Association between sarcopenia and new-onset chronic kidney disease among middle-aged and elder adults: findings from the China Health and Retirement Longitudinal Study.

BACKGROUND: Sarcopenia is a senile syndrome of age-related muscle loss. It is thought to affect the development of chronic kidney disease and has a serious impact on the quality of life of the elder adults. Little is known about the association between sarcopenia and new-onset chronic kidney disease in middle-aged and elder adults. Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a longitudinal analysis to investigate the association between sarcopenia status and new-onset chronic kidney disease in middle-aged and elder adults in China. METHODS: The study population consisted of 3676 participants aged 45 or older selected from 2011 CHARLS database who had no history of chronic kidney disease at the baseline and completed the follow-up in 2015. A multivariate cox regression model was employed to examine the association between sarcopenia and the incidence of new-onset chronic kidney disease. RESULTS: Followed up for 4 years, a total of 873 (22.5%) new cases of chronic kidney disease occurred. Among them, participants diagnosed with sarcopenia (HR1.45; 95% CI 1.15-1.83) were more likely to develop new-onset chronic kidney disease than those without sarcopenia. Similarly, patients with sarcopenia were more likely to develop new-onset chronic kidney disease than those with possible sarcopenia (HR 1.27; 95%CI 1.00-1.60). Subgroup analysis revealed that elder adults aged between 60 and 75 years old (HR 1.666; 95%CI 1.20-22.28), with hypertension (HR 1.57; 95%CI 1.02-2.40), people with sarcopenia had a significantly higher risk of developing new-onset chronic kidney disease than those without sarcopenia (all P < 0.05). CONCLUSION: Middle-aged and elder adults diagnosed with sarcopenia have a higher risk of developing new-onset chronic kidney disease.

Pull-through technique through antegrade radial artery puncture without sheath insertion in balloon-assisted radiocephalic arteriovenous fistulas maturation.

PURPOSE: The aim of this study was to investigate the effectiveness and safety of the pull-through technique through antegrade radial artery puncture without sheath insertion in balloon-assisted radiocephalic AVF maturation. METHODS: We retrospective studied a total of 62 patients with immature radiocephalic AVF, who received balloon-assisted maturation in our hospital. 15 patients received pull-through technique through radial artery without sheath insertion and 47 patients received treatment through a regular venous approach. RESULTS: The success rate of pull-through technique group and control group was 86.7% (13 out of 15), 89.1% (41 out of 46) respectively. There was no significant difference between two groups (P > 0.05). In our study, there were 2 patients in the pull-through technique group and 3 patients in the control group, which had hematoma in the vein puncture site (P = 0.59). There were also no differences in the primary patency rate between two groups at 6 months and 12 months (76.9% vs 70.7%, 38.4% vs 41.5%, respectively, P > 0.05). CONCLUSION: The pull-through technique through antegrade radial artery without sheath insertion in promoting radiocephalic AVF maturation is effective and safe.

GLIM criteria for definition of malnutrition in peritoneal dialysis: a new aspect of nutritional assessment.

Background: The aim of our study was to evaluate the effectiveness of Global Leadership Initiative on Malnutrition (GLIM) criteria in assessing malnutrition within the peritoneal dialysis (PD) population.Methods: We conducted a retrospective analysis involving 1057 PD patients across multiple institutions, characterized by an age of 56.1 ± 14.4 years, 464 (43.9%) female, and a median follow-up of 45 (25, 68) months. Malnutrition was diagnosed according to GLIM criteria. The endpoint event was overall mortality. The survival rate and hazard ratio (HR) of death between malnutrition and well-nourished were analyzed in all patients and various subgroups. Receiver operator characteristic curve and integrated discrimination improvement (IDI) were used to distinguish the efficacy of the nutritional tools prediction model.Results: According to the GLIM criteria, the prevalence of malnutrition among the study population was 34.9%. The adjusted HR of overall mortality was 2.91 (2.39 - 3.54, p < 0.001) for malnutrition versus well-nourished. In sensitivity analyses, the HR remained robust except the cardiovascular disease subgroup. The area under the curve of GLIM predicting 5-year mortality was 0.65 (0.62-0.68, p < 0.001). As a complex model for forecast the long-term mortality, the performance of adjusted factors combined with GLIM was poorer than combined malnutrition inflammation score (MIS) (IDI >0, p < 0.001), but fitter than combined geriatric nutritional risk index (GNRI) (IDI <0, p < 0.001).Conclusions: The GLIM criteria provide a viable tool for nutritional assessment in patients with PD, and malnutrition defined according to the GLIM can predict prognosis with an acceptable performance.

Discovery of novel cGAS inhibitors based on natural flavonoids.

Cyclic GMP-AMP synthase (cGAS) plays an important role in the inflammatory response. It has been reported that aberrant activation of cGAS is associated with a variety of immune-mediated inflammatory disorders. The development of small molecule inhibitors of cGAS has been considered as a promising therapeutic strategy for the diseases. Flavonoids, a typical class of natural products, are known for their anti-inflammatory activities. Although cGAS is closely associated with inflammation, the potential effects of natural flavonoid compounds on cGAS have been rarely studied. Therefore, we screened an in-house natural flavonoid library by pyrophosphatase (PPiase) coupling assay and identified novel cGAS inhibitors baicalein and baicalin. Subsequently, crystal structures of the two natural flavonoids in complex with human cGAS were determined, which provide mechanistic insight into the anti-inflammatory activities of baicalein and baicalin at the molecular level. After that, a virtual screening based on the crystal structures of baicalein and baicalin in complex with human cGAS was performed. As a result, compound C20 was identified to inhibit both human and mouse cGAS with IC50 values of 2.28 and 1.44 µM, respectively, and its detailed interactions with human cGAS were further revealed by the X-ray crystal structure determination. These results demonstrate the potential of natural products used as hits in drug discovery and provide valuable hints for further development of cGAS inhibitors.

Visit-to-visit HbA1c variability is associated with poor prognosis in peritoneal dialysis patients with type 2 diabetes mellitus.

BACKGROUND: The prognosis of diabetic peritoneal dialysis patients is poor. HbA1c serves as a crucial indicator for monitoring blood glucose control in patients with diabetes. Nevertheless, the relationship between visit-to-visit HbA1c variability and prognosis in peritoneal dialysis with diabetes remains unclear. METHODS: All participants were categorized into 3 groups based on the HbA1c variability score (HVS), which is the frequency of 0.5% (5.5 mmol/mol) alter in visit-to-visit HbA1c values. Then, the hazard ratio to HVS with all-cause mortality was analyzed using the Cox hazard model, followed by the Fine-Gray competing risk model for major adverse cardiovascular events. Subgroup and sensitivity analysis were conducted to ascertain the robustness of the findings. RESULTS: Eight hundred twenty patients with type 2 diabetes were finally enrolled in this study from 2,855 participants with a mean age of 56.9 ± 14.6 years and a median follow-up time of 44 months [IQR: 27-70], death occurred in 496 (60.2%) individuals. Compared with the lowest category (HVS < 1/3) after being adjusted by potential confounding factors, the hazard ratio for all-cause mortality was 4.59 (3.74-5.64) and the sub-distribution hazard ratio for major adverse cardiovascular events was 1.91 (1.46-2.51) of the highest category (HVS ≥ 2/3). Subgroup interaction and sensitivity analysis, including the adjustment for variables such as time-weighted average HbA1c, HbA1c measurement times and expansion, confirmed the reliability of the results. CONCLUSION: The HVS is related to the risk of poor prognosis in peritoneal dialysis with type 2 diabetes mellitus, independently of clinical multiple variables, and is a novel indicator with clinical guidance.

Circ_0005925 Promotes Granulosa Cell Growth by Targeting MiR-324-3p to Upregulate MAP2K6 in Polycystic Ovary Syndrome.

Circular RNA has been reported to be involved in the development of polycystic ovary syndrome (PCOS), but the role of circ_0005925 in the progression of PCOS is unclear. The expression levels of circ_0005925, microRNA (miR)-324-3p, and MAPK kinase 6 (MAP2K6) were examined by quantitative real-time PCR. Cell proliferation and apoptosis were determined using cell counting kit 8 assay, EdU assay, colony formation assay, and flow cytometry. Western blot analysis was used to detect the protein expression of apoptosis markers and MAP2K6. RNA interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0005925 was upregulated in GCs from PCOS patients, as well as in KGN and SVOG cells. Circ_0005925 knockdown repressed GCs proliferation and promoted apoptosis. MiR-324-3p was downregulated in PCOS patients, and it was sponged by circ_0005925. The regulation of circ_0005925 knockdown on GCs growth was abolished by miR-324-3p inhibitor. MAP2K6 was targeted by miR-324-3p, and its expression was positively regulated by circ_0005925. MiR-324-3p inhibited GCs proliferation and increased apoptosis by targeting MAP2K6. Collectively, our findings suggested that circ_0005925 promoted GCs growth through miR-324-3p/MAP2K6, which provided a promising therapeutic target for PCOS.

Pan-immune-inflammation value is associated with poor prognosis in patients undergoing peritoneal dialysis.

BACKGROUND: Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a novel comprehensive biomarker, the pan-immune-inflammation value (PIV), and the prognosis of patients undergoing PD. METHODS: We retrospectively analyzed data from a multicenter, large-sample PD database. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count. The prognostic endpoints in this study were all-cause death all-cause, cardiovascular disease (CVD) and infection-related death. The Kaplan-Meier method, a Cox proportional hazards regression, Fine-Gray competing risk model, smooth curve, and subgroup analysis were used to analyze the independent relationship between PIV and the prognosis of patients undergoing PD. RESULTS: A total of 2796 cases of PD were included, and the study population was divided into Tertiles 1, 2, and 3, according to the tertiles of baseline PIVs. After adjusting for multiple model factors, patients in the Tertile 3 group had a significantly higher risk of all-cause death, CVD death and infection-related death compared with patients with PIV in the Tertile 1 group. Interaction tests showed no positive correlations for subgroup parameters. Regarding all-cause death, compared with the lowest tertile, the multivariable-adjusted hazard ratios (95% confidence intervals) of the highest and middle tertiles were 1.55 (1.25-1.94) and 1.77 (1.43-2.19), respectively; PIV (log2 processing) was associated with 17% excess of mortality in the continuous model. CONCLUSIONS: A high PIV at baseline was significantly associated with an increased risk of deaths due to all-causes, CVD and infection in patients undergoing PD.

Intermolecular Carbophosphination of Alkynes with Phosphole Oxides via Ni-Al Bimetal-Catalyzed C-P Bond Activation.

Intermolecular carbophosphination reaction of alkynes or alkenes with unreactive C-P bonds remains an elusive challenge. Herein, we used a Ni-Al bimetallic catalyst to realize an intermolecular carbophosphination reaction of alkynes with 5-membered phosphole oxides, providing a series of 7-membered phosphepines in up to 94 % yield.

Hypomagnesemia Is a Risk Factor for Cardiovascular Disease- and Noncardiovascular Disease-Related Mortality in Peritoneal Dialysis Patients.

PURPOSE: Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients. METHOD: In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7-1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes. RESULTS: Cox multiple regression analysis results (reference comparison of 0.7-1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222-2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196-2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114-2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011-2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131-3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480-0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05). CONCLUSIONS: Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes.

Enantioselective Nickel-Catalyzed C(sp3 )-H Activation of Formamides.

Enantioselective Ni-catalyzed C(sp3 )-H bond activation remains an elusive challenge. Herein, we used phosphine oxide-ligated Ni-Al bimetallic catalyst to realize enantioselective Ni-catalyzed aliphatic C(sp3 )-H activation of formamides, providing a series of chiral N-containing heterocycles in 40-95 % yield and 70-95 % ee.

Carbamoyl Fluoride-Enabled Enantioselective Ni-Catalyzed Carbocarbamoylation of Unactivated Alkenes.

A carbamoyl fluoride-enabled enantioselective Ni-catalyzed carbocarbamoylation of unactivated alkenes was developed, providing a broad range of chiral γ-lactams bearing an all-carbon quaternary center in 45-96% yield and 38-97% ee.

The relationship between neutrophil-to-lymphocyte ratio and the first occurrence of pneumonia in peritoneal dialysis patients.

BACKGROUND: Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients. METHODS: This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan-Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups. RESULTS: Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan-Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04-2.21; p = 0.031). Forest plot showed no interaction was found in subgroups. CONCLUSIONS: The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic.

Neutrophil to Lymphocyte Ratio Predicts Adverse Cardiovascular Outcome in Peritoneal Dialysis Patients Younger than 60 Years Old.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. METHODS: From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74, 2.74 < NLR ≤ 3.96, and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. RESULTS: During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39, 95%CI = 1.01-1.93, P = 0.046) and CVD mortality (HR = 1.81, 95%CI = 1.22-2.69, P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI = 1.26 - 3.23, P = 0.003) and CVD mortality was 2.98 (95%CI = 1.58 - 5.62, P = 0.001) in the younger group (age < 60 years). CONCLUSIONS: NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.

Similar geometric rules govern the distribution of veins and stomata in petals, sepals and leaves.

Investment in leaf veins (supplying xylem water) is balanced by stomatal abundance, such that sufficient water transport is provided for stomata to remain open when soil water is abundant. This coordination is mediated by a common dependence of vein and stomatal densities on cell size. Flowers may not conform to this same developmental pattern if they depend on water supplied by the phloem or have high rates of nonstomatal transpiration. We examined the relationships between veins, stomata and epidermal cells in leaves, sepals and petals of 27 angiosperms to determine whether common spacing rules applied to all tissues. Regression analysis found no evidence for different relationships within organ types. Both vein and stomatal densities were strongly associated with epidermal cell size within organs, but, for a given epidermal cell size, petals had fewer veins and stomata than sepals, which had fewer than leaves. Although our data support the concept of common scaling between veins and stomata in leaves and flowers, the large diversity in petal vein density suggests that, in some species, petal veins may be engaged in additional functions, such as the supply of water for high cuticular transpiration or for phloem delivery of water or carbohydrates.

Leaves, not roots or floral tissue, are the main site of rapid, external pressure-induced ABA biosynthesis in angiosperms.

Rapid biosynthesis of abscisic acid (ABA) in the leaf, triggered by a decrease in cell volume, is essential for a functional stomatal response. However, it is not known whether rapid biosynthesis of ABA is also triggered in other plant tissues. Through the application of external pressure to flower, root, and leaf tissues, we test whether a reduction in cell volume can trigger rapid increases in ABA levels across the plant body in two species, Solanum lycopersicum and Passiflora tarminiana. Our results show that, in contrast to rapid ABA synthesis in the leaf, flower and root tissue did not show a significant, increase in ABA level in response to a drop in cell volume over a short time frame, suggesting that rapid ABA biosynthesis occurs only in leaf, not in flower or root tissues. A gene encoding the key, rate-limiting carotenoid cleavage enzyme (9-cis-epoxycarotenoid dioxygenase, NCED) in the ABA biosynthetic pathway in S. lycopersicum, NCED1, was upregulated to a lesser degree in flowers and roots compared with leaves in response to applied pressure. In both species, floral tissues contained substantially lower levels of the NCED substrate 9'-cis-neoxanthin than leaves, and this ABA precursor could not be detected in roots. Slow and minimal ABA biosynthesis was detected after 2 h in petals, indicating that floral tissue is capable of synthesizing ABA in response to sustained water deficit. Our results indicate that rapid ABA biosynthesis predominantly occurs in the leaves, and not in other tissues.

Are flowers vulnerable to xylem cavitation during drought?

Water stress is known to cause xylem cavitation in the leaves, roots and stems of plants, but little is known about the vulnerability of flowers to xylem damage during drought. This is an important gap in our understanding of how and when plants become damaged by water stress. Here we address fundamental questions about if and when flowers suffer cavitation damage, using a new technique of cavitation imaging to resolve the timing of cavitation in water-stressed flower petals compared with neighbouring leaves. Leaves and flowers from a sample of two herbaceous and two woody eudicots were exposed to a severe water stress while the spatial and temporal propagation of embolism through veins was recorded. Although in most cases water potentials inducing 50% embolism of herbaceous flower veins were more negative than neighbouring leaves, there was no significant difference between the average vulnerability of leaves and petals of herbaceous species. In both woody species, petals were more vulnerable to cavitation than leaves, in one case by more than 3 MPa. Early cavitation and subsequent damage of flowers in the two woody species would thus be expected to precede leaf damage during drought. Similar cavitation thresholds of flowers and leaves in the herb sample suggest that cavitation during water shortage in these species will occur simultaneously among aerial tissues. Species-specific differences in the cavitation thresholds of petals provide a new axis of variation that may explain contrasting flowering ecology among plant species.

[Determination of multi-elements in aquatic feed by microwave plasma-atomic emission spectroscopy].

In the present research, a novel method for quantitative analysis of multi-elements (Cu, Fe, Mn, Zn, K and Na) in aquatic feed was established by using microwave plasma-atomic emission spectroscopy (MP-AES) technology. The sample was pretreated by traditional dry ashing method, and then a series of methodological study experiments, such as the detection limit, the spiked recovery, the precision measurement, the method comparison with AAS and ICP-AES, the standard substance confirmation and so on, were accomplished by MP-AES. The instrument parameters of MP-AES were optimized. In the optimal con- ditions, the linear calibration curve was established for each element, and the linear regression correlation coefficient was more than 0. 999. The limit of detection (LOD) was between 0. 4 and 3. 9 mg . kg-1. The spiked recovery was between 103% and 112%. The relative standard deviation of precision measurement was between 0. 2% and 0. 6%. In the method comparison, the one way ANOVA statistical analysis yielded the p value between 0. 065 and 0. 438, which were greater than 0. 05, there was no statistically significant difference among MP-AES, AAS and ICP-AES. The FAPAS 10102 dairy ration test material and the national standard substances (GBW07602) were prepared for method confirmation in this study, and the measured values were in good agreement with the certified values. Compared with the commercial ICP-AES which typically uses argon as the plasma gas, the MP-AES relies on using nitrogen as the plasma gas, which may provide a more economical alternative to traditional ICP-AES for routine analysis in feed analytical laboratories. The established method was simple, fast, reproducible and accurate, and it was an ideal analysis technique to substitute AAS and ICP-AES for the determination of multi-elements in aquatic feed.

Pleural effusion portends a poor prognosis in patients on continuous ambulatory peritoneal dialysis.

AIMS: Pleural effusion is not an infrequent complication in patients undergoing continuous ambulatory peritoneal dialysis. However, there is not adequate data to evaluate pleural effusion and prognosis in clinical practice. In this study, we validated this potential association by a multicenter cohort. METHODS: We screened 1,162 patients who met the inclusion criteria with PD. According to the existence of pleural effusion on stable dialysis (4-8 weeks after dialysis initiation), the participants were divided into pleural effusion and non-pleural effusion groups. The hazard ratios (HRs) of all-cause and cause-specific death were estimated with adjustment for demographic characteristics and multiple potential clinical confounders. Subgroup analysis and propensity score matching (PSM) were used to further verify the robustness of the correlation between hydrothorax and prognosis. RESULTS: Pleural effusion was found in 8.9% (104/1162) of PD individuals. After adjusting for the confounding factors, patients with pleural effusion had significantly increased HRs for all-cause death was 3.06 (2.36-3.96) and cardiovascular death was 3.78 (2.67-5.35) compared to those without pleural effusion. However, it was not associated with infectious and other causes of death. After PSM, the HR of all-cause mortality was 3.56 (2.28-5.56). The association trends were consistent in the subgroup sensitivity analysis. CONCLUSION: Pleural effusion is not rare in PD, and is significantly associated with overall and cardiovascular mortality, which is independent of underlying diseases and clinically relevant indicators.

Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal disorders and a primary cause of pain and disability among the elderly population. Research on the relationship between metalloproteins (MPs) and OA is limited, and causality remains unclear. Our objective is to utilize Mendelian randomization (MR) to explore the possible causal relationship between MPs and OA. The data on MPs were derived from a Genome-Wide Association Study (GWAS) analysis involving 3301 samples. The GWAS data for OA were obtained from an analysis involving 462,933 European individuals. In this study, a variety of two-sample Mendelian randomization methods (two-sample MR) to evaluate the causal effect of MPs on OA, including inverse variance weighted method (IVW), MR-Egger method, weighted median method (WM), simple mode, weight mode, and Wald ratio. The primary MR analysis using the IVW method reveals a significant negative correlation between Metallothionein-1F (MT-1F), zinc finger protein 134 (ZNF134), calcium/calmodulin-dependent protein kinase type 1D (CAMK1D), and EF-hand calcium-binding domain-containing protein 14 (EFCAB14) with the occurrence of osteoarthritis (OA) (p value < 0.05). However, no causal relationship was observed in the opposite direction between these MPs and OA. Notably, even in combined models accounting for confounding factors, the negative association between these four MPs and OA remained significant. Sensitivity analysis demonstrated no evidence of horizontal pleiotropy or heterogeneity, and leave-one-out analysis confirmed the robustness of the results. In this study, we have established a conspicuous association between four distinct MPs and OA. This discovery augments our understanding of potential avenues for the diagnosis and treatment of this condition. Key Points • The MR method was employed to assess the relationship between MPs and OA. • A total of four types of MPs have demonstrated inhibitory effects on the occurrence of OA.