Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Concentration-Driven Evolution of Adaptive Artificial Ion Channels or Nanopores with Specific Anticancer Activities.

In nature, ceramides are a class of sphingolipids possessing a unique ability to self-assemble into protein-permeable channels with intriguing concentration-dependent adaptive channel cavities. However, within the realm of artificial ion channels, this interesting phenomenon is scarcely represented. Herein, we report on a novel class of adaptive artificial channels, Pn-TPPs, based on PEGylated cholic acids bearing triphenylphosphonium (TPP) groups as anion binding motifs. Interestingly, the molecules self-assemble into chloride ion channels at low concentrations while transforming into small molecule-permeable nanopores at high concentrations. Moreover, the TPP groups endow the molecules with mitochondria-targeting properties, enabling them to selectively drill holes on the mitochondrial membrane of cancer cells and subsequently trigger the caspase 9 apoptotic pathway. The anticancer efficacies of Pn-TPPs correlate with their abilities to form nanopores. Significantly, the most active ensembles formed by P5-TPP exhibits impressive anticancer activity against human liver cancer cells, with an IC50 value of 3.8 µM. While demonstrating similar anticancer performance to doxorubicin, P5-TPP exhibits a selectivity index surpassing that of doxorubicin by a factor of 16.8.

Non-Covalently Stapled H+ /Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy.

The development of stimuli-responsive artificial H+ /Cl- ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H+ /Cl- across the membrane with H+ /Cl- transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC50 =8.5 µM). The mechanism underlying cancer cell death mediated by the H+ /Cl- channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 µM.

Mortality burden based on the associations of ambient PM2.5 with cause-specific mortality in China: Evidence from a death-spectrum wide association study (DWAS).

Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013-2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 µg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % [95 % confidence interval (CI): 0.73 %, 0.86 %] rise in total mortality. We found greater mortality effect at PM2.5 concentrations < 50 µg/m3. Stratified analyses showed greater ERs in females (1.01 %, 95 %CI: 0.91 %, 1.11 %), children ≤ 5 years (2.17 %, 95 %CI: 0.85 %, 3.51 %), and old people ≥ 70 years. We identified 33 specific causes (level 2) of death which had significant associations with PM2.5, including 16 circulatory diseases, 9 respiratory diseases, and 8 other causes. The PAF estimated based on the overall association between PM2.5 and total mortality was 3.16 % (95 %CI: 2.89 %, 3.40 %). However, the PAF was reduced to 2.88 % (95 %CI: 1.88 %, 3.81 %) using the associations of PM2.5 with 33 level 2 causes of death, based on which 250.15 (95 %CI: 163.29, 330.93) thousand deaths were attributable to short-term PM2.5 exposure across China in 2019. Overall, this study provided a comprehensive picture on the death-spectrum wide association between PM2.5 and morality in China. We observed robust positive cause-specific associations of PM2.5 with mortality risk, which may provide more precise basis in assessing the mortality burden of air pollution.

CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. With aging and the accumulated effects of environmental stress, retinal pigment epithelial (RPE) cells are particularly susceptible to oxidative damage, which can lead to retinal degeneration. However, the underlying molecular mechanisms of how RPE responds and progresses under oxidative damage are still largely unknown. Here, we reveal that exogenous oxidative stress led to ferroptosis characterized by Fe2+ accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1), as a component of the unfolded protein response (UPR) pathway, plays a pivotal role in oxidative-stress-induced cell ferroptosis via the regulation of glutathione depletion. These results indicate the biological significance of Chac1 as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.

Noninvasive high-frequency oscillatory ventilation versus bi-level positive pressure ventilation in premature infants with respiratory failure: A retrospective study.

Objectives: Noninvasive high-frequency oscillatory ventilation (nHFOV) is a novel respiratory support mode for premature infants. This retrospective study aimed to compare the effect of nHFOV and bi-level nasal continuous positive airway pressure (BiPAP) in premature infants with neonatal respiratory failure (NRF) as initial noninvasive ventilation (NIV) support mode. Methods: We retrospectively analyzed medical records of preterm infants admitted to the tertiary neonatal intensive care units (NICUs) of Fujian Maternal and Child Health Hospital from January 2019 to December 2020. Preterm infants with the gestational age of 25-34 weeks, diagnosed with NRF, used nHFOV or BiPAP as the initial respiratory support mode were analyzed. The rates of invasive mechanical ventilation (IMV) within the first seven days after birth and adverse outcomes were compared between the two groups. Results: Two hundred fifty-five preterm infants were analyzed (128 in nHFOV group,127 in BiPAP group). There was no significant difference in baseline characteristics between the two groups. Compared with the BiPAP group, the nHFOV group had significantly lower need for IMV within the first seven days after birth (18/128 vs. 33/127, p = 0.01) and PCO2 at 12 and 24 hours post-treatment (46.34±5.24mmHg vs. 51.18±4.83mmHg, P<0.01; 40.72±4.02mmHg vs. 42.50±3.86mmHg, P<0.01). The incidence of BPD, ROP, air leak syndromes, IVH≥ grade 3, PVL, NEC≥II stage, abdominal distension, and nasal trauma were similar between the two groups. Conclusion: nHFOV significantly reduced the need for IMV and improved the elimination of CO2 compared with BiPAP in preterm infants with NRF without increasing the incidence of adverse effects.

Tanshinone IIA reduces pyroptosis in rats with coronary microembolization by inhibiting the TLR4/MyD88/NF-κB/NLRP3 pathway.

Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague-Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 µm) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1ß, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.

Prognostic signature composed of transcription factors accurately predicts the prognosis of gastric cancer patients.

BACKGROUND: Transcription factors (TFs) are involved in important molecular biological processes of tumor cells and play an essential role in the occurrence and development of gastric cancer (GC). METHODS: Combined The Cancer Genome Atlas Program and Genotype-Tissue Expression database to extract the expression of TFs in GC, analyzed the differences, and weighted gene co-expression network analysis to extract TFs related to GC. The cohort including the training and validation cohort. Univariate Cox, least absolute contraction and selection operator (LASSO) regression, and multivariate Cox analysis was used for screening hub TFs to construct the prognostic signature in the training cohort. The Kaplan-Meier (K-M) and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive ability of the prognostic signature. A nomogram combining clinical information and prognostic signatures of TFs was constructed and its prediction accuracy was evaluated through various methods. The target genes of the hub TFs was predicted and enrichment analysis was performed to understand its molecular biological mechanism. Clinical samples and public data of GC was collected to verify its expression and prognosis. 5-Ethynyl-2'-deoxyuridine and Acridine Orange/Ethidium Bromide staining, flow cytometry and Western-Blot detection were used to analyze the effects of hub-TF ELK3 on the proliferation and apoptosis of gastric cancer in vitro. RESULTS: A total of 511 misaligned TFs were obtained and 200 GC-related TFs were exposed from them. After systematic analysis, a prognostic signature composed of 4 TFs (ZNF300, ELK3, SP6, MEF2B) were constructed. The KM and ROC curves demonstrated the good predictive ability in training, verification, and complete cohort. The areas under the ROC curve are respectively 0.737, 0.705, 0.700. The calibration chart verified that the predictive ability of the nomogram constructed by combining the prognostic signature of TFs and clinical information was accurate, with a C-index of 0.714. Enriching the target genes of hub TFs showed that it plays an vital role in tumor progression, and its expression and prognostic verification were consistent with the previous analysis. Among them, ELK3 was proved in vitro, and downregulation of its expression inhibited the proliferation of gastric cancer cells, induced proliferation, and exerted anti-tumor effects. CONCLUSIONS: The 4-TFs prognostic signature accurately predicted the overall survival of GC, and ELK3 may be potential therapeutic targets for GC.

Effectiveness of eccentric strengthening in the treatment of lateral elbow tendinopathy: A systematic review with meta-analysis.

STUDY DESIGN: Meta-analysis. INTRODUCTION: Lateral elbow tendinopathy is a common condition with an annual incidence of up to 3% of the population. Eccentric strengthening has shown promise as a method to treat lateral elbow tendinopathy, but is unclear if it is superior to other forms of treatment. PURPOSE OF THE STUDY: The purpose of this study was to investigate the effectiveness of eccentric strengthening compared with other forms of strengthening and pain-relieving modalities on pain, strength, and function in people with lateral elbow tendinopathy. METHODS: Five electronic databases were searched. Reference lists of selected articles were hand-searched. Outcomes were defined a priori. Meta-analyses were performed using a random effects model with standardized mean differences, test of heterogeneity, and sensitivity analyses. RESULTS: Eight articles were included in this review. When comparing eccentric strengthening to other forms of strengthening and pain-relieving modalities, there were significant large effect size of 1.12 (CI: 0.31-1.93) and 1.22 (CI: 0.25-2.18) in reducing pain and improving function in the short-term, respectively. In long-term, results were inconclusive on all outcomes. DISCUSSION: A treatment program using eccentric strengthening of adequate intensity and duration seemed to be most effective for treating lateral elbow tendinopathy. CONCLUSIONS: The state of science of best care for lateral elbow tendinopathy is still in its infancy. Large, high-quality randomized controlled trials with clearly defined strengthening regime are needed to determine optimal dosage to maximize treatment effects. Recommendations were provided based on careful synthesis of findings from this review and current evidence in literature.

Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3ß signaling pathway.

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 µm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3ß pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3ß pathway.

Microaneurysms detection in color fundus images using machine learning based on directional local contrast.

BACKGROUND: As one of the major complications of diabetes, diabetic retinopathy (DR) is a leading cause of visual impairment and blindness due to delayed diagnosis and intervention. Microaneurysms appear as the earliest symptom of DR. Accurate and reliable detection of microaneurysms in color fundus images has great importance for DR screening. METHODS: A microaneurysms' detection method using machine learning based on directional local contrast (DLC) is proposed for the early diagnosis of DR. First, blood vessels were enhanced and segmented using improved enhancement function based on analyzing eigenvalues of Hessian matrix. Next, with blood vessels excluded, microaneurysm candidate regions were obtained using shape characteristics and connected components analysis. After image segmented to patches, the features of each microaneurysm candidate patch were extracted, and each candidate patch was classified into microaneurysm or non-microaneurysm. The main contributions of our study are (1) making use of directional local contrast in microaneurysms' detection for the first time, which does make sense for better microaneurysms' classification. (2) Applying three different machine learning techniques for classification and comparing their performance for microaneurysms' detection. The proposed algorithm was trained and tested on e-ophtha MA database, and further tested on another independent DIARETDB1 database. Results of microaneurysms' detection on the two databases were evaluated on lesion level and compared with existing algorithms. RESULTS: The proposed method has achieved better performance compared with existing algorithms on accuracy and computation time. On e-ophtha MA and DIARETDB1 databases, the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.87 and 0.86, respectively. The free-response ROC (FROC) score on the two databases was 0.374 and 0.210, respectively. The computation time per image with resolution of 2544×1969, 1400×960 and 1500×1152 is 29 s, 3 s and 2.6 s, respectively. CONCLUSIONS: The proposed method using machine learning based on directional local contrast of image patches can effectively detect microaneurysms in color fundus images and provide an effective scientific basis for early clinical DR diagnosis.

Angiogenin, FGF-α, and IL-36ß have higher expression levels in aqueous humor of nAMD patients in comparison to cataract patients.

BACKGROUND: Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients. METHODS: This prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples were collected before the first (baseline), second (1 month later), and third (2 months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3 mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA). RESULTS: Three cytokines in aqueous humor, including angiogenin, interleukin-36ß (IL-36ß), and fibroblast growth factor-acidic (FGF-α) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients' basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3 mm, and GLD. CONCLUSIONS: Angiogenin, IL-36ß, and FGF-α have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2 months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.

Fuzzy Evaluation Output of Taste Information for Liquor Using Electronic Tongue Based on Cloud Model.

As a taste bionic system, electronic tongues can be used to derive taste information for different types of food. On this basis, we have carried forward the work by making it, in addition to the ability of accurately distinguish samples, be more expressive by speaking evaluative language like human beings. Thus, this paper demonstrates the correlation between the qualitative digital output of the taste bionic system and the fuzzy evaluation language that conform to the human perception mode. First, through principal component analysis (PCA), backward cloud generator and forward cloud generator, two-dimensional cloud droplet groups of different flavor information were established by using liquor taste data collected by electronic tongue. Second, the frequency and order of the evaluation words for different flavor of liquor were obtained by counting and analyzing the data appeared in the artificial sensory evaluation experiment. According to the frequency and order of words, the cloud droplet range corresponding to each word was calculated in the cloud drop group. Finally, the fuzzy evaluations that originated from the eight groups of liquor data with different flavor were compared with the artificial sense, and the results indicated that the model developed in this work is capable of outputting fuzzy evaluation that is consistent with human perception rather than digital output. To sum up, this method enabled the electronic tongue system to generate an output, which conforms to human's descriptive language, making food detection technology a step closer to human perception.

Factors Associated with a Large Decline in Renal Function or Progression to Renal Insufficiency in Hospitalized Atrial Fibrillation Patients with Early-Stage CKD.

Clinicians must consider renal function when administering anticoagulants for atrial fibrillation (AF). Determination of risk factors for renal function decline may enable identification of patients who require closer monitoring. We investigated the characteristics associated with renal function decline in patients with AF. The study cohort consisted of 631 AF patients who had at least one readmission during the follow-up period and stages 1-3 chronic kidney disease (CKD). The primary outcome measure was large renal function decline (≥30% decrease from baseline estimated glomerular filtration rate [eGFR]). The secondary outcome measure was a final eGFR < 60 mL/minute/1.73 m2 for those with a baseline eGFR above this level. The mean eGFR was 74.4 ± 18.5 mL/minute/1.73 m2, and the mean follow-up time was 30.2 ± 13.2 months. The primary outcome occurred in 155 patients (24.6%) and was associated with congestive heart failure (CHF), proteinuria, type of AF, and left atrial diameter (LAD) ≥ 45 mm. Among 478 patients with a baseline eGFR ≥ 60 mL/minute/1.73 m2, 137 (28.7%) progressed to renal failure (eGFR < 60 mL/minute/1.73 m2). A decreasing eGFR was associated with age ≥ 75 years, CHF, lower baseline eGFR, and LAD ≥ 45 mm. CHF, proteinuria, type of AF, and LAD ≥ 45 mm were associated with eGFR decline ≥ 30% in AF patients with CKD stages 1-3. Advanced age, CHF, lower baseline eGFR, and LAD ≥ 45 mm were associated with progression to renal insufficiency. These results should be considered when identifying patients who require more frequent monitoring of eGFR.

[Roles of G protein-coupled receptor 30 in the effects of genistein on apoptosis and cell cycle in human thyroid squamous cells SW579].

OBJECTIVE: Investigate the estrogen receptor expression in human thyroid squamous cell carcinoma SW579 and the effects of genistein on the apoptosis and cycle of SW579 and its mechnism. METHODS: The real-time PCR was applied to detect the expression of estrogen receptor(ER)α、ERß and G protein-coupled receptor(GPR)30 in human thyroid squamous cell line SW579; MTT was used to test the effect of genistein on cell proliferation in the SW579 cells before and after blocking GPR30; flow cytometry was explorited to measure the effect of genistein on the cell cycle and apoptosis in the SW579 was detected before and after blocking GPR30. RESULTS: The high concentration of genistein promoted the expression of ERß and GPR30 in the SW579 cells, but ERα was not expressed. The specific blocking of GPR30, the cell proliferation was aboviously inhibited by genistein in the SW579 cells and the cell apoptosis was markedly promoted after the GPR30 was blocked; The cell cycle was mainly blocked in G_2/M phase. CONCLUSION: Genistein can obiviously promote the cell proliferation in the SW579 cells, which may be related to the action of GPR30.

A novel staged wrist sensorimotor rehabilitation program for a patient with triangular fibrocartilage complex injury: A case report.

STUDY DESIGN: Case report. INTRODUCTION: Studies have highlighted the sensory innervations and stabilizing role of forearm muscles on wrist joint and implications to wrist sensorimotor rehabilitation. This case explored the novel incorporation of dart-throwing motion and proprioceptive neuromuscular facilitation in wrist sensorimotor rehabilitation. PURPOSE OF THE STUDY: To describe and evaluate a staged wrist sensorimotor rehabilitation program for a patient with triangular fibrocartilage complex (TFCC) injury. METHODS: The patient participated in the staged program for 9 sessions over a 3-month period. Treatment involved neuromuscular strengthening at the wrist and movement normalization of the upper extremity. Outcome measures were grip strength, visual analog scale, joint position sense, Quick Disabilities of the Arm, Shoulder and Hand, and patient-rated wrist evaluation. RESULTS: The patient showed improvement in all outcome measures. Most outcomes exceeded the established minimal clinically important difference values. DISCUSSION: The results suggest that dart-throwing motion and proprioceptive neuromuscular facilitation are beneficial in rehabilitation of TFCC injury. CONCLUSIONS: This is the first study that incorporated dart-throwing motion and proprioceptive neuromuscular facilitation in the sensorimotor rehabilitation of TFCC injury and yielded promising results. There is a need to further evaluate the program in prospective randomized controlled trial recruiting a larger group of patients with TFCC injury.