Demethyleneberberine Alleviates Pulmonary Fibrosis through Disruption of USP11 Deubiquitinating GREM1.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic interstitial lung disease. Intricate pathogenesis of pulmonary fibrosis and only two approved medications with side effects and high cost bring us the challenge of fully understanding this lethal disease and urgency to find more safe and low-cost therapeutic alternatives. PURPOSE: Demethyleneberberine (DMB) has been demonstrated to have various anti-inflammatory, antioxidant, antifibrosis and anti-cancer bioactivities. The objective of this study was to evaluate the effect of DMB on pulmonary fibrosis and investigate the mechanism. METHODS: Bleomycin (BLM)-induced pulmonary fibrosis was established in mice to evaluate the antifibrotic effect of DMB in vivo. A549 and MRC5 cells were used to evaluate the effect of DMB on epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) in vitro. High throughput sequencing, biotin-avidin system and site-directed mutagenesis were applied to explore the mechanism of DMB in alleviating pulmonary fibrosis. RESULTS: DMB alleviated BLM-induced pulmonary fibrosis in vivo by improving the survival state of mice, significantly reducing pulmonary collagen deposition and oxidative stress and improving lung tissue morphology. Meanwhile, DMB was demonstrated to inhibit epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) in vitro. High throughput sequencing analysis indicated that GREM1, a highly upregulated profibrotic mediator in IPF and BLM-induced pulmonary fibrosis, was significantly downregulated by DMB. Furthermore, USP11 was revealed to be involved in the deubiquitination of GREM1 in this study and DMB promoted the ubiquitination and degradation of GREM1 by inhibiting USP11. Remarkably, DMB was demonstrated to selectively bind to the Met776 residue of USP11, leading to disruption of USP11 deubiquitinating GREM1. In addition, DMB presented an equivalent antifibrotic effect at a lower dose compared with pirfenidone and showed no obvious toxicity or side effects. CONCLUSIONS: This study revealed that USP11/GREM1 could be a potential target for IPF management and identified that DMB could promote GREM1 degradation by inhibiting USP11, thereby alleviating pulmonary fibrosis.

The association of adverse reactions and depression in cervical cancer patients treated with radiotherapy and/or chemotherapy: moderated mediation models.

Objective: Several studies reported that adverse reactions to treatment, neuroticism, marital relations, and quality of life may impact the development of depression in cervical cancer patients treated with radiotherapy and/or chemotherapy, but the associations between them remained unclear. This study investigated the associations between these factors using moderated mediation models. Methods: Data were extracted from a survey involving cervical cancer patients treated with radiotherapy and/or chemotherapy at five tertiary hospitals in Hubei Province, China, from June to December 2022. The SPSS-PROCESS program was used to develop a moderated mediation model to study the roles of neuroticism, quality of life, and marital relations in the association between adverse reactions and depression in the study population. Results: A total of 802 cervical cancer patients treated with radiotherapy and/or chemotherapy (54.84 ± 9.68 years) were recruited. The prevalence of depression among these patients was 72.72%, with four symptom clusters of dizziness-ringing in the ears, digestive system-related symptoms, skin dryness and itching, and urinary frequency-urgency-leakage. Adverse reactions directly and positively affected the occurrence of depression, neuroticism mediated the association between adverse reactions and depression, while this association varied according to the quality of life and marital relations. Conclusion: Our findings suggest that depression is common among cervical cancer patients receiving radiotherapy and/or chemotherapy. Intervention targets for depression in cervical cancer patients should be precisely selected and targeted according to the quality of life and marital relations differences in patients, taking into account the cost of the intervention and the benefit to the patient.

Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.

BACKGROUND: Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS). METHODS: Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes. RESULTS: In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments. CONCLUSION: Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer.

BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC). METHODS: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities. RESULTS: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported. CONCLUSION: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events.

The Relationship Between Social Support and Suicide Resilience in Chinese Cancer Patients: A Serial Multiple Mediation Model Through Self-care Self-efficacy and Meaning in Life.

BACKGROUND: A growing body of literature has shown a higher risk of suicide in cancer patients compared with the general population. Early detection of factors related to suicide resilience in cancer patients could prevent loss of life. OBJECTIVE: The study aimed to investigate the serial-multiple mediation of self-care self-efficacy and meaning in life in the relationship between social support and suicide resilience among Chinese cancer patients. METHODS: A cross-sectional investigation of 287 cancer patients using a battery of self-reported questionnaires was performed. For preliminary analyses, descriptive, univariate, and Pearson correlation analyses were performed. Mediation analyses were tested using a serial-multiple mediation model (PROCESS model 6). RESULTS: Mediation analysis indicated the indirect effects of social support on suicide resilience mediated solely by either self-care self-efficacy (point estimate = 0.20; 95% confidence interval [CI], 0.12-0.30), or by meaning in life (point estimate = 0.06; 95% CI, 0.01-0.12), or by the multiple mediation of self-care self-efficacy to meaning in life (point estimate = 0.03; 95% CI, 0.01-0.06). CONCLUSIONS: The findings demonstrated the crucial direct or indirect effects of social support, self-care self-efficacy, and meaning in life on facilitating cancer patients' suicide resilience. IMPLICATIONS FOR PRACTICE: Oncology nurses, as 24-hour care providers for cancer patients, may interact with and be important sources for the psychosocial care of cancer patients at risk of suicide. Prevention and intervention efforts must be directed at assisting cancer patients, improving self-care self-efficacy, and finding meaning in life after a cancer diagnosis.

Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. ELIGIBILITY CRITERIA: Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. RESULTS: Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p<0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p<0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). CONCLUSION: Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

The prevalence of depression and suicidal ideation among cancer patients in mainland China and its provinces, 1994-2021: A systematic review and meta-analysis of 201 cross-sectional studies.

To evaluate the national prevalence depression of Chinese cancer patients and clarify its potential associated factors. Twelve databases were searched from database inception through October 31, 2022 for relevant studies published in English (PubMed MEDLINE, Ovid MEDLINE, Embase, Scopus, PsycINFO, and Cochrane and Web of Science) and Chinese (China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Biomedical Literature Service System, Duxiu) that estimated point or period prevalence of depression, depressive disorder, or suicidal ideation as assessed by self-report scale or structured interview. 201 studies were eligible for inclusion in our meta-analyses. We found the national pooled prevalence rates of depression and suicidal ideation were 44.63 % (95 % CI 42.24 %-47.01 %) and 24.95 % (95 % CI 10.96 %-38.95 %), respectively. The pooled prevalence of depression was associated with study location, cancer type, comorbid chronic disease, and female sex (all P < 0.05). The distribution of the depression prevalence among cancer patients in mainland China was characterized by significant geographical variation and clustering. The highest pooled prevalence of depression was among gynecologic oncology patients. We recommend that more attention and resources be given to mental health problems such as depression and suicidal ideation among Chinese cancer patients, and that prevention programs be developed, especially in areas with a high prevalence of depression.

Risk Factors for Revision or Rerupture After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The rerupture or need for revision after anterior cruciate ligament reconstruction (ACLR) is a serious complication. Preventive strategies that target the early identification of risk factors are important to reduce the incidence of additional surgery. PURPOSE: To perform a systematic review and meta-analysis to investigate risk factors for revision or rerupture after ACLR. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science from database inception to November 2021 and updated in January 2022. Quantitative, original studies reporting potential adjusted risk factors were included. Odds ratios (ORs) were calculated for potential risk factors. RESULTS: A total of 71 studies across 13 countries with a total sample size of 629,120 met the inclusion criteria. Fifteen factors were associated with an increase in the risk of revision or rerupture after ACLR: male sex (OR, 1.27; 95% CI, 1.14-1.41), younger age (OR, 1.07; 95% CI, 1.05-1.08), lower body mass index (BMI) (OR, 1.03; 95% CI, 1.00-1.06), family history (OR, 2.47; 95% CI, 1.50-4.08), White race (OR, 1.32; 95% CI, 1.08-1.60), higher posterolateral tibial slope (OR, 1.15; 95% CI, 1.05-1.26), preoperative high-grade anterior knee laxity (OR, 2.30; 95% CI, 1.46-3.64), higher baseline Marx activity level (OR, 1.07; 95% CI, 1.02-1.13), return to a high activity level/sport (OR, 2.03; 95% CI, 1.15-3.57), an ACLR within less than a year after injury (OR, 2.05; 95% CI, 1.81-2.32), a concomitant medial collateral ligament (MCL) injury (OR, 1.62; 95% CI, 1.31-2.00), an anteromedial portal or transportal technique (OR, 1.36; 95% CI, 1.22-1.51), hamstring tendon (HT) autografts (vs bone-patellar tendon-bone [BPTB] autografts) (OR, 1.60; 95% CI, 1.40-1.82), allografts (OR, 2.63; 95% CI, 1.65-4.19), and smaller graft diameter (OR, 1.21; 95% CI, 1.05-1.38). The other factors failed to show an association with an increased risk of revision or rerupture after ACLR. CONCLUSION: Male sex, younger age, lower BMI, family history, White race, higher posterolateral tibial slope, preoperative high-grade anterior knee laxity, higher baseline Marx activity level, return to a high activity level/sport, an ACLR within less than a year from injury, a concomitant MCL injury, an anteromedial portal or transportal technique, HT autografts (vs BPTB autografts), allografts, and smaller graft diameter may increase the risk of revision or rerupture after ACLR. Raising awareness and implementing effective preventions/interventions for risk factors are priorities for clinical practitioners to reduce the incidence of revision or rerupture after ACLR.

Combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in the treatment of knee osteoarthritis: a meta-analysis of randomised controlled trials.

OBJECTIVES: The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA). DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients with KOA. INTERVENTIONS: Use of MSCs+PRP. PRIMARY AND SECONDARY OUTCOMES: Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and adverse reactions. DATA SOURCES: PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure were searched from inception to 15 July 2021. MEASURES: The OR or weighted mean difference (WMD) of relevant outcome indicators was calculated. Study quality was evaluated using the risk-of-bias assessment tool version 2.0. Heterogeneity among studies was evaluated by calculating I2. If I2＜50%, a fixed-effect model was applied; conversely, if I2 ≥50%, a random-effect model was applied. RESULTS: Six controlled clinical trials with 493 cases were included. The meta-analysis results showed that in terms of the VAS score 3 months after treatment, MSCs+PRP had no significant effect on the reduction of the VAS score in patients with KOA compared with the control (p=0.09), hyaluronic acid (HA) (p=0.15) or PRP alone (p=0.07). MSCs+PRP was more effective in reducing the VAS score at 6 and 12 months after treatment than the control (WMD=-0.55, 95% CI -0.87 to -0.22, p<0.001), HA (WMD=-1.20, 95% CI -2.28 to -0.13, p=0.03) or PRP alone (WMD=-0.54, 95% CI -0.89 to -0.18, p=0.003). Regarding the decrease in the total WOMAC score at 3 and 6 months after treatment, MSCs+PRP showed better clinical efficacy than the control or HA alone (p<0.01). Compared with the control, MSCs+PRP exhibited no significant difference in reducing the total WOMAC score 12 months after treatment (p=0.39). There was no significant difference between MSCs+PRP and the control in terms of improvement of the KOOS 12 months after treatment (p=0.16). Compared with MSCs alone, MSCs+PRP exhibited no significant difference in the incidence of adverse reactions (p=0.22) 12 months after treatment. CONCLUSIONS: Treatment with MSCs+PRP showed good clinical efficacy in improving pain and joint function in patients with KOA. Compared with MSCs alone, there was no significant difference in the incidence of adverse reactions with MSCs+PRP. PROSPERO REGISTRATION NUMBER: CRD 42021275830.

Psychiatric Distress and Suicidal Tendencies in Adult Cancer Survivors: Verifying the Validity of the Brief Symptom Inventory-18 for Identifying Suicidal Ideation in the Hospitalized Population of Mainland China.

The Brief Symptom Inventory-18 (BSI-18) is widely used to assess psychiatric distress but has not been verified in the Chinese population. From March to April 2019, 293 hospitalized cancer patients, aged 20-87, completed the cross-sectional survey with demographics questionnaire, BSI-18, and PHQ-9. We analyzed the single suicide-related item of PHQ-9 with the full score clinical outpoint for BSI-18 and PHQ-9 using SPSS 22.0 and R 2.15, including Pearson's χ2 test and ROC curve analyses. A Pearson's χ2 test was carried out to compare the three different methods with the gold screening criteria. The p-value was correspondingly to .006, .066, .838. When the PHQ-9 ≥ 10 criteria for the BSI-18, receiver operating characteristic analysis revealed that AUC values were 0.839, optimal cut-off points for both BSI-18 ≥ 50, the sensitivity of 85.8%, and 62.5%, respectively. The BSI-18 is suitable for a screening tool for psychological distress and could also be used in clinical settings for preliminary screening of hospitalized cancer patients.

What Factors Are Associated with Symptomatic Rotator Cuff Tears: A Meta-analysis.

BACKGROUND: Rotator cuff tears are common. A previous systematic review reported on factors associated with rotator cuff tears; however, it included relatively few studies and few variables, and in addition, it had considerable heterogeneity. To identify the factors associated with symptomatic rotator cuff tears and to help guide clinicians to potentially modifiable factors, we felt a broader and more inclusive meta-analysis would be useful. QUESTIONS/PURPOSES: In this systematic review and meta-analysis, we asked what (1) demographic, (2) disease, and (3) imaging factors are associated with symptomatic rotator cuff tears? METHODS: PubMed, Embase, and Web of Science were searched, and the search period were from the inception of each database through February 2021. The keywords included "risk factor," "rotator cuff injury," "rotator cuff tears," and "rotator cuff tendinitis." All comparative studies on symptomatic rotator cuff tears were included. We considered that the diagnosis of rotator cuff tear could be made by any imaging tool (MRI or ultrasound). We considered either partial- or full-thickness tears to be a rotator cuff tear. No language restrictions were applied. Twenty-six articles from 14 countries involving 9809 individuals, consisting of 3164 patients and 6645 controls, were included. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the risk of bias of the included studies, and the highest scores were 9 and 11, respectively. The Newcastle-Ottawa Scale was used for retrospective comparative studies, and the AHRQ was used to evaluate prospective comparative studies. The eight retrospective comparative studies we included were scored from 4 to 9. The quality score of the 18 prospective comparative studies ranged from 6 to 9. Publication bias was explored using the Egger test. Heterogeneity was estimated using the I2 value. If there was no heterogeneity (I2 ≤ 50%), a fixed-effects model was used to determine the overall effect size; if there was heterogeneity (I2 > 50%), a random-effects model was used to merge the effect values. A meta-analysis was performed with RevMan 5.3, and the risk ratio (RR) and weighted mean difference of related factors were calculated. RESULTS: Our meta-analysis identified the following demographic factors associated with an increased risk of rotator cuff tears: older age (mean difference 3.1 [95% CI 1.4 to 4.8]; p < 0.001), greater BMI (mean difference 0.77 [95% CI 0.37 to 1.17]; p < 0.001), smoking (RR 1.32 [95% CI 1.17 to 1.49]; p < 0.001), dominant arm (RR 1.15 [95% CI 1.06 to 1.24]; p < 0.001), greater height (mean difference 0.9 [95% CI 0.4 to 1.4]; p < 0.001), and heavier weight (mean difference 2.24 [95% CI 0.82 to 3.66]; p = 0.002). Regarding disease factors, we found that traumatic events (RR 1.91 [95% CI 1.40 to 2.54]; p < 0.001) and hypertension (RR 1.50 [95% CI 1.32 to 1.70]; p < 0.001) were associated with symptomatic rotator cuff tears. Regarding imaging factors, we found that the following three factors were associated with symptomatic rotator cuff tears: greater acromion index (mean difference 0.11 [95% CI 0.06 to 0.16]; p < 0.001), greater critical shoulder angle (mean difference 1.9 [95% CI 1.5 to 2.3]; p < 0.001), and smaller glenoid version angle (mean difference -1.3 [95% CI -1.9 to -0.8]; p < 0.001). We found no association between the patient's sex or the presence or absence of thyroid disease and the likelihood of a rotator cuff tear being present. CONCLUSION: This study identified several factors associated with symptomatic rotator cuff tears, including blood glucose, blood pressure, weight, and smoking. Clinicians may seek to modify these factors, possibly in patients with symptomatic rotator cuff tears, but also in symptomatic patients who have not yet been diagnosed with rotator cuff tears because there would be no harm or risk associated with modifying any of the factors we identified. Future research should further study whether addressing these factors can delay the progression and size of rotator cuff tears.Level of Evidence Level III, prognostic study.

Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To perform a network meta-analysis to evaluate clinical efficacy and treatment-related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs), and saline (placebo) during 6 and 12 months of follow-up. METHODS: Six databases were searched for randomized controlled trials. Outcome assessment included the visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscore, WOMAC score, International Knee Documentation Committee (IKDC) subjective score, and treatment-related AEs. Main inclusion criteria were at least one of the aforementioned outcome measurements, a minimum follow-up period of 5 months, and >80% patient follow-up. Treatments combined with the use of other operations or drugs were excluded. RESULTS: Forty-three studies meeting the eligibility criteria were included. At 6 months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option (surface under the cumulative ranking curve [SUCRA] = 96.7%, SUCRA = 85.3%, respectively). According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment (SUCRA = 86.0%, SUCRA = 80.5%, respectively). At 12 months, only AD-MSCs were associated with improved VAS scores compared with the placebo (weighted mean difference [WMD] = -20.93, 95% credibility interval [CrI], -41.71 to -0.78). Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores (WMD = -30.08; 95% CrI, -53.59 to -6.25; WMD = -34.85; 95% CrI, -68.03 to -4.86, respectively). For WOMAC scores, LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis was performed (WMD = -35.26; 95% CrI, -64.99 to -6.01; WMD = -38.69; 95% CrI, -76.21 to -2.76). LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo (WMD = 13.67; 95% CrI, 4.05-23.39). Regarding safety, all treatments except for LP-PRP (relative risk = 1.83; 95% CrI, 0.89-4.64) increased treatment-related AEs compared with the placebo. CONCLUSIONS: Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval makes it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice; although the AEs of these treatments are not serious, they may affect treatment compliance and satisfaction. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

The clinical efficacy of leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of platelet-rich plasma (PRP) in the arthroscopic treatment of rotator cuff injury has been reported in the literature. However, conclusions have been inconsistent and more often related to differences in the types of PRP used. Therefore, to minimize these differences, we performed a meta-analysis of only studies investigating leukocyte-poor PRP to evaluate whether PRP promotes and improves the effects of arthroscopic rotator cuff repair. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was conducted to evaluate the efficacy of leukocyte-poor PRP in arthroscopic rotator cuff repair. The available data were extracted, and the methodologic quality of the included studies was evaluated by the Cochrane risk-of-bias assessment tool. RESULTS: In total, 10 randomized controlled trials involving 742 patients were included. The results of the meta-analysis showed that treatment with leukocyte-poor PRP performed better than the control treatment in relieving postoperative pain in the short-term (mean difference [MD], -0.57; 95% confidence interval [CI], -0.79 to -0.35; P < .0001) and medium- and long-term (MD, -0.18; 95% CI, -0.34 to -0.03; P = .02) follow-up groups. However, the changes in the MD in the visual analog scale score were below the minimal clinically important difference. Regarding the Constant shoulder (MD, 3.35; 95% CI, 1.68-5.02; P < .0001) and University of California, Los Angeles (MD, 1.73; 95% CI, 0.94-2.52; P < .0001) scores, statistically significant differences were found in favor of leukocyte-poor PRP over the control treatment. However, the changes in the MD in both the Constant and University of California, Los Angeles scores were below the minimal clinically important difference. Moreover, during medium- and long-term follow-up, the retear rate in the leukocyte-poor PRP group was lower than that in the control group regardless of the rotator cuff tear size (small and medium [<3 cm] [risk ratio (RR), 0.64; 95% CI, 0.43-0.97; P = .03] vs. medium and large [>3 cm] [RR, 0.51; 95% CI, 0.34-0.77; P = .001]) and surgical repair method (single-row repair [RR, 0.61; 95% CI, 0.43-0.87; P = .007] vs. double-row suture bridge repair [RR, 0.57; 95% CI, 0.38-0.84; P = .005]). CONCLUSION: According to our study, leukocyte-poor PRP can significantly reduce the postoperative retear rate in the medium and long term regardless of the tear size and the method used for rotator cuff repair. However, the use of leukocyte-poor PRP failed to show clinically meaningful effects in terms of postoperative pain and patient-reported outcomes.

Evaluation of Glypican-3 Expression in Hepatocellular Carcinoma by Using IDEAL IQ Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To investigate the value of iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ) and gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for evaluating Glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy-six patients with histopathologic diagnosis of HCC were retrospectively included in this study. In all patients IDEAL IQ and Gd-EOB-DTPA-enhanced MRI were performed preoperatively using a 3 T MRI system. For an identical slice through the liver of each patient a region of interest was drawn on the tumor in the hepatobiliary phase image and copied to the R2* map and fat fraction map produced by IDEAL IQ. A Mann-Whitney U test was used to compare the region of interest values of R2*, fat fraction and uptake of Gd-EOB-DTPA values between patients with positive and negative GPC3 expression HCC. Receiver operating characteristic analysis was used to determine the diagnostic performances of each of the MRI parameters in evaluating GPC3 expression and histological grade in HCC. RESULTS: R2* value was significantly higher in cases of positive than negative GPC3 expression HCCs (p < 0.001), whereas there were no significant differences in fat fraction and uptake of Gd-EOB-DTPA between the 2 groups (both p > 0.05). R2* value had higher areas under receiver operating characteristic (0.881), sensitivity (85.96%), and specificity (84.21%) compared to the fat fraction and uptake of Gd-EOB-DTPA. CONCLUSION: R2* value yielded from IDEAL IQ could reliably predict GPC3 expression in HCC prior to surgery.

A study of the epidemiology and risk factors for attempted suicide and suicide among non-psychiatric inpatients in 48 general hospitals in Hubei province, China, 2015-2017.

OBJECTIVE: This was a large-scale epidemiological survey of non-psychiatric inpatient attempted suicides/suicides in general hospitals in China, allowing a detailed quantitative analysis of the characteristics of inpatient attempted suicides/suicides. METHODS: The incidence, inpatient demographic and behavioral characteristics, and risk factors for attempted suicide/suicide were explored through a survey of non-psychiatric inpatients admitted to 48 general hospitals, between 2015 and 2017. A Vector Error Correction model was established to explore hospital variables as predictors of inpatient attempted suicide/suicide using the annual numbers of inpatient attempted suicides/suicides, undergraduate or above nurses per total number of nurses, and number of beds per nurse in a tertiary general hospital, between 1998 and 2017. RESULTS: The incidence of attempted suicide/suicide among inpatients in general hospitals was 3.26/100,000 admissions. 180 inpatient attempted suicides/suicides were reported, which were associated with particular inpatient demographic and behavioral characteristics and a specific temporal and spatial distribution. Incidence of attempted suicide/suicide was higher in inpatients aged ≥60 years, with junior high school or lower level of education, in secondary general hospitals, suffering from malignant tumors or chronic diseases. Number of beds/nurse had a significant impact on the incidence of inpatient attempted suicide/suicide. CONCLUSION: We recommend that general hospital administrators establish a targeted approach to inpatient suicide prevention efforts in their hospitals.

Relationship of Suicidal Ideation With Demoralization, Depression, and Anxiety: A Study of Cancer Patients in Mainland China.

Demoralization is a form of psychological distress that may cause suicidal ideation. Demoralization syndrome is common among cancer patients, but there has been little empirical study on the association of suicidal ideation with demoralization, depression, and anxiety in this population. This study aims to investigate the prevalence of high demoralization among cancer patients in mainland China and the contribution of high demoralization to suicidal ideation beyond the impact of self-report depression and anxiety. In this cross-sectional study, 303 patients with cancer were invited to complete questionnaires. In total, 14.5% participants reported suicidal ideation and 49.50% high demoralization. Logistic regression analysis identified high demoralization as an independent risk factor for suicidal ideation. Only depression (odds ratio [OR], 6.68) had a stronger influence on suicidal ideation than demoralization (OR, 5.85), and patients with both depression and high demoralization were most likely to experience suicidal ideation. These findings suggest that measures of demoralization can help identify cancer patients at high suicide risk and that such patients require further attention and measures targeting demoralization for suicide prevention.

Use of statins and the risk of delirium in critically ill and surgical patients: Protocol of a systematic review and meta-analysis.

BACKGROUND: The critically ill and surgical patients are at significant risk of delirium, which is associated with a high morbidity and mortality. The association between statin use and the incidence of delirium is still controversial. In this article, we will perform a systematic review and meta-analysis of published studies to evaluate the effectiveness of statins for the prophylaxis of delirium among critically ill and surgical patients. METHODS: We will conduct a systematic literature search in EMBASE, PubMed, and the Cochrane Library from inception date to October 2018 for randomized controlled trials (RCTs) and observational studies (either cohort or case-control studies) investigating the association between use of statins and delirium risk. The Cochrane Collaboration's tool for evaluating the risk of bias and Newcastle-Ottawa scale (NOS) will be used to assess the methodological quality of RCTs and observational studies, separately. The primary outcome will be the risk of incident delirium associated with statin use. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) will be calculated by a random-effects or fixed-effects model according to heterogeneity among included studies. Subgroup analyses, meta-regression method, and assessment of publication bias will be also performed. Statistical analyses will be conducted with RevMan (version 5.3.5) and Stata (version 14.0) software. In addition, the grading of recommendations assessment, development and evaluation (GRADE) approach will be applied to evaluate the quality of evidence. RESULTS: The study will provide a high-quality synthesis and evaluate the effectiveness of statins for delirium prevention among critically ill and surgical patients. CONCLUSIONS: The systematic review and meta-analysis will provide convincing evidence concerning the effect of statins against delirium in critically ill and surgical patients.

The efficacy and safety of knotless barbed sutures in total joint arthroplasty: a meta-analysis of randomized-controlled trials.

BACKGROUND: The knotless barbed sutures (KBS) are an innovative type of suture that can accelerate the placement of sutures and eliminate knot tying. Whether the KBS are safe and efficient in total joint arthroplasty (TJA) remains controversial. Therefore, we conducted a meta-analysis to evaluate its efficacy and safety. METHODS: Randomized-controlled trials (RCTs) were identified from the PubMed, Embase, and Cochrane Library databases up to October 2017. The Cochrane risk of bias tool was used to assess methodological quality. The statistical analysis was performed with RevMan 5.3.5 software. RESULTS: A total of five RCTs (600 participants) were included in our meta-analysis. The results showed that KBS reduced wound suture time (MD - 4.51, 95% CI - 5.37 to - 3.66, P < 0.00001) and the wound suture cost (MD - 282.63, 95% CI - 445.32 to - 119.95, P < 0.00001), and did not significantly increase the rate of complications (OR 0.77, 95% CI 0.42-1.39, P = 0.13) or intraoperative events (OR 0.86, 95% CI 0.04-17.28, P = 0.92). There were no significant differences in ROM at postoperative 6 weeks and 3 months (MD - 0.74, 95% CI - 4.19 to 2.71, P = 0.67; MD - 0.30, 95% CI - 2.62 to 2.02, P = 0.80; respectively). CONCLUSION: Our findings suggest that KBS are a safe and effective method for TJA. Given the possible biases, adequately powered and better designed studies with longer follow-up are required to reach a firmer conclusion.

Coping styles and social support among depressed Chinese family caregivers of patients with esophageal cancer.

OBJECTIVES: To determine the coping styles of family caregivers of patients with esophageal cancer and examine the relationships between depression, coping styles and social support. METHODS: A descriptive and correlational survey was conducted in three university-affiliated oncology and thoraco-cardiac surgery departments in Shiyan, China. A convenience sample of 301 Chinese family caregivers of hospitalized patients with esophageal cancer were asked to respond to a set of four questionnaires including: Socio-demographic questionnaire, Center for Epidemiological Studies Depression, Brief COPE Inventory, and Multidimensional Scale of Perceived Social Support. RESULTS: For the positive coping style, male caregivers used more problem-coping than female caregivers. However, for negative coping, both male and female caregivers used maladaptive coping styles. There were significant correlations between emotion-focused coping styles with adaptive coping, maladaptive coping, depression and social support. CONCLUSIONS: Family caregivers play a major role in caring for cancer patients and suffer from various psycho-social problems. What is lacking in the literature was to address the cultural differences in cancer caregiving burden, roles, and appropriate interventions to help them face the multiple demands of caregiving. Therefore, a need to develop and evaluate interventions using randomized clinical trials and sensitive instruments to measure the effectiveness of the intervention on patients' and caregivers' outcomes.

Intestinal epithelial barrier disruption through altered mucosal microRNA expression in human immunodeficiency virus and simian immunodeficiency virus infections.

UNLABELLED: Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4(+) T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5'-3'-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE: MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of miRNA biogenesis machinery during infection. These findings suggest that the disruption of miRNA in the small intestine likely plays a role in intestinal enteropathy during HIV infection.