentrated ionic solutions. This finding is at variance with the intuitive expectation that the slowing down is caused by the change in fast, single-molecular water hydrogen bond switching adjacent to the ions.

High Thermoelectric Performance of New Rhombohedral Phase of GeSe stabilized through Alloying with AgSbSe2.

GeSe is a IV-VI semiconductor, like the excellent thermoelectric materials PbTe and SnSe. Orthorhombic GeSe has been predicted theoretically to have good thermoelectric performance but is difficult to dope experimentally. Like PbTe, rhombohedral GeTe has a multivalley band structure, which is ideal for thermoelectrics and also promotes the formation of Ge vacancies to provide enough carriers for electrical transport. Herein, we investigate the thermoelectric properties of GeSe alloyed with AgSbSe2 , which stabilizes a new rhombohedral structure with higher symmetry that leads to a multivalley Fermi surface and a dramatic increase in carrier concentration. The zT of GeAg0.2 Sb0.2 Se1.4 reaches 0.86 at 710 K, which is 18 times higher than that of pristine GeSe and over four times higher than doped orthorhombic GeSe. Our results open a new avenue towards developing novel thermoelectric materials through crystal phase engineering using a strategy of entropy stabilization of high-symmetry alloys.

Low frequency 2D Raman-THz spectroscopy of ionic solution: A simulation study.

The 2D Raman-THz spectrum of the MgCl2 solution was simulated using the molecular dynamics simulation and the stability matrix method and compared with that of the pure water. The 2D Raman-THz signal provides more information on the ion effects on the collective water motion than the conventional 1D signal. The presence of MgCl2 suppresses the cross peak of water between the hydrogen bond bending and the other intermolecular vibrational mode, which clearly illustrates that the water hydrogen bending motion is affected by the confining effect of the ions. Our theoretical work thus demonstrates that the 2D Raman-THz technique can become a valuable nonlinear vibrational probe for the molecular dynamics in the ionic solutions.

Discriminating trpzip2 and trpzip4 peptides' folding landscape using the two-dimensional infrared spectroscopy: a simulation study.

We analyzed, based on the theoretical spectroscopic modeling, how the differences in the folding landscapes of two ß-hairpin peptides trpzip2 and trpzip4 are reflected in their thermal unfolding infrared measurements. The isotope-edited equilibrium FTIR and two dimensional infrared spectra of the two peptides were calculated, using the nonlinear exciton propagation method, at a series of temperatures. The spectra calculations were based on the configuration distributions generated using the GB(OBC) implicit solvent MD simulation and the integrated tempering sampling technique. Conformational analysis revealed the different local thermal stabilities for these two peptides, which suggested the different folding landscapes. Our study further suggested that the ellipticities of the isotope peaks in the coherent IR signals are more sensitive to these local stability differences compared with other spectral features such as the peak intensities. Our technique can thus be combined with the relevant experimental measurements to achieve a better understanding of the peptide folding behaviors.

Chinese Medicine Supplementing Qi and Activating Blood Circulation Relieves the Progression of Diabetic Cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) is the leading cause of diabetic death as the final occurrence of heart failure and arrhythmia. Traditional Chinese medicine is usually used to treat various diseases including diabetes. OBJECTIVE: This study sought to investigate the effects of Traditional Chinese medicine supplementing Qi and activating blood circulation (SAC) in DCM. METHODS: After the construction of the DCM model by streptozotocin (STZ) injection and high glucose/fat diet feeding, rats were administered intragastrically with SAC. Then, cardiac systolic/diastolic function was evaluated by detecting left ventricular systolic pressure (LVSP), maximal rate of left ventricular pressure rise (+LVdp/dtmax), and fall (-LVdp/dtmax), heart rate (HR), left ventricular ejection fraction (EF), LV fractional shortening (FS) and left ventricular end-diastolic pressure (LVEDP). Masson's and TUNEL staining were used to assess fibrosis and cardiomyocyte apoptosis. RESULTS: DCM rats exhibited impaired cardiac systolic/diastolic function manifested by decreasing LVSP, + LVdp/dtmax, -LVdp/dtmax, HR, EF and FS, and increasing LVEDP. Intriguingly, traditional Chinese medicine SAC alleviated the above-mentioned symptoms, indicating a potential role in improving cardiac function. Masson's staining substantiated that SAC antagonized the increased collagen deposition and interstitial fibrosis area and the elevations in protein expression of fibrosisrelated collagen I and fibronectin in heart tissues of DCM rats. Furthermore, TUNEL staining confirmed that traditional Chinese medicine SAC also attenuated cardiomyocyte apoptosis in DCM rats. Mechanically, DCM rats showed the aberrant activation of the TGF-ß/Smad signaling, which was inhibited after SAC. CONCLUSION: SAC may exert cardiac protective efficacy in DCM rats via the TGF-ß/Smad signaling, indicating a new promising therapeutic approach for DCM.

Highly Bright and Stable Lead-Free Double Perovskite White Light-Emitting Diodes.

Lead-free double perovskites (DPs) are emerging highly stable emitters with efficient broadband self-trapped exciton (STE) photoluminescence (PL), but their low electroluminescent (EL) efficiency is a critical shortcoming. This work promotes the external quantum efficiency (EQE) and luminance of DP-based white light-emitting diode (wLED) with a normal device structure to 0.76% and 2793 cd m-2 via two modifications: This work prevents the formation of adverse metallic silver, spatially confined STE, and lowers local site symmetry in Cs2 Na0.4 Ag0.6 In0.97 Bi0.03 Cl6 DP by terbium doping; and this work develops a guest-host strategy to improve film morphology, reduce defect density, and increase carrier mobility. These alterations cause substantial increase in STE radiative recombination and charge injection efficiency of perovskite layer. Finally, pure white EL with ideal color coordinates of (0.328, 0.329) and a record-breaking optoelectronic performance is achieved by introducing additional green carbon dots in LED to fill the deficient green component.

Ultrasound-activated piezo-hot carriers trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections.

Implant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose a multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis to amplify the efficacy of sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine and copper, the ultrasound-activated piezo-hot carriers transfer easily to copper by polydopamine. It boosts reactive oxygen species production by piezoelectrics, and facilitates the interconversion between Cu2+ and Cu+ to promote hydroxyl radical generation via Cu+ -catalyzed chemodynamic reactions. Finally, the elevated reactive oxygen species cause bacterial membrane structure loosening and DNA damage. Transcriptomics and metabolomics analysis reveal that intracellular copper overload restricts the tricarboxylic acid cycle, promoting bacterial cuproptosis-like death. Therefore, the polyetherketoneketone scaffold engineered with the designed nanoreactor shows excellent antibacterial performance with ultrasound stimulation and promotes angiogenesis and osteogenesis on-demand in vivo.

Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Modeling the thermal unfolding 2DIR spectra of a ß-hairpin peptide based on the implicit solvent MD simulation.

We simulated the equilibrium isotope-edited FTIR and 2DIR spectra of a ß-hairpin peptide trpzip2 at a series of temperatures. The simulation was based on the configuration distributions generated using the GB(OBC) implicit solvent model and the integrated tempering sampling (ITS) technique. A soaking procedure was adapted to generate the peptide in explicit solvent configurations for the spectroscopy calculations. The nonlinear exciton propagation (NEP) method was then used to calculate the spectra. Agreeing with the experiments, the intensities and ellipticities of the isotope-shifted peaks in our simulated signals have the site-specific temperature dependences, which suggest the inhomogeneous local thermal stabilities along the peptide chain. Our simulation thus proposes a cost-effective means to understand a peptide's conformational change and related IR spectra across its thermal unfolding transition.

Seven-photon absorption from Na+/Bi3+-alloyed Cs2AgInCl6 perovskites.

Nonlinear multi-phonon (2-7) absorption in the Na+/Bi3+-alloyed Cs2AgInCl6 lead-free double perovskites with ∼100% photoluminescence quantum yield and superior stability is observed for the first time, which can be pumped by a femtosecond laser in a wide spectral range (800-2600 nm). First-principles calculations verify that the parity-forbidden transition from the valence band maximum and conduction band minimum (at the Γ point) is not broken by Na+/Bi3+ doping, and strong optical band-to-band absorption occurs at the L&X points. Time-resolved emission spectra evidence that single-photon and multi-photon pumping leads to the same self-trapped exciton transition and high-order nonlinear absorption will not induce a remarkable thermal effect. Finally, we demonstrate that the Cs2Na0.4Ag0.6In0.99Bi0.01Cl6 DP shows great potential for next-generation wavelength-selective and highly sensitive multiphoton imaging applications.

Patterns of Screening Mammography and Breast MRI During the COVID-19 Pandemic: A Retrospective, Chart-Review Study.

Objective: This study examined patterns of breast cancer screening during the COVID-19 pandemic. Methods: This retrospective study was approved by the Georgetown University IRB. Review of electronic medical records identified screening mammograms and breast MRIs between March 13, 2018 and December 31, 2020, for female patients aged 18 to 85 years. Descriptive statistics characterized patterns of breast cancer screening before and during the COVID-19 pandemic. Logistic regression analyses examined whether receipt of breast MRI differed over time and demographic and clinical factors associated with receipt of breast MRI in 2020. Results: Data included 47 956 mammography visits in 32 778 patients and 407 screening breast MRI visits in 340 patients. After an initial decrease following the declaration of the COVID-19 pandemic, both screening mammograms and screening breast MRI demonstrated early recovery. Although the mammography receipt remained sustained, the receipt of screening breast MRI decreased in late 2020. Odds of having a breast MRI did not differ between 2018 and 2019 (OR = 1.07; 95% CI = 0.92%-1.25%; P = 0.384) but were significantly lower in 2020 versus 2019 (OR = 0.76; 95% CI = 0.61%-0.94%; P = 0.011). No demographic or clinical factors were associated with receipt of breast MRI during the COVID-19 pandemic (all P-values ≥0.225). Conclusion: Breast cancer screening decreased following the declaration of the COVID-19 pandemic. Although both procedures demonstrated early recovery, the rebound in screening breast MRI was not sustained. Interventions promoting return to screening breast MRI may be needed for high-risk women.

Can Lead-Free Double Halide Perovskites Serve as Proper Photovoltaic Absorber?

The emerging Pb-free double perovskites (DPs) are acknowledged as the most potential nontoxic alternatives to lead halide perovskites for thin-film photovoltaics, yet their photophysical properties significantly lag behind expectations. To tackle this issue, it is imperative to conduct a systematic investigation of the structure and optoelectronic properties and to sift through vast chemical space to extract new types of Pb-free DPs with exceptional optoelectronic characteristics and thermal stability. Through high-throughput first-principal calculations, we demonstrate that apart from a select few Pb-free DPs (e.g., Cs2InSbCl6 and Cs2TlBiBr6), other categories, even with suitable direct electronic bandgaps, exhibit inferior optical absorption due to the inversion symmetry-induced parity-forbidden transitions. The mismatch between the electronic and optical bandgap, thence, casts doubt on the reliability of the electronic bandgap as a criterion for Pb-free DPs in various optoelectronics. The assessed limited thermostability under operational conditions, however, hinders any Pb-free DPs from effectively serving as photovoltaic absorbers. Alongside the compositional engineering discussed above, the prospect of manipulating local-site symmetry and disrupting the parity forbidden transitions in stabilized Pb-free DPs through materials engineering should be recognized as a pivotal and rational avenue toward achieving high performance.

Comparison of the efficacy and safety of leflunomide versus mycophenolate mofetil in treating IgG4-related disease: a retrospective cohort study.

OBJECTIVE: Combination therapy of glucocorticoids (GCs) plus leflunomide (LEF) and GCs plus mycophenolate mofetil (MMF) was reported to have good efficacy and safety in the management of IgG4-RD. However, studies comparing the efficacy and safety of these two combination therapies were unavailable. Herein, this study aimed to compare the efficacy and safety of GCs plus LEF and GCs plus MMF in treating IgG4-RD. METHODS: This study included 130 newly diagnosed IgG4-RD patients who received the therapy of GCs plus LEF (group I) and GCs plus MMF (group II). Clinical data at baseline and after treatment, treatment response, relapse rate, and adverse effects were recorded and analyzed. RESULTS: Patients in both groups responded well to the treatment in the 1st-month follow-up, and 100% of patients achieved treatment response. However, at the 6th and 12th-month follow-up, the total response rate of group II was higher than that in group I (75.6 vs. 53.7%, p = 0.038 and 85.4% vs. 61.0%, p = 0.013, respectively). In addition, the duration of disease remission in group II was longer than that in group I (9 (6-9) vs. 6 (6-6) months, p = 0.014). Moreover, more patients in group I had adverse effects compared with group II (36.6 vs. 7.3%, p < 0.01); and the most common adverse events of LEF were rash (12.2%) and elevation of liver enzymes (9.8%). CONCLUSION: The combination therapy of GCs plus low-dose MMF had better efficacy and safety in the management of IgG4-RD compared with the therapy of GCs plus LEF.

Effects of Ruanmailing in Blocking Early Stages of Atherosclerosis by TNF-α Regulation via Kir2.1.

Objective: Ruanmailing oral solution consists of 16 herbs, has anti-lipid peroxidation activity, protects vascular endothelial cells, and improves vascular elasticity. It is an effective drug for the treatment of atherosclerosis (AS). The objective of this study was to investigate the mechanism underlying the antiatherosclerotic effects of Ruanmailing oral solution. Methods: Macrophages were isolated, cultured, and divided into the macrophage control; macrophage foam cell; and low-, medium-, and high-concentration Ruanmailing groups. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay, and the expression levels of inward-rectifier potassium ion channel 2.1 (Kir2.1) and tumor necrosis factor (TNF)-α were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. Results: CCK-8 assay results showed that the tested concentrations of Ruanmailing solution did not affect macrophage proliferation. RT-PCR and Western blot assays indicated that TNF-α expression increased significantly with the formation of macrophage foam cells (P < 0.05). In addition, significant decreases in Kir2.1 and TNF-α expression were observed following treatment with various concentrations of Ruanmailing (P < 0.05). Conclusion: Based on the results, Ruanmailing affects macrophage foam cell formation by regulating Kir2.1 expression, which in turn reduces TNF-α expression and exerts antiatherosclerotic effects. These findings provide a scientific basis for the use of traditional Chinese medicine for AS treatment.