FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity.

Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.

Effects of contralateral versus ipsilateral electroacupuncture for analgesia and rehabilitation after unilateral total knee arthroplasty: a randomized controlled trial.

PURPOSE: Total knee arthroplasty (TKA) is a treatment for advanced knee osteoarthritis. Since postoperative pain affects rehabilitation, this study aimed to determine whether electroacupuncture (EA) contralateral to the surgical site is more effective than ipsilateral EA or sham EA in terms of relieving postoperative pain and promoting post-TKA rehabilitation. METHODS: In this parallel, single-blind randomized controlled trial, 114 patients undergoing unilateral TKA were assigned to the contralateral EA (EA on the contralateral side + sham EA on the ipsilateral), ipsilateral EA (EA on the ipsilateral + sham EA on the contralateral side), or sham EA (sham EA on both sides) groups (n = 38 each). Treatment was performed once daily on postoperative days 1-3. The visual analog scale (VAS) scores, additional opioid doses via patient-controlled analgesia (PCA) pump, Hospital for Special Surgery (HSS) knee scores, active/passive range of motion (AROM/PROM), swelling around the knee joint, and Hamilton anxiety scale (HAMA) scores were used for postoperative evaluation. RESULTS: At 3 days postoperatively, the VAS scores, HSS scores, AROM/PROM, swelling around the knee, and HAMA scores in the contralateral EA and ipsilateral EA groups were significantly improved compared with baseline. In addition, VAS scores, HSS scores, PROM and swelling around the knee were significantly better in the contralateral and ipsilateral EA groups than in the sham EA group, but similar in the two true EA groups. Furthermore, PCA additional dose release was significantly higher in the sham EA group than in the two true EA groups (which did not significantly differ). At 10 days postoperatively, the HSS scores, AROM/PROM, and HAMA scores were better in the contralateral and ipsilateral EA groups than in the sham EA group, but similar in the two true EA groups. CONCLUSION: Contralateral EA is more effective than sham EA for treating postoperative pain following TKA, but has an analgesic effect similar to that of ipsilateral EA. TRIAL REGISTRATION NUMBER: ChiCTR1800020297 (Chinese Clinical Trial Registry).

[Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats].

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity.

Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.

The incidence and risk factors for femoral head necrosis after femoral neck fracture in pediatric patients: a systematic review and meta-analysis.

BACKGROUND: The incidence of avascular necrosis (AVN) after pediatric femoral neck fracture (PFNF) in the literature varies widely, and the risk factors associated with AVN after PFNF are controversial. Therefore, this study aimed to accurately investigate the incidence of AVN after PFNF and systematically evaluate and meta-classify their risk factors. METHODS: A comprehensive search was performed of PubMed, Web of Science, and Embase. The pooled rate and 95% confidence interval (CI) were used to assess the incidence of AVN after PFNF, and pooled odds ratio (OR) were calculated to measure the effect sizes. In addition, we performed subgroup, stratified, and publication bias analyses. RESULTS: A total of 30 articles were included in our meta-analysis, with 303 AVN cases among 1185 patients. The pooled incidence of AVN after PFNF was 22% (95% CI 18%, 27%). Subgroup analyses indicated Delbet type I-IV fracture incidences with AVN of 45%, 32%, 17%, and 12%, respectively. The incidence of AVN after PFNF in Asia was 19%, lower than in Africa at 36%, Europe at 26%, and North America at 23%. In addition, the larger sample size group and the earlier published literature group showed a higher incidence of necrosis. Stratified analyses showed that patient age and Delbet fracture classification were both important factors affecting AVN after PFNF (OR = 1.61, p = 0.02 and OR = 3.02, p < 0.001, respectively), while the time to treatment was not (OR = 0.9, p = 0.71). CONCLUSION: The pooled incidence of AVN after PFNF was ~ 22%; furthermore, the available evidence demonstrates that patient age and Delbet type of fracture were important influencing factors of AVN after PFNF.

Geriatric Nutritional Risk Index as a Prognostic Factor of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

Geriatric nutritional risk index (GNRI), a newly developed indicator of nutritional status retrieved by serum albumin concentration and ideal body weight, has been suggested as a prognostic factor for various malignancies. The aim of the study was to summarize the prognostic role of GNRI for patients with non-small cell lung cancer (NSCLC) in a meta-analysis. Cohort studies evaluating the relationship between GNRI at baseline and survival OF NSCLC were retrieved by search of PubMed, Embase, and Web of Science databases from inception to January 12, 2022. A conservative random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. Eleven cohorts including 2865 patients with NSCLC were included. Compared to those with higher GNRI, NSCLC patients with lower GNRI were associated with poorer overall survival [OS, hazard ratio (HR): 2.39, 95% CI: 1.97-2.91, p<0.001; I2=29%), progression-free survival (HR: 1.94, 95% CI: 1.52-2.47, p<0.001; I2=29%), and cancer-specific survival (HR: 2.59, 95% CI: 1.55-4.35, p<0.001; I2=0%). Subgroup analyses showed that the significant association between lower GNRI and worse OS in patients with NSCLC was not affected by study characteristics including study location, design, cancer stage, treatment, or follow-up durations (p for subgroup effects all<0.001). In conclusion, a lower GNRI in patients with NSCLC may be a predictor of poor survival. Nutritional status indicated by GNRI may be important for the prognostic prediction of patients with NSCLC.

Bioresponsive Nanomaterials: Recent Advances in Cancer Multimodal Imaging and Imaging-Guided Therapy.

Cancer is a serious health problem which increasingly causes morbidity and mortality worldwide. It causes abnormal and uncontrolled cell division. Traditional cancer treatments include surgery, chemotherapy, radiotherapy and so on. These traditional therapies suffer from high toxicity and arouse safety concern in normal area and have difficulty in accurately targeting tumour. Recently, a variety of nanomaterials could be used for cancer diagnosis and therapy. Nanomaterials have several advantages, e.g., high concentration in tumour via targeting design, reduced toxicity in normal area and controlled drug release after various rational designs. They can combine with many types of biomaterials in order to improve biocompatibility. In this review, we outlined the latest research on the use of bioresponsive nanomaterials for various cancer imaging modalities (magnetic resonance imaging, positron emission tomography and phototacoustic imaging) and imaging-guided therapy means (chemotherapy, radiotherapy, photothermal therapy and photodynamic therapy), followed by discussing the challenges and future perspectives of this bioresponsive nanomaterials in biomedicine.

Polyphenolic-protein-polysaccharide conjugates from Spica of Prunella vulgaris: Chemical profile and anti-herpes simplex virus activities.

Previous studies showed that the water extract (PVW) from Spica of Prunella vulgaris Linn. (Labiatae) exerts anti-herpes simplex virus (HSV) activity. Evaluation the antiviral activity of the graded ethanol precipitations indicated that 30% ethanol precipitate (PVE30) was the active principle of water extract (PVW). Further activity-oriented separation of PVE30 through salting-out method revealed that the anti-HSV activity of P. vulgaris glycoconjugates (PVG) was more potent than PVE30 and PVW, 2-fold and 4-fold, respectively. UPLC-QTOF-MS/MS, FT-IR and NMR techniques identified PVG as a type of polyphenolic-protein-polysaccharides (PPPs) with an average molecular weight of 41.69 kDa. PVG was composed of dibenzylbutyrolactone lignan units, and rich in galacturonic acid, xylose, rhamnose, rhamnose, arabinose, glucose monosaccharide units, glutamic acid and aspartic acid. Further in vitro antiviral testing confirmed that PVG substantially and stably inhibited acyclovir (ACV) resistant HSV strains; its inhibitory action was even better than the positive control ACV. Overall, our findings support PVG as a potential drug resource for anti-HSV therapy.

Opposing and Operated Side Electroacupuncture Generates Similar Analgesic Effects on Pain after Knee Surgery.

The purpose of this study was to investigate whether opposing electroacupuncture (EA) could produce similar analgesic effects as operated side EA after knee surgery in rats. Sprague Dawley rats were randomly divided into the sham surgery group, and three surgery groups: opposing EA, operated side EA, and model. After surgery, compared with the sham surgery group, three kinds of pain behavior test methods (mechanical withdrawal threshold (MWT), cumulative pain score [CPS], and mechanical hypersensitivity of knee) were used to assess the pain behavior of the rats in the surgery groups. After knee surgery, the three surgery groups were intervened for three consecutive days: EA on the nonoperated side in the opposing EA group, EA on the operated side in the operated side EA group, and no intervention in the model group. It was shown that MWT was higher and CPS was lower in the two EA groups than in the model group on the first and second days after surgery. On the third day after surgery, MWT in the two EA groups was the highest among the 3 days, CPS was the lowest among the 3 days, and the number of nonvocalizations in rats also increased compared with the model group. Moreover, the MWT of the nonoperated side increased more in the opposing EA group than in the model and operated side EA groups. This indicated that both opposing EA and operated side EA methods can be used to relieve pain after knee joint surgery.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).

Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS: This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid（IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS: The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION: Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.

Multiple-dose tranexamic acid for perioperative blood loss in total knee arthroplasty in patients with rheumatoid arthritis：a single-blinded, randomised, parallel-controlled study protocol in China.

INTRODUCTION: This clinical trial is designed to evaluate the effect of multiple-dose tranexamic acid (TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA). METHODS AND ANALYSIS: A randomised, single-blinded, parallel-controlled study will be designed. Patients with RA (age 50-75 years) undergoing unilateral primary end-stage total knee arthroplasty will be randomly divided into group A or group B. Group A will be treated with one dose of TXA (1 g; intravenous injection 3 hours postsurgery) and group B with three doses (1 g; intravenous injection at 3, 6 and 12 hours postsurgery) after surgery. The primary outcomes will be evaluated with blood loss, maximum haemoglobin drop and transfusion rate. The secondary outcomes will be evaluated with knee function and complications. ETHICS AND DISSEMINATION: The Shanghai Guanghua Hospital of Integrated Traditional Chinese Medicine and Western Medicine Ethics Committee approved in this study in July 2019. Informed consent will be obtained from all participants. Results of the trial will be published in the Dryad and repository in a peer-reviewed journal. Additionally, deidentified data collected and analysed for this study will be available for review from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: ChiCTR1900025013.

Reverse Shoulder Arthroplasty in Patients with Rheumatoid Arthritis: Early Outcomes, Pitfalls, and Challenges.

OBJECTIVE: To evaluate the early outcomes and risk factors of reverse shoulder arthroplasty (RSA) in patients with rheumatoid arthritis (RA). METHODS: A retrospective study was performed on RA patients who had undergone RSA between January 2016 and January 2018. Preoperative glenohumeral joint damage was evaluated according to two radiographic classification systems. The severity of joint damage was estimated using Larsen's method, while the Levigne-Franceschi method was used to assess the type of destruction. Further, we recorded intra- and postoperative complications. Visual Analogue Scale (VAS) was used to assess the degree of shoulder pain while shoulder function was evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score. In addition, patients' subjective outcome and range of shoulder motion were recorded. Radiographs were taken and examined during the follow-up period. Paired t-test was used to determine the difference in measurement data between preoperative and the last follow-up. VAS was analyzed using the Wilcoxon matched-pairs signed-rank test. RESULTS: A total of 14 patients with 14 shoulders were included. All the patients were female with an average age of 60.29 years (range, 49-71 years) at the time of surgery and an average RA disease duration of 24.57 years (range, 5-40 years). Seven of the 14 patients had a history of joint surgery related to RA. Meanwhile, 11 of the 14 shoulders showed glenoid bone defect, and eccentric reaming was performed intraoperatively to avoid base plate malposition. The mean follow-up period for the 14 patients was 2.76 years (range, 2-4 years). The mean VAS decreased from a value of 5.71 ± 1.10 preoperatively to 1.36 ± 0.61 postoperatively (P < 0.001). On the contrary, the ASES score showed an increase from 33.93 ± 6.89 to 76.67 ± 5.23 (P < 0.001). An increase in active forward elevation, abduction, and external rotation with the arm in 90° of abduction from 85.71° ± 17.61°, 77.14° ± 19.43°, and 17.14° ± 10.97° to 126.43° ± 5.23°, 106.42° ± 11.72°, and 38.57° ± 14.57°, respectively, was observed (P < 0.001). Subjective outcome assessment showed that 13 of the 14 patients were very satisfied or satisfied with the operation, while one patient was uncertain due to co-existing ipsilateral elbow lesion. Notably, one patient acquired a humeral periprosthetic fracture during the operation. In this study, no major complications such as periprosthetic joint infection and dislocation or implant loosening were observed. Further, no patients underwent revision for any reason at the end of the follow-up. CONCLUSIONS: RSA could achieve good early outcomes without high complication rates in patients with RA. Glenoid bone defects and adjacent joints involvement were common in this patient group, which might increase the risk of surgery and affect postoperative satisfaction.

Using electroacupuncture to recover muscle strength in patients with knee osteoarthritis after total knee arthroplasty: a study protocol for a double-blinded, randomized, and placebo-controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is a gold standard for patients with terminal term gonarthrosis for reducing pain, correcting deformities, and regaining stability. However, post-TKA muscle strength recovery is often difficult. Although electroacupuncture (EA) enhances lower extremity muscle strength of the lower extremity, there is limited evidence regarding its effect on lower extremity muscle strength in post-TKA patients. Consequently, this trial intends to evaluate the efficacy of post-TKA EA on the recovery of lower extremity muscle strength, specifically, during the early post-TKA period. METHODS/DESIGN: This is a double-blinded, randomized, and controlled trial. It will be conducted between August 2020 and December 2020. Ninety-four participants with KOA who have undergone unilateral TKA will be randomized into a treatment (EA) group and a control (sham EA) group. The former and latter groups will receive EA and sham EA, respectively, at ST37, ST36, SP10, and SP9 acupoints. The participants will undergo ten treatment sessions over 2 weeks (5 sessions per week). The primary outcomes will include changes in muscle strength and the Hospital for Special Surgery score at the second week from baseline (pre-op 1 day or POD 3). The secondary outcomes will include a 4-m walk test, numerical rating scale score, the Hamilton Anxiety Scale score, and additional analgesia use. Additional outcomes will include the incidence of analgesia-related side effects and the participant satisfaction rate. Participant blinding will also be assessed where they will be asked to guess whether they received EA after the latest intervention. Adverse EA events will be documented and assessed throughout the trial. DISCUSSION: EA is helpful for post-TKA recovery and enhancement of lower limb muscle strength. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027806 . Registered on 29 November 2019.

[Clinical study on the control of intra-articular hemorrhage by tranexamic acid after shoulder arthroscopy].

OBJECTIVE: To explore clinical effects of tranexamic acid on postoperative intra-articular hemorrhage after shoulder arthroscopy. METHODS: From February to July 2018, 60 patients with rotator cuff tears treated by shoulder arthroscopy were randomly divided into observation group and control group, 30 cases in each group. In observation group, there were 6 males and 24 females; aged from 55 to 70 years old with an average age of (62.3±5.5) years; the courses of disease ranged from 2 to 36 months with an average of (11.7±1.7) months; received 0.5 g tranexamic acid (1 g of tranexamic acid was diluted with normal saline to 20 ml) in each articular cavity and subacromial space after operation. In control group, there were 5 males and 25 females; aged from 56 to 72 years old with an average of (63.4±5.8) years old; the courses of disease ranged from 4 to 36 months with an average of (10.8±1.4) months; 10 ml of normal saline was injected into joint cavity and subacromial space. Hemoglobin values between two groups before and after operation at 1 day were recorded, circumference of shoulder joint was measured preoperatively and the 1st and 7th days after operation, and circumference difference of shoulder joint was recorded. Complications such as subcutaneous blood stasis and DVT were recorded. RESULTS: There was no significant difference in hemoglobin values between two groups before and after operation at 1 day (P>0.05) . On the first day after surgery, peripheral diameter of shoulder joint in observation group [(32.9±0.3) cm ] was significantly lower than that in control group [(35.1±0.5) cm ], and the circumference difference of shoulder joint in observation group [(8.7±0.4) mm ] was also significantly lower than that in control group [(12.3±0.5) mm ], the difference was statistically significant (P<0.05) . However, there was no significant difference in circumference of shoulder joint and the difference in circumference of shoulder joint between two groups on the 7th day after operation (P>0.05) . Two patients in observation group occurred subcutaneous ecchymosis, while 6 patients occurred in control group, but without statistical difference between two groups (P>0.05) . CONCLUSION: Subacromial and articular injection of tranexamic acid could significantly reduce early swelling of soft tissue after arthroscopic shoulder surgery, and it has better safety.

Zoledronic acid ameliorates the effects of secondary osteoporosis in rheumatoid arthritis patients.

BACKGROUND: Secondary osteoporosis may occur in patients with rheumatoid arthritis (RA), causing irreversible joint damage and disability. Bisphosphonates, the recently developed bone resorption inhibitors, have demonstrated significant therapeutic effects on senile and postmenopausal osteoporosis. This study evaluated the efficacy and safety of zoledronic acid (ZOL), with or without methotrexate (MTX), for the prevention and treatment of bone destruction in RA patients. METHODS: We recruited 66 RA patients with symptoms of secondary osteoporosis. They were randomized into three treatment groups-combined treatment with MTX and ZOL, ZOL monotherapy, or MTX monotherapy-in two consecutive 6-month periods. The participants were followed for 12 months. At the end of each treatment period, improvement in disease activity, bone destruction, and fracture risk were evaluated. RESULTS: Combined treatment with ZOL and MTX had significantly better clinical efficacy compared with either ZOL or MTX monotherapy (P < 0.05). The combination significantly improved the lumbar spine and hip BMD and reduced FRAX scores, suggesting that ZOL combined with MTX reduces bone loss and risk of hip fracture in RA patients with secondary osteoporosis. CONCLUSION: ZOL has a synergistic effect when combined with MTX, inhibiting RA disease activity, reducing fracture risk, and improving quality of life in RA patients with secondary osteoporosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019290. Registered 3 November 2018-Retrospective registered, http://www.chictr.org.cn/showproj.aspx?proj = 31758.

Efficacy of different-frequency TEAS on acute pain after the total knee arthroplasty: a study protocol for a parallel group randomized trial.

BACKGROUND: Total knee arthroplasty (TKA) is an optimal option for patients with middle-to-end-stage knee osteoarthritis. However, the management of postoperative acute pain remains inefficient. Transcutaneous electrical acupoint stimulation (TEAS) is a nonpharmacological method to manage postoperative acute pain. Different frequencies of TEAS have been tested using varying parameters, but the optimal analgesic frequency remains controversial. The aim of this study was to explore the optimal analgesic frequency of TEAS for treating acute pain after the primary unilateral TKA. METHODS/DESIGN: This is a double-blind, randomized controlled trial. A total of 156 patients are randomly assigned to: G1, 5 Hz TEAS; G2, 100 Hz TEAS; G3, mixed TEAS (alternative use of daily 5 Hz and 100 Hz TEAS) and G4, placebo TEAS. In the G1, G2 and G3 groups, TEAS is conducted at acupoints SP9 and GB34 of the leg that was operated on (at a wave of continuous, balanced and asymmetrical biphasic square, with a pulse width of 200 µs, and a strong but comfortable current) for 30 min prior to a 30-min rehabilitation session per day for 2 weeks. In G4 group, TEAS is delivered at a strong but comfortable current for 30 s, then the current is gradually decreased to none over the next 15 s. The primary outcomes are measured before surgery, at baseline (POD 3, before TEAS intervention), week 1 and 2 after TEAS intervention with the Numeric Pain Rating Scale and The American Knee Society Score. The secondary outcomes include: (1) Active range of motion of the knee that was operated on; (2) Surface electromyography of both quadriceps; (3) Modified 30-s sit to stand test; (4) Additional usage of analgesia; and (5) SF-36. The additional outcomes include: (1) Patients' satisfaction rate; (2) Patient's expectation rate; and (3) Incidence of analgesia-related side effects. To test the blinding of participants and assessors, they are asked to guess whether the subjects received active or placebo TEAS within 5 min after the latest intervention. The safety and financial cost of TEAS are assessed. DISCUSSION: Mixed TEAS has more favorable effect on acute pain control than the placebo or 5 Hz or 100 Hz TEAS. TRIAL REGISTRATION: ChiCTR1800016347 . Date of registration was 26 May 2018. Retrospectively registered.

Application of electroacupuncture for postoperative pain management after total knee arthroplasty: a study protocol for a single-blinded, randomised placebo-controlled trial.

INTRODUCTION: The purpose of this study is to assess the efficacy of electroacupuncture (EA) to relieve pain and promote functional rehabilitation after total knee surgery. METHODS AND ANALYSIS: We propose a single-blinded, randomised placebo-controlled trial to evaluate the efficacy of EA. Patients with osteoarthritis (aged 55-80 years) undergoing unilateral total knee arthroplasty (TKA) will be included in the trial. They will be randomised to receive either EA or sham-EA. A total of 110 patients will receive EA and sham-EA for 3 days after TKA. Postoperative pain will be measured using visual analogue score, and the need for an additional dose of opioid and analgesics will be recorded as the primary outcome. Secondary outcomes include knee function and swelling, postoperative anxiety, postoperative nausea and vomiting among other complications. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee, and subsequent modifications of the protocol will be reported and approved by it. Written informed consent will be obtained from all of the participants or their authorised agents. TRIAL REGISTRATION NUMBER: ChiCTR1800016200; Pre-results.

Gaudichaudione H Inhibits Inflammatory Responses in Macrophages and Dextran Sodium Sulfate-Induced Colitis in Mice.

Macrophages-involved inflammation is considered to induce the damage in various diseases. Herein, novel therapeutics inhibiting over-activation of macrophages could prove an effective strategy to prevent inflammation-related diseases. Gaudichaudione H (GH), which is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae) has previously been demonstrated its anti-cancer effects on several cancer cell lines. However, no report has been published about the anti-inflammatory effect of GH to date. This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, the nuclear translocation of transcription factors NF-κB and activator protein 1 (AP-1), as well as upstream signaling of the toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) pathway in stimulated macrophages. Furthermore, the result of the intracellular signaling array showed that the phosphorylation of adenosine 5'-monophosphate-activated protein kinase-α (AMPKα), proline-rich Akt substrate of 40 kDa (PRAS40), and p38 could be down regulated by GH in BMDMs, indicating that the mechanism by which GH inhibited inflammation may be also associated with the energy metabolism pathway, PRAS40-mediated NF-κB pathway, cell proliferation, apoptosis, and autophagy, etc. In addition, GH alleviated dextran sodium sulfate (DSS)-induced colitis in mice by ameliorating weight loss, stool consistency change, blood in the stool, and colon shortening. GH decreased the protein and mRNA levels of IL-6 and TNF-α, iNOS and COX-2 mRNA expression, the activation of NF-κB and MAPK pathways, the phosphorylation of AMPKα and PRAS40, histological damage, and infiltration of macrophages in the colons of mice with DSS-induced colitis. Taken together, our results support that GH exerts the anti-inflammatory effects in macrophages in vitro through regulation of NF-κB and MAPK pathways, and DSS-induced colitis mouse model in vivo. These findings suggest that GH may be a promising candidate in treating macrophage-related inflammatory disease.

What Percentage of Patients is a Candidate for Unicompartmental Knee Replacement at a Chinese Arthroplasty Center?

BACKGROUND: Data on indication of Unicompartmental Knee Arthroplasty (UKA) in the Asian population are currently not available. The current paper evaluates patients undergoing knee replacement at a Chinese Orthopaedic Specialty Hospital to report the percentage of patients who meet radiographic and clinical indication criteria for UKA. METHODS: Over a one-year period 463 consecutive patients (515 knees) underwent primary knee replacement surgery. Clinical data were recorded and preoperative radiographs were assessed. Patients were classified as suitable candidates for UKA based on the degree of deformity, preoperative ROM and radiographic appearance of osteoarthritis. The different indication criteria for body weight and extend of patellofemoral osteoarthritis as reported by Kozinn and Scott as well as the Oxford Group were applied. RESULTS: 160 knees (31%) were excluded because of inflammatory and posttraumatic arthritis. 55 knees had to be excluded because of incomplete radiographs. Of the remaining 300 knees with osteoarthritis, 241 knees were excluded because of extend of deformity (n=156), decreased range of motion (n=119), advanced patellofemoral arthritis with bone loss (n=11) and AP instability (n=1). Of the remaining 63 knees, 54 knees (18%) met the modified Oxford criteria for mobile UKA and only 25 knees (8%) met the Scott and Kozinn criteria for fixed UKA. CONCLUSION: The current paper suggests that in comparison to Caucasian population, only a smaller percentage of patients at a Chinese Orthopaedic Specialty Hospital meet the indication criteria for UKA. Therefore, it might make sense to concentrate UKA surgeries in high volume centers.