Clostridioides difficile Infection Risk Following Different Antibiotics: Insights from Multi-source Medical Data.

OBJECTIVE: Antibiotic utilization stands as the strongest modifiable determinant for Clostridioides difficile infection (CDI). However, previous studies have relied on aggregated antibiotic categories, leaving prescribers without detailed comparative risk information for individual antibiotics. Our objective was to comprehensively estimate CDI risks across specific antibiotics. METHODS: We integrated 2 methodologies to access and rank the CDI risk associated with individual antibiotics or classes. Initially, we conducted a network comparison by analyzing data from randomized controlled trials (RCTs). Subsequently, a real-world disproportionality analysis using the Food and Drug Adverse Event Reporting System (FAERS) database complemented and enriched the findings from RCTs. RESULTS: The network comparison, encompassing 61 RCTs with 25,931 patients, revealed that exposure to cefepime (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.20-5.44, P=0.02) and imipenem/cilastatin (OR 3.86, 95%CI 1.61-9.29, P=0.003) exhibited higher frequencies of CDI compared to piperacillin/tazobactam. No statistically significant distinctions emerged among carbapenems, albeit a trend indicating a heightened CDI incidence with imipenem/cilastatin relative to meropenem (OR 3.89, 95%CI 0.94-16.09). In the FAERS disproportionality analysis, nearly all antibiotics displayed associations with CDI, and CDI risk signals often cluster within the majority of antibiotic classes. Among these, lincomycin demonstrated the strongest association (reporting odds ratios 112.17, 95%CI 51.68-243.43). Additionally, oral third-generation cephalosporins tend to exhibit higher CDI risk signals than others. CONCLUSIONS: Our findings unveiled substantial diversity in CDI risk, both within and among antibiotic classes, providing valuable guidance for clinicians in antibiotic prescription decisions and for initiatives aimed at antibiotic stewardship.

Hydroxyl-Amide Alkaloids from Pepper Roots: Potential Sources of Natural Antioxidants and Tyrosinase Inhibitors.

Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.

Deciphering the microbial succession and color formation mechanism of "green-covering and red-heart" Guanyin Tuqu.

"Green-covering and red-heart" Guanyin Tuqu (GRTQ), as a type of special fermentation starter, is characterized by the "green-covering" formed on the surface of Guanyin Tuqu (SQ) and the "red-heart" in the center of Guanyin Tuqu (CQ). However, the mechanisms that promote temporal succession in the GRTQ microbial ecology and the formation of "green-covering and red-heart" characteristics remain unclear. Herein, we correlated the temporal profiles of microbial community succession with the main environmental variables (temperature, moisture, and acidity) and spatial position (center and surface) in GRTQ throughout fermentation. According to the results of high-throughput sequencing and culture-dependent methods, the microbial communities in the CQ and SQ demonstrated functional complementarity. For instance, the bacterial richness index of the CQ was greater than that of SQ, and the fungal richness index of the SQ was greater than that of CQ at the later stage of fermentation. Furthermore, Saccharomycopsis, Saccharomyces, Aspergillus, Monascus, Lactobacillus, Bacillus, Rhodanobacter, and Chitinophaga were identified as the dominant microorganisms in the center, while the surface was represented by Saccharomycopsis, Aspergillus, Monascus, Lactobacillus, Acetobacter, and Weissella. By revealing the physiological characteristics of core microorganisms at different spatial positions of GRTQ, such as Aspergillus clavatus and Monascus purpureus, as well as their interactions with environmental factors, we elucidated the color formation mechanism behind the phenomenon of "green" outside and "red" inside. This study provides fundamental information support for optimizing the production process of GRTQ.

Mendelian randomization analysis reveals a causal relationship between preterm birth and myopia risk.

Background: Preterm birth has been associated with an increased risk of myopia, but the causal relationship between these two factors remains unclear. Traditional epidemiological studies are limited by confounding factors and reverse causality. Mendelian randomization (MR) analysis, utilizing genetic variants as instrumental variables, provides a robust approach to investigate causal relationships. In this study, we aimed to explore the potential causal link between preterm birth and myopia risk using a two-sample MR analysis strategy. Methods: We conducted a Mendelian randomization study to investigate the causal relationship between preterm birth and myopia risk. Genetic variants (single nucleotide polymorphisms, SNPs) were used as instrumental variables, and summary data from genome-wide association studies (GWAS) were utilized. Four regression models, including MR-Egger regression, weighted median regression, inverse variance weighted regression, and Weighted mode regression, were employed to validate the causal relationship. Sensitivity analysis was performed using the leave-one-out method. At the same time, the funnel diagram and MR-Egger test were used to judge the stability of the research results. Results: The MR analysis revealed a significant causal effect of preterm birth on myopia risk. Both the inverse variance weighted regression and weighted median regression models showed a p-value less than 0.05, indicating a robust association. The risk of myopia increased by approximately 30% for everyone standard deviation increase in preterm birth. Sensitivity analysis, funnel plot and MR-Egger test all confirm the stability of the research results. Conclusion: Our findings provide evidence supporting a causal relationship between preterm birth and myopia risk. Preterm infants are at a higher risk of developing myopia, and this association is not likely to be influenced by confounding factors or reverse causality. The SNP loci rs6699397, rs10871582, and rs2570497 should be closely monitored as they may lead to abnormal concentrations of intraocular cytokines, particularly vascular endothelial growth factor, potentially elucidating one of the pathogenic mechanisms contributing to the higher incidence of myopia in preterm infants. However the complex interconnections involved extend beyond these factors alone.

Bodipy-Based highly sensitive hydrogen sulfide fluorescent probe and its fluorescence imaging in cells and zebrafish.

Hydrogen sulfide (H2S) is a crucial endogenous gasotransmitter that plays a role in various physiological and pathological processes. Therefore, accurate and rapid monitoring of H2S in organisms is highly significant for understanding the underlying pathological mechanisms and facilitating early diagnosis of related diseases. In this study, we developed a novel fluorescent probe, B-CHO-NO2, based on a bodipy fluorophore, which exhibits excellent sensitivity and selectivity towards H2S. The design of the probe exploits the nucleophilicity of H2S by introducing a formyl group as the ortho-participating moiety, significantly enhancing the reaction rate with H2S. In cellular and zebrafish models, the probe B-CHO-NO2 successfully achieved fluorescence imaging of endogenous and exogenous H2S. The development of probe B-CHO-NO2 provides a powerful tool for biological studies of H2S and diagnosis of related diseases.

Effects of sorghum varieties on microbial communities and volatile compounds in the fermentation of light-flavor Baijiu.

Light-flavor Baijiu (LFB) fermentation is a representative spontaneous mixed-culture solid-state fermentation process in which sorghum is used as the raw material. Raw materials and microorganisms are crucial to the flavor formation and quality of LFB. However, the microbial and physicochemical dynamics of different sorghum varieties during LFB fermentation, as well as their impact on flavor compounds are still largely unknown. Herein, PacBio single-molecule real-time (SMRT) sequencing and headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) were applied to investigate microbial community succession and volatile flavor formation in glutinous/non-glutinous sorghum-based fermented grains during LFB fermentation. Fermented grains made of glutinous sorghum Liangnuo No. 1 (GLN) had higher bacterial α-diversity and lower fungal α-diversity than those with fermented grains prepared with non-glutinous red sorghum (NRS) (p < 0.05). The dominant microbial species were Saccharomyces cerevisiae, Acetobacter pasteurinus, and Lactobacillus helveticus, the latter two of which were the predominant bacteria observed at the end of fermentation in GLN and NRS, respectively. Moisture content and reducing sugar had a more significant impact on the microorganisms in GLN, while amino acid nitrogen, total free amino acids, and residual starch were the main driving factors driving the microbial community in NRS. The correlation network and discriminant analysis indicated that a relatively high content of 4-vinylguaiacol showed a significant positive association with significant differential microbial species in GLN. These results provided valuable insights for improving the quality of LFB.

Advanced membrane-based high-value metal recovery from wastewater.

Considering the circular economy and environmental protection, sustainable recovery of high-value metals from wastewater has become a prominent concern. Unlike conventional methods featuring extensive chemicals or energy consumption, membrane separation technology plays a crucial role in facilitating the sustainable and efficient recovery of valuable metals from wastewater due to its attractive features. In this review, we first briefly summarize the sustainable supply chain and significance of sustainable recovery of aqueous high-value metals. Then, we review the most recent advances and application potential in promising state-of-the-art membrane-based technologies for recovery of high-value metals (silver, gold, rhenium, platinum, ruthenium, palladium, iridium, osmium, and rhodium) from wastewater effluents. In particular, pressure-based membranes, liquid membranes, membrane distillation, forward osmosis, electrodialysis and membrane-based hybrid technologies and their mechanism of high-value metal recovery is thoroughly discussed. Then, engineering application and economic sustainability are also discussed for membrane-based high-value metal recovery. The review finally concludes with a critical and insightful overview of the techno-economic viability and future research direction of membrane technologies for efficient high-value metal recovery from wastewater.

The potential therapeutic value of the natural plant compounds matrine and oxymatrine in cardiovascular diseases.

Matrine (MT) and Oxymatrine (OMT) are two natural alkaloids derived from plants. These bioactive compounds are notable for their diverse pharmacological effects and have been extensively studied and recognized in the treatment of cardiovascular diseases in recent years. The cardioprotective effects of MT and OMT involve multiple aspects, primarily including antioxidative stress, anti-inflammatory actions, anti-atherosclerosis, restoration of vascular function, and inhibition of cardiac remodeling and failure. Clinical pharmacology research has identified numerous novel molecular mechanisms of OMT and MT, such as JAK/STAT, Nrf2/HO-1, PI3 K/AKT, TGF-ß1/Smad, and Notch pathways, providing new evidence supporting their promising therapeutic potential against cardiovascular diseases. Thus, this review aims to investigate the potential applications of MT and OMT in treating cardiovascular diseases, encompassing their mechanisms, efficacy, and safety, confirming their promise as lead compounds in anti-cardiovascular disease drug development.

Molecular Mechanism of the ß3AR Agonist Activity of a ß-Blocker.

Development of subtype-selective drugs for G protein-coupled receptors poses a significant challenge due to high similarity between subtypes, as exemplified by the three ß-adrenergic receptors (ßARs). The ß3AR agonists show promise for treating the overactive bladder or preterm birth, but their potential is hindered by off-target activation of ß1AR and ß2AR. Interestingly, several ß-blockers, which are antagonists of the ß1ARs and ß2ARs, have been reported to exhibit agonist activity at the ß3AR. However, the molecular mechanism remains elusive. Understanding the underlying mechanism should facilitate the development of ß3AR agonist drugs with improved selectivity and reduced off-target effects. In this work, we determined the structures of human ß3AR in complex with the endogenous agonist epinephrine or with a synthetic ß3AR agonist carazolol, which is also a high-affinity ß-blocker. Structure comparison, mutagenesis studies and molecular dynamics simulations revealed that the differences on the flexibility of D3.32 directly contribute to carazolol's distinct activities as an antagonist for the ß2AR and an agonist for the ß3AR. The process is also indirectly influenced by the extracellular loops (ECL), especially ECL1. Taken together, these results provide key guidance for development of selective ß3AR agonists, paving the way for new therapeutic opportunities.

Tetrahydrocurcumin Attenuates Polymyxin B Sulfate-Induced HK-2 Cells Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Mediated PERK/eIF2α/ATF4/CHOP Signaling Pathway Axis.

The clinical application of polymyxin B (PMB) is limited by its nephrotoxic effects, making the reduction of PMB-induced nephrotoxicity has become a pressing concern for clinicians. Tetrahydrocurcumin (THC), known for its beneficial characteristics in biological functions, presents an attractive option for intervention therapy to mitigate PMB-induced nephrotoxicity. However, the underlying mechanism of how THC mitigates PMB-induced nephrotoxicity is still poorly understood. Here, we first evaluated the potential of THC intervention therapy to mitigate PMB-induced nephrotoxicity in an in vitro model of PMB-induced cell injury. Moreover, we demonstrated that THC effectively protected HK-2 cells from PMB-induced apoptosis by using cell counting kit-8 and flow cytometry assay. THC could also suppress PMB-induced endoplasmic reticulum (ER) stress via PERK/eIF2α/ATF4/CHOP pathway. In addition, using PERK inhibitor GSK2606414 to inhibit ER stress also alleviated PMB-induced apoptosis. Taken together, these findings provide novel insights that THC possesses the ability to alleviate PMB-induced nephrotoxicity by inhibiting the ER stress-mediated PERK/eIF2α/ATF4/CHOP axis, which sheds light on the benefits of THC as an intervention strategy to reduce PMB-induced nephrotoxicity, thus providing a potential avenue for improved clinical outcomes in patients receiving PMB treatment.

Docking Score ML: Target-Specific Machine Learning Models Improving Docking-Based Virtual Screening in 155 Targets.

In drug discovery, molecular docking methods face challenges in accurately predicting energy. Scoring functions used in molecular docking often fail to simulate complex protein-ligand interactions fully and accurately leading to biases and inaccuracies in virtual screening and target predictions. We introduce the "Docking Score ML", developed from an analysis of over 200,000 docked complexes from 155 known targets for cancer treatments. The scoring functions used are founded on bioactivity data sourced from ChEMBL and have been fine-tuned using both supervised machine learning and deep learning techniques. We validated our approach extensively using multiple data sets such as validation of selectivity mechanism, the DUDE, DUD-AD, and LIT-PCBA data sets, and performed a multitarget analysis on drugs like sunitinib. To enhance prediction accuracy, feature fusion techniques were explored. By merging the capabilities of the Graph Convolutional Network (GCN) with multiple docking functions, our results indicated a clear superiority of our methodologies over conventional approaches. These advantages demonstrate that Docking Score ML is an efficient and accurate tool for virtual screening and reverse docking.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis.

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders, inflammation, tumors, various cancers, and alopecia areata. The primary bioactive constituents, sesquiterpene coumarins, have demonstrated notable therapeutic potential against neuroinflammation. In this study, a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of F. sinkiangensis. These compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques, including calculated electronic circular dichroism (ECD). Anti-neuroinflammatory assays revealed that compounds 2, 3, and 6 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values ranging from 1.63 to 12.25 µmol·L-1.

Digital light processing printed hydrogel scaffolds with adjustable modulus.

Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 µm) and broad modulus adjusting capability (15.8-345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.

Core decompression combined with bone marrow mononuclear cells in the treatment of femoral head necrosis: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis is controversial. The purpose of this study was to conduct a meta-analysis and systematic review of the evaluation of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis, and to compare the therapeutic effect of this method with that of core decompression alone, so as to provide a basis for subsequent research and clinical treatment. METHODS: We conducted detailed searches across four databases in Embase, PubMed, Web of Science, and the Cochrane Library (up to October 2023), including eight studies with a total of 370 participants and 491 hip cases. This meta-analysis followed the Preferred Reporting Project (PRISMA) guidelines. Review Manager 5.4 was used to summarize and analyze the outcome indicators and the quality and reliability of the MAs were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). RESULTS: Eight studies were included inclusion criteria. The results of meta-analysis showed that the therapeutic effect of CD combined with BMMC on VAS was better than that of CD alone (MD =-5.32, 95%CI: -9.90, -0.74, P=0.02, I²=98%), and there was no statistically significant difference between CD combined with BMMC and CD alone in the treatment of HHS (MD =2.73, 95%CI: -2.63,8.09, P=0.32, I²=82%). We conducted sensitivity analysis, the results showed that CD joint BMMC treatment effect on the HHS is superior to the single CD (MD = 5.57, 95% CI: 1.94, 9.20, P = 0.003, I squared = 0%), both no significant differences in VAS (MD = 0.47, 95% CI: -1.74, 0.79, P=0.46, I²=83%). CONCLUSION: In this study, we found that core decompression combined with bone marrow monocyte therapy improved femoral head necrosis better than core decompression alone.

An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.

Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.

2, 9-deoxyflavonoids (= 3-aryl-1-indanones) from Aglaia odorata: Structure elucidation, biosynthetic pathway and lung protective activity.

Six previously undescribed 2, 9-deoxyflavonoids (1/2a, 1/2b, 6, and 7), along with six known compounds (3-5, and 8-10), were isolated from the twigs and leaves of Aglaia odorata. Their structures were determined by a combination of spectral analysis, ECD calculation and enzymatic hydrolysis assay. Surprisingly, (±) aglaindanone E (11a, 11b) were unexpectedly formed as the derivatives of compounds 3-6 when exposed to ambient natural light. Furthermore, the plausible biosynthetic pathway of 2, 9-deoxyflavonoids was proposed and chemically mimicked. In biological activity assay, compounds 1/2a, 1/2b, 4, and 6 showed potential protective effects in the 0.75%CSE-induced BEAS-2B cells injury model.

Metal-Organic Framework Supported Low-Nuclearity Cluster Catalysts for Highly Selective Carbon Dioxide Electroreduction to Ethanol.

It is still a great challenge to achieve high selectivity of ethanol in CO2 electroreduction reactions (CO2RR) because of the similar reduction potentials and lower energy barrier of possible other C2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm-2. By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO2-to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO2-to-EtOH.

Axially chiral dihydrophenanthrene dimers from Pholidota yunnanensis with anti-neuroinflammatory activities.

Axially chiral compounds are well known in medicinal chemistry of natural products, but their absolute configurations and bioactivities are rarely reported and studied. In this study, eleven undescribed axially chiral dihydrophenanthrene dimers, as well as twenty-five known dihydrophenanthrenes, were isolated from the entire plant of Pholidota yunnanensis. Their structures were elucidated by comprehensive spectroscopic analysis. A method for determining the absolute configurations of enantiomers was developed based on the rotational barriers and calculated ECD spectra. Additionally, the activities of all isolated compounds were assessed in LPS-induced BV-2 microglial cells. Most dihydrophenanthrenes exhibited significant NO inhibitory activities, and compound 7 showed the most potent inhibitory effect with an IC50 value of 1.5 µM, compared to the positive control minocycline. The immunofluorescence and western blot results revealed that compound 7 suppressed the expression of Iba-1, iNOS and COX-2 in LPS-stimulated BV-2 microglial cells.

Extracorporeal shock wave therapy with imaging examination for early osteonecrosis of the femoral head: a systematic review.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) is a traditional non-invasive therapy to treat osteonecrosis of the femur head (ONFH). This systematic review aims to investigate whether ESWT can improve the clinical function of ONFH and whether differences in improvement can be observed in radiographic outcomes. MATERIALS AND METHODS: Two authors independently searched PubMed, Embase, Cochrane Library, and Web of Science for English articles until October 21, 2023. After screening and reading the literature, the two authors independently used corresponding scales to evaluate the quality of the included articles and extracted data. The key data extracted included the Harris Hip Score (HHS), Visual Analog Scale (VAS), changes in lesion size, the change in the Association Research Circulation Osseous (ARCO) stage, and bone marrow edema stage. RESULTS: Nine articles included 468 males and 248 females. The average age was 43.29 years and the mean follow-up time was 15.19 months. After receiving ESWT, five studies involving 146 hips showed a higher HHS (MD=-33.38; 95%CI, -46.31, -20.45), and the difference was statistically significant (P<0.00001). The average VAS before treatment was above 5, but it dropped to 1.2 after ESWT (MD=4.64; 95%CI, 3.63, 5.64), and the difference was statistically significant (P<0.00001). Three studies found no significant differences in the areas of femoral head necrosis before and after treatment with ESWT(MD=9.66; 95%CI, -0.36, 19.67; P=0.06; I2=84%). Two articles showed that the use of ESWT had no significant effect on the change in the ARCO stage (MD=1.11; 95%CI, 0.76, 1.62; P=0.60; I2=0%). Three studies indicated that using ESWT could improve the bone marrow edema symptom in the early stage of ONFH (MD=4.35; 95%CI, 1.32, 14.37; P=0.02; I2=62%). CONCLUSION: Based on the current evidence, ESWT shows promise as a therapy to enhance hip function and alleviate pain in the early stage of ONFH. With the advancement of more precise imaging techniques, ESWT can potentially reduce the area affected by ONFH. However, such reduction was not found to be statistically significant at the imaging level. Additionally, ESWT could improve symptoms of bone marrow edema in the early stage. However, no significant change in ARCO grade was observed with ESWT treatment.