Investigation of laccase activity in cholinium-based ionic liquids using experimental and molecular dynamics techniques.

Laccases hold great potential for biotechnological applications, particularly in environmental pollutant remediation. Laccase activity is governed by the solvent environment, and ionic liquids (ILs) emerge as a versatile solvent for activation or stabilization of enzymes. Herein, effects of cholinium-based ILs formulated with carboxylic acids, inorganic acid, and amino acids as anionic species, on the catalytic activity of laccase from Trametes versicolor were investigated by experimental and computational approaches. Experimental results showed that laccase activity was enhanced by 21.39 % in 0.5 M cholinium dihydrogen citrate ([Cho][DHC]), in relation to the laccase activity in phosphate buffer medium. However, cholinium aminoate ILs negatively affected laccase activity, as evidenced by the partial deactivation of laccase in both cholinium glycinate and cholinium phenylalaninate, at concentrations of 0.1 M and 0.5 M, respectively. Molecular dynamics studies revealed that the enhancement of laccase activity in [Cho][DHC] might be attributed to the highly stabilized and compact structure of laccase, facilitating a better internal electron transfer during the laccase-substrate interactions. Enhanced catalytic performance of laccase in [Cho][DHC] was postulated to be driven by the high accumulation level of dihydrogen citrate anions around laccase's surface. [Cho][DHC] holds great promise as a cosolvent in laccase-catalyzed biochemical reactions.

Cardiac power output ratio: Novel survival predictor after percutaneous ventricular assist device in cardiogenic shock.

AIMS: Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24 h divided by early CPO (30 min to 2 h), in CS patients after PVAD. METHODS AND RESULTS: Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90 days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24 h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients. CONCLUSION: In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90 days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD.

Efficacy of soothing cream gel in the range of motion and chronic pain at the shoulder and elbow: protocol of a double-blinded, randomised, placebo-controlled trial.

INTRODUCTION: Upper limb problems have a significant impact on the global population leading to pain and restricted joint mobility, ultimately impacting their quality of life. Traditional treatments, such as non-steroidal anti-inflammatory drugs and corticosteroids, often come with undesirable side effects, prompting patients to seek alternative therapies. In this trial, we hypothesise that soothing cream gel (SCG) will improve range of motion and chronic pain in the shoulder and elbow. The objective of this trial is to evaluate the efficacy of SCG in improving the range of motion and chronic pain in the shoulder and elbow. METHODS AND ANALYSIS: A double-blinded, randomised, placebo-controlled trial is conducted to compare the effects of SCG and placebo gel. SCG contains Vitis vinifera essence, Melaleuca viridiflora essential oil, etc, and is manufactured according to Good Manufacturing Practice standards. The placebo gel will be processed with similar appearance, texture and scent but will lack active ingredients. 70 participants with upper limb problems will be recruited from four study sites, including clinical centres and a sport department at the Chinese University of Hong Kong (CUHK). Participants will be randomly assigned to either treatment group or placebo group for 2 weeks. Primary outcome will be the range of motion in the upper limb, assessed by a goniometer, to measure active flexion and abduction for the shoulder, and active flexion and extension for the elbow. The primary efficacy analyses will be based on the full analysis set following the intention-to-treat principle. ETHICS AND DISSEMINATION: The trial has obtained approval from the joint CUHK-New Territories East Cluster (CRE-2023.142), and the patient enrolment commenced in July 2023. Written informed consent will be obtained from all participants prior to participation. Study results will be disseminated through publication in peer-reviewed journals and presentations at conference. TRIAL REGISTRATION NUMBER: NCT05799391.

Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial.

BACKGROUND: Diabetes leads to chronic kidney disease (CKD) and kidney failure, requiring dialysis or transplantation. Astragalus, a common herbal medicine and US pharmacopeia-registered food ingredient, is shown kidney protective by retrospective and preclinical data but with limited long-term prospective clinical evidence. This trial aimed to assess the effectiveness of astragalus on kidney function decline in macroalbuminuric diabetic CKD patients. METHODS: This randomized, assessor-blind, standard care-controlled, multi-center clinical trial randomly assigned 118 patients with estimated glomerular filtration rate (eGFR) of 30-90 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) of 300-5000 mg/g from 7 public outpatient clinics and the community in Hong Kong between July 2018 and April 2022 to add-on oral astragalus granules (15 gs of raw herbs daily equivalent) or to continue standard care alone as control for 48 weeks. Primary outcomes were the slope of change of eGFR (used for sample size calculation) and UACR of the intention-to-treat population. Secondary outcomes included endpoint blood pressures, biochemistry, biomarkers, concomitant drug change and adverse events. (ClinicalTrials.gov: NCT03535935) RESULTS: During the 48-week period, the estimated difference in the slope of eGFR decline was 4.6 ml/min/1.73m2 per year (95 %CI: 1.5 to 7.6, p = 0.003) slower with astragalus. For UACR, the estimated inter-group proportional difference in the slope of change was insignificant (1.14, 95 %CI: 0.85 to 1.52, p = 0.392). 117 adverse events from 31 astragalus-treated patients and 41 standard care-controlled patients were documented. The 48-week endpoint systolic blood pressure was 7.9 mmHg lower (95 %CI: -12.9 to -2.8, p = 0.003) in the astragalus-treated patients. 113 (96 %) and 107 (91 %) patients had post-randomization and endpoint primary outcome measures, respectively. CONCLUSION: In patients with type 2 diabetes, stage 2 to 3 CKD and macroalbuminuria, add-on astragalus for 48 weeks further stabilized kidney function on top of standard care.

Immunogenicity and Safety of the Three-Dose COVID-19 Vaccine Regimen in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis.

Background: A three-dose regimen is the current standard for COVID-19 vaccination, but systematic data on immunogenicity and safety in chronic kidney disease patients remains limited. Objectives: We conducted a meta-analysis on the immunogenicity and safety of three-dose COVID-19 vaccination in patients on renal replacement therapy (RRT). Methods: Systematic literature search in four electronic databases yielded twenty eligible studies (2,117 patients, 94% of whom received mRNA vaccines) for meta-analysis. Results: The overall seropositivity rate of anti-SARS-CoV-2 was 74.2% (95% CI: 65.0-83.4%) after three-dose COVID-19 vaccination. The seropositivity rate of anti-SARS-CoV-2 in kidney transplant recipients (KTRs) was 64.6% (95% CI: 58.7-70.5%), and 43.5% (95% CI: 38.5-48.6%) of non-responders after second dose became seropositive after third dose. The seropositivity rate of anti-SARS-CoV-2 was 92.9% (95% CI: 89.5-96.2%) in dialysis patients, and 64.6% (95% CI: 46.8-82.3%) of non-responders after second dose became seropositive after third dose. In KTRs, each year increase in transplant vintage was associated with 35.6% increase in anti-SARS-CoV-2 seropositivity (95% CI: 15.9-55.4%, p = 0.01). There were no serious adverse events attributed to vaccination in KTRs, and the commonest local and systemic adverse events were injection site pain and fatigue, respectively. Conclusion: Three-dose COVID-19 vaccination regimen in patients on RRT is associated with reduced immunogenicity, especially in KTRs. There are no adverse events associated with third-dose COVID-19 vaccine in KTRs.

Retrograde closure of post-infarct ventricular septal rupture to avoid moderator band entanglement.

A 63-year-old man presented with delayed inferior ST-elevation myocardial infarction complicated with ventricular septal rupture (VSR). He developed cardiogenic shock and respiratory failure requiring intubation and Impella (Abiomed) support.

Long Non-coding RNA Neat1, NLRP3 Inflammasome, and Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear. METHODS: We explored the role of lncRNA Neat1 in (1) a cross-sectional and a longitudinal cohort of AKI in human; (2) three murine models of septic and aseptic AKI and (3) cultured C1.1 mouse kidney tubular cells. RESULTS: In human, hospitalized patients with AKI (n=66) demonstrated significantly increased lncRNA Neat1 levels in urinary sediment cells and buffy coat versus control participants (n=152) from a primary care clinic; and among 6 kidney transplant recipients, Neat1 levels were highest immediately after transplant surgery followed by a prompt decline to normal levels in parallel with recovery of kidney function. In mice with AKI induced by sepsis (via LPS injection or cecal ligation and puncture) and renal ischemia-reperfusion, kidney tubular Neat1 was increased versus sham-operated mice. Knockdown of Neat1 in the kidney using short hairpin RNA preserved kidney function, suppressed overexpression of the AKI biomarker NGAL, leukocyte infiltration and both intrarenal and systemic inflammatory cytokines IL-6, CCL-2 and IL-1ß. In LPS-treated C1.1 cells, Neat1 was overexpressed via TLR4/NF-κB signaling, and translocated from the cell nucleus into the cytoplasm where it promoted activation of NLRP3 inflammasomes via binding with the scaffold protein Rack1. Silencing Neat1 ameliorated LPS-induced cell inflammation, whereas its overexpression upregulated IL-6 and CCL-2 expression even without LPS stimulation. CONCLUSIONS: Our findings demonstrate a pathogenic role of Neat1 induction in human and mice during AKI with alleviation of kidney injury in 3 experimental models of septic and aseptic AKI after knockdown of Neat1. LPS/TLR4-induced Neat1 overexpression in tubular epithelial cells increases the inflammatory response by binding with the scaffold protein, Rack1, to activate NLRP3 inflammasomes.

Modified Qing-Zao-Jiu-Fei decoction attenuated pulmonary fibrosis induced by bleomycin in rats via modulating Nrf2/NF-κB and MAPKs pathways.

BACKGROUND: Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms. METHODS: BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days. RESULTS: MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats. CONCLUSIONS: MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways.

Enhanced activity of Candida antarctica lipase B in cholinium aminoate ionic liquids: a combined experimental and computational analysis.

As a class of ionic liquids with higher biocompatibility, cholinium aminoates ([Cho][AA]) hold potential as solvation media for enzymatic bioprocessing. Herein, solvation effect of [Cho][AA] on structural stability and enzymatic activity of Candida antarctica lipase B (CALB) was evaluated using experimental and computational approaches. Influence of [Cho][AA] on CALB stability was investigated using amino acid anions ([AA]-) with varying hydrophobicity levels. Choline phenylalaninate ([Cho][Phe]) resulted in 109.1% and 110.4% of relative CALB activity to buffer medium at 25 °C and 50 °C, respectively. Simulation results revealed the improvement of CALB's enzymatic activities by [AA]- with a strong hydrophobic character. Shielding of CALB from water molecules by [AA]- was observed. The level of CALB activity was governed by accumulation level of [AA]- at CALB's first hydration layer. The stronger interaction between His224 and Asp187 was postulated to be driven by [Cho][AA], resulting in the activity enhancement of CALB. The slight improvement of CALB activity in 0.05 M [Cho][Phe] at 50 °C could be due to the larger size of entrance to the catalytic site and the stronger interaction between the catalytic residues. The promising effect of [Cho][Phe] on CALB activation may stimulate research efforts in designing a 'fully green' bioreaction for various industrial applications.Communicated by Ramaswamy H. Sarma.

Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease.

Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25-75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300-5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72-0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71-0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60-0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.

Ruptured chordae during percutaneous mitral commissurotomy: immediate recognition by intracardiac echocardiography.

Traditionally, percutaneous mitral commissurotomy (PMC) is performed under fluoroscopy only. In difficult cases, general anesthesia with transesophageal echocardiography (TEE) guidance is needed. Intracardiac echocardiography (ICE) enables operators to perform PMC under local anesthesia while providing intra-procedural imaging guidance, as in TEE. Hereby, we describe a case of PMC guided by ICE to allow early detection of complications.

Corrigendum: A Chinese medicine formula (Bushen Huoxue Tongluo) for the treatment of chronic subjective tinnitus: a study protocol for a pilot, assessor-blinded, randomized clinical trial.

[This corrects the article DOI: 10.3389/fphar.2022.844730.].

Impacts of sulfur fumigation on the chemistry and immunomodulatory activity of polysaccharides in ginseng.

Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.

Electroacupuncture with or without combined warm needling for tinnitus: Study protocol for a randomized, waitlist-controlled trial.

BACKGROUND: Tinnitus is a common auditory condition that can lead to serious problems. Clinically, acupuncture and moxibustion have been commonly applied to treat tinnitus in China, with potential therapeutic effects but with limitations in study methodology and high-quality evidence. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of either electroacupuncture alone or combined with warm needling for reducing tinnitus loudness and improving quality of life. METHODS: This study is a prospective, multicenter, assessor-blind, 3-arm, parallel-group, randomized, waitlist-controlled trial. In total, 90 patients will be randomly assigned to the electroacupuncture, electroacupuncture and warm needing, or waitlist control group in a 1:1:1 ratio. Patients in the 2 treatment groups will be treated twice a week for a total of 5 weeks. Patients in the control group will not receive treatment during the study period and will be informed that they can receive it for free after a 10-week waiting period. The duration of intervention for this study will be 5 weeks, followed by another 5 weeks for the posttreatment assessment. The primary outcome is the change in the visual analog scale score for tinnitus loudness from baseline until the end of treatment. The secondary outcome is the tinnitus discomfort assessment measured using the Tinnitus Handicap Inventory. Outcome parameters will be assessed at baseline and at weeks 5 and 10. Any adverse events will be observed and recorded for safety assessment. Linear mixed models for repeated measures will be applied in the analysis. DISCUSSION: Acupuncture and moxibustion could be potentially effective treatment alternatives for tinnitus. The study results will provide evidence to determine the efficacy and safety of electroacupuncture with or without warm needling for tinnitus.

Therapeutic effect of Duhuo Jisheng Decoction add-on Tui-na manipulation on osteoarthritis of knee: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint condition that causes disability and pain in the elderly population. The prevalence of KOA among persons aged 63 or above is approximately 30%. Previous studies have reported the positive effects of Tui-na treatment and the Chinese herbal formula Du-Huo-Ji-Sheng Decoction (DHJSD) for KOA treatment. The current study aims to evaluate the add-on therapeutic effect of oral administration of DHJSD on KOA in addition to Tui-na. METHODS: We conducted a prospective, randomized, controlled clinical trial. Seventy study subjects with KOA were randomly assigned to the treatment and control groups in a 1:1 ratio. Both two groups received eight sessions of Tui-na manipulation for 4 weeks. The DHJSD was only administered to the study subjects in the treatment group. The primary outcome measure was rated using the WOMAC at the end of treatment (4 weeks). Secondary outcomes were assessed using EQ-5D-5L, a health-related quality of life with 5-level EQ-5D version at end of treatment (week 4) and follow-up (week 8). RESULTS: No statistically significant difference was found between two groups on WOMAC scores at the end of treatment. The mean WOMAC Pain subscale score was significantly lower in the treatment group than control group at week 8 follow up (mean difference, MD - 1.8, 95% CI - 3.5 to - 0.02, P = 0.048). The mean WOMAC Stiffness subscale score was significantly lower in the treatment group than in the control group at week 2 (MD 0.74, 95% CI 0.05 to 1.42, P = 0.035) and week 8 follow up (MD 0.95, 95% CI 0.26 to 1.65, P = 0.008). The mean EQ-5D index value was significantly improved in the treatment group than in the control group at week 2 (MD 0.17, 95% CI 0.02 to 0.31, P = 0.022). The analysis of WOMAC scores and EQ-5D-5L in both groups showed statistically significant improvement with time. No significant adverse effect was found during the trial. CONCLUSION: DHJSD may have an add-on effect in addition to Tui-na manipulation relieving pain and improving stiffness as well as quality of life (QOL) in patients with KOA. The combined treatment was generally safe and well tolerated. Trial registration The study was registered at the ClinicalTrials.gov (website: https://clinicaltrials.gov/ct2/show/NCT04492670 , registry number: NCT04492670), registered on 30 July 2020.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

Impact of Sulfur Fumigation on the Chemistry of Dioscoreae Rhizoma (Chinese Yam).

Dioscoreae Rhizoma (Chinese yam; derived from the rhizome of Dioscorea opposita Thunb.) (DR), commonly consumed as a food or supplement, is often sulfur-fumigated during post-harvest handling, but it remains largely unknown if and how sulfur fumigation impacts the chemistry of DR. In this study, we report the impact of sulfur fumigation on the chemical profile of DR and then the molecular and cellular mechanisms potentially involved in the chemical variations induced by sulfur fumigation. The results show that sulfur fumigation significantly and specifically changed the small metabolites (molecular weight lower than 1000 Da) and polysaccharides of DR at both qualitative and quantitative levels. Multifaceted molecular and cellular mechanisms involving chemical transformations (e.g., acidic hydrolysis, sulfonation, and esterification) and histological damage were found to be responsible for the chemical variations in sulfur-fumigated DR (S-DR). The research outcomes provide a chemical basis for further comprehensive and in-depth safety and functional evaluations of sulfur-fumigated DR.