Perchlorate is an environmental pollutant that has been a focus of attention in recent years. It has been detected in many environmental water bodies and drinking water in China, with a high level of presence in some areas of the Yangtze River Basin. The human body may ingest perchlorate through exposure pathways such as drinking water and food, and its main health effect is to affect the thyroid's absorption of iodine. The "Standards for Drinking Water Quality" (GB5749-2022) includes perchlorate as an expanded indicator of water quality, with a limit value of 0.07 mg/L. This article analyzes the technical content related to the determination of hygiene standard limits for perchlorate in drinking water, including the environmental presence level and exposure status of perchlorate, main health effects, derivation of safety reference values, and determination of hygiene standard limits.
Humans ; Water Quality ; Drinking Water ; Perchlorates/analysis* ; China ; Water Pollutants, Chemical/analysis*

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.
Humans ; Multiple Myeloma/drug therapy* ; Bortezomib/therapeutic use* ; Hypercalcemia ; Prognosis ; Chromosome Aberrations ; Kidney/physiology* ; Renal Insufficiency, Chronic ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols

Water eutrophication poses great threats to protection of water environment. Microbial remediation of water eutrophication has shown high efficiency, low consumption and no secondary pollution, thus becoming an important approach for ecological remediation. In recent years, researches on denitrifying phosphate accumulating organisms and their application in wastewater treatment processes have received increasing attention. Different from the traditional nitrogen and phosphorus removal process conducted by denitrifying bacteria and phosphate accumulating organisms, the denitrifying phosphate accumulating organisms can simultaneously remove nitrogen and phosphorus under alternated anaerobic and anoxic/aerobic conditions. It is worth noting that microorganisms capable of simultaneously removing nitrogen and phosphorus absolutely under aerobic conditions have been reported in recent years, but the mechanisms remain unclear. This review summarizes the species and characteristics of denitrifying phosphate accumulating organisms and the microorganisms capable of performing simultaneous nitrification-denitrification and phosphorous removal. Moreover, this review analyzes the relationship between nitrogen removal and phosphorus removal and the underlying mechanisms, discusses the challenges of denitrifying phosphorus removal, and prospects future research directions, with the aim to facilitate process improvement of denitrifying phosphate accumulating organisms.
Phosphorus ; Phosphates ; Wastewater ; Denitrification ; Waste Disposal, Fluid ; Nitrogen ; Bioreactors/microbiology* ; Nitrification ; Sewage

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*

BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Adult ; Humans ; United States/epidemiology* ; Nitrates/adverse effects* ; Nutrition Surveys ; Thiocyanates/urine* ; Perchlorates/urine* ; Creatinine ; Environmental Exposure ; Renal Insufficiency, Chronic/epidemiology* ; Logistic Models

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
Mice ; Animals ; Durapatite/metabolism* ; Dental Enamel/metabolism* ; Ameloblasts/metabolism* ; Amelogenesis ; Stem Cells ; Organoids

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.
Humans ; Antipyretics/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Influenza, Human/drug therapy* ; Nucleic Acids/therapeutic use* ; Oseltamivir/therapeutic use* ; Phosphates/therapeutic use* ; Treatment Outcome ; Double-Blind Method