Screening of Key Part in IFN Pathway for Herpes Zoster: Evidence from Bioinformatics Analysis.

BACKGROUND: Herpes zoster is one of the most common diseases in middle and old ages, and the incidence rate is constantly increasing. Long-term, severe neuropathological pain continues to afflict the patients, causing trouble and even the inability to live a normal life. Since the occurrence and development of herpes zoster are related to many mechanisms, there is no uniform conclusion and specific treatment method, and only a limited number of people are currently vaccinated against HZ. OBJECTIVE: This study aimed at exploring the potential mechanism or biomarkers for Herpes zoster. METHODS: In this study, a data set GSE165112 containing 12 samples was downloaded, out of which, 6 samples were treated with interferon, and 6 samples were not treated. Differentially expressed genes (DEG) analysis, KEGG, GO enrichment analysis, and GSEA were carried out. RESULTS: A total of 264 DEGs were identified, including 32 uP-regulated DEGs and 232 downregulated DEGs. DEGs are mainly enriched in immune response, inflammatory response, chemotaxis, etc. Four key pathways were found to be related to HZ, including IL2-STAT5 signaling, inflammatory response, TNF-a signaling via NF-κB, and IFN-α. Moreover, ten hub genes were also identified. CONCLUSION: This study shows that exploring DEGs and pathways through bioinformatics analysis is of great significance for understanding the molecular mechanism of HZ, especially the defect of the IFN pathway. It may be helpful in improving the treatment for HZ.

Efficacy and safety of fire needle combined with cupping for acute herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

BACKGROUND: Herpes zoster and post-herpetic neuralgia showed an increasing incidence during past two decades. Most of herpes zoster and post-herpetic neuralgia patients suffered from pain, anxiety, and depression. Fire needle combined with cupping is becoming a popular way to relieve the pain caused by herpes zoster and decrease the incidence of post-herpetic neuralgia. In this study, we aim to investigating the efficacy and safety of fire needle combined with cupping for the treatment of acute herpes zoster and postherpetic neuralgia (PHN). METHODS: The literature search will be carried out in following databases: PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data. Published and unpublished controlled trials compared fire needle combined with cupping to other treatments for acute herpes zoster or PHN will be included. Data from eligible studies will be extracted by 2 independent reviewers. Different scales will be used to assess the risk of bias based on the study design. Pain intensity and PHN are primary outcomes. The final effect size will be reported using 95% confidence interval at 0.05 significance level. DISCUSSION: This review will provide certain evidence to compare the efficacy and safety of combined acupuncture and cupping with guideline recommended drug or nerve block therapy for the treatment of herpes zoster and post-herpetic neuralgia. It will potentially provide more clinical suggestions and guidelines for health care professionals, policymakers, and researchers.

Efficacy and safety of Fufang Biejia Ruangan Tablets as an adjuvant treatment for chronic hepatitis B liver fibrosis: A systematic review and meta-analysis.

BACKGROUND: Meta-analysis was used to evaluate the efficacy of Fufang Biejia Ruangan Tablets in the treatment of chronic hepatitis B (CHB) liver fibrosis. METHODS: Databases, including PubMed, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wan Fang, VIP database, Embase, and Cochrane Library were searched. The time was searched up to May 2022. The participant intervention comparator outcomes of this study were as follows: P, patients with CHB liver fibrosis; I, Fufang Biejia Ruangan Tablets; C, pharmacological placebo; O, the efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), collagen C type IV (IV-C), portal vein diameter, spleen thickness and HBV-DNA negative conversion rate. The Cochrane Risk of Bias tool, Begg's test and Egger's test were used to evaluate the methodological quality of eligible studies. A randomized controlled trial of Fufang Biejia Ruangan Tablets was used to treat CHB liver fibrosis. Three reviewers independently selected trials, extracted data, cross-checked, and performed methodological quality assessments. Data analysis was completed by Review Manager 5.3. RESULTS: Twenty-six studies with 2717 patients were included in the meta-analysis. The meta-analysis showed that Fufang Biejia Ruangan Tablets was effective by increasing the efficacy. Fufang Biejia Ruangan Tablets was more efficient in improving ALT, AST, TBIL, ALB, PIIIP, HA, LN, IV-C, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. CONCLUSION: It was shown that Fufang Biejia Ruangan Tablets can effectively improve liver function and relieve liver fibrosis, but future research should focus on rigorously designed, multicenter, and large randomized controlled trials.

Comparative effectiveness of external therapies of traditional Chinese medicine and surgical treatments in pain management of postherpetic neuralgia: A protocol for a systematic review and network meta-analysis.

BACKGROUND: As the most common long-term complication of herpes zoster (HZ), postherpetic neuralgia (PHN) is characterized by chronic, persistent, and debilitating neuropathic pain. PHN seriously harms human health and currently becomes a topic of clinical importance. To date, the common methods of pain management in PHN include external therapies of traditional Chinese medicine and surgical treatments. However, there is no high-quality or direct evidence of their comparative effectiveness. This review aims to provide a network meta-analysis to compare the efficacy of external therapies of traditional Chinese medicine and surgical treatments in the pain management of PHN. METHODS: Databases such as PubMed, Cochrane Central Register of Controlled Trials, EMBASE, China National Knowledge Infrastructure, China Biology Medicine Disc will be searched for relevant randomized controlled trials to obtain literatures on the treatment of PHN with external therapies of traditional Chinese medicine and surgical treatments, and clinical randomized controlled trials will be screened out from their inception to August 5, 2022. The participant intervention comparator outcomes of this study are as flowing: P, patients with PHN; I, external therapies of traditional Chinese medicine and surgical treatments; C, no treatment, pharmacological placebo, treatment as usual or sham acupuncture groups; O, primary outcome is pain intensity, and secondary outcomes are onset of pain relief time, quality of life, therapeutic effective rate and reverse effects. Cochrane Risk of Bias Tool will be used in assessing literature's quality. Network meta-analyses will be conducted to generate estimates of comparative effectiveness of each intervention class and rankings of their effectiveness, in terms of pain management. RESULT: This systematic review and network meta-analysis will provide evidence of the efficacy of different therapeutic methods for pain management in PHN, to show which forms of therapy are more commonly used with higher effectiveness. DISCUSSION: The results will systematically provide suggestions for medical practitioners to choose effective, time-saving and economical pain management method for PHN.

The effect of preoperative hypoalbuminemia on complications after primary hip arthroplasty.

OBJECTIVES: To explore the risk factors of preoperative hypoalbuminemia and its' effects on complications in the elderly with primary hip arthroplasty. METHODS: A total of 211 elderly inpatients who underwent hip arthroplasty were collected. All patients were divided into the control group (preoperative serum albumin ≥35 g/L) and case group (preoperative serum albumin <35 g/L). The risk factors of preoperative hypoalbuminemia and the postoperative complications were analyzed. RESULTS: Compared to controls, hypoalbuminemia patients were older (P = 0.026), had lower BMI (P = 0.045), higher cardiac function score (P < 0.0001), higher ASA scores (P = 0.023), and longer hospital stay (P < 0.001). The intraoperative albumin loss in the case group was significantly higher than that of in control group (P < 0.001), but there was no significant difference in operation time and intraoperative blood loss between the two groups (P >0.05). Compared to controls, hypoalbuminemia patients had a higher risk for any complication (P = 0.014), such as delayed wound healing, pleural effusion, and pneumonia. The risk of postoperative complications increased by 6.9% with every 1 year old is increasing (age > 60). The risk of postoperative complications in the case group was 1.89 times higher than that in the control group. CONCLUSION: Patients with older age, poor nutritional status, and more than 2 concomitant diseases are more likely to develop preoperative hypoalbuminemia. Preoperative hypoalbuminemia is related to the increased incidence of postoperative complications. Perioperative albumin loss is not only due to perioperative blood loss, but also related to vascular permeability and abnormal albumin metabolism.

Current status survey of the extramural hospital management of venous thromboembolism after total hip and knee arthroplasty in China.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication after arthroplasty. Numerous prophylactic strategies and studies to reduce VTEs have focused on the duration of the hospital stay and on few extramural hospitals. This study aimed to investigate extramural hospital management of VTE after total hip/knee arthroplasty (THA/TKA) in China with a novel survey tool. METHODS: A total of 180 patients undergoing arthroplasty, including 68 THA patients and 112 TKA patients, were enrolled in this study. All patients received anticoagulant treatment management. A survey querying VTE management and adherence, such as therapy information, understanding of anticoagulation, satisfaction with the ability of medical staff, and satisfaction with health care costs, was administered by a questionnaire (TKA/THA Patients' Experience with Anticoagulation in the Post-discharge Period) for quality improvement. RESULTS: The average age of the patients was 65.27 ± 13.62 years. All patients knew their follow-up times. 85 % of them were suggested that re-examine at the next 14 days, and the others at the next 28 days. All patients continued to visit the orthopaedic clinic after discharge without choosing other types of outpatient services, such as an anticoagulant clinic or home visit with a nurse/pharmacist or remote evaluation by telephone. A total of 96.6 % of all patients used new oral anticoagulants, and the most common treatment duration was 2-4 weeks (93.3 %). 48 % informed their physicians that they were taking anticoagulation medications when they visited ophthalmology, dentistry, dermatology, and other departments. The overall rate of satisfaction with anticoagulation management was 81.67 %, and 6.67 % of patients were not unsatisfied with their medical expenses. Patient compliance decreased with increasing follow-up time. Continuous follow-ups after discharge significantly improved patient compliance. CONCLUSIONS: These results elucidate how we can improve the quality of anticoagulation. Continuous follow-up appointments for 30 days after discharge, especially for individuals over 65 years old, significantly improved patient satisfaction and reduced the incidence of VTE and medical costs.

Surgical Masks for Protection of Health Care Personnel Against Covid-19: Results from an Observational Study.

PURPOSE: The aim of the study was to describe the use of masks among health care personnel (HCP) exposed to index cases of coronavirus disease 2019 (COVID-19), and to evaluate any association with infection rate. METHODS: We did a retrospective, observational study of HCP at Zhongnan Hospital of Wuhan University for the management of COVID-19 (before person-to-person transmission was official confirmed, no additional protection was provided). A questionnaire was given to all staff listed on the roster in the clinical regions providing care for index patients with COVID-19. All participants were surveyed regarding hand-washing and use of surgical masks and gloves and were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were analysed (Student's t test and Pearson χ2 test) for an association between infection and use of personal protective equipment. RESULTS: Exposure of a total of 299 non-infected and 30 infected staff was confirmed. None of the 149 staff who reported use of all three preventative measures (hand-washing and use of gloves and masks) became infect-ed. In contrast, all 30 of the staff who became infected had omitted at least one of the measures. Fewer staff who wore surgical masks (P=0.000003) became infected compared with those who did not. Infections rates were significantly lower in HCP from the internal medicine departments, as these personnel generally wore masks. CONCLUSION: An association was found between SARS-CoV-2 infection of HCP and the non-use of masks when working with index cases in clinical settings. We recommend that all HCP follow the strict instructions for prevention and treatment of nosocomial infection during intimate contact with COVID-19, especially staff from surgical departments.

Safety and Effectiveness of Orthopaedic Medical Staff in Providing Support in Combating the COVID-19 Pandemic: A Retrospective Investigation from Wuhan, China.

OBJECTIVE: To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID-19. METHODS: One hundred and twenty-two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID-19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS-CoV-2 RNA, SARS-CoV-2 IgM and SARS-CoV-2 IgG tests, and training and examinations on COVID-19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID-19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. RESULTS: Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID-19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID-19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. CONCLUSION: Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID-19 with adequate precautions and proper training.

The pronator teres and the flexor carpi radialis interval approach for operative fixation of ulna coronoid process fractures.

BACKGROUND: The optimal approach for the fixation of coronoid process fractures is unknown. We present the advantages and the clinical effect of the pronator teres and the flexor carpi radialis interval approach for the treatment of ulna coronoid process fractures. METHODS: The patients, who had operative treatment of closed ulna coronoid process fracture by the pronator teres and the flexor carpi radialis interval approach between January 2011 to December 2016, were studied retrospectively. Seventeen consecutive patients had received surgical fixation by screws or a mini-plate through the above approach, of whom were 16 males and one female with an average age of 36.7 years (range, 21-58 years). There were 11 cases of type II and 6 cases of type III according to the O'Driscoll classification, of which, 6 patients had combined elbow dislocation, 2 patients showed elbow instability after fixation, and one had another incision to repair the lateral collateral ligament, and received a hinged external fixator. The other patient only received a hinged external fixator for 4 weeks. Mayo Elbow Performance Score (MEPS) was used to assess the function of elbow for each patient at the final follow-up. RESULTS: Mean follow-up was 28.7 months (range, 24-38 months). Fracture union was achieved in each patient; the average time to radiologic union was 14.2 weeks (range, 12-16 weeks). At the final follow-up, the elbow extension degree of the affected side was (3.88±2.96°), reaching 98.1% of the normal side, and the flexion degree was (131.59±4.93°), reaching 98.16% of the normal side. The forearm pronation was (82.94±3.86°), reaching 94.31% of the normal side, and the supination activity was (82.12±3.82°), reaching 93% of the normal side. According to the MEPS, the functional recovery of the injured arm was assessed as excellent in 16 cases, and good in one. None of the patients showed any neurovascular or deep infections and no heterotopic ossification was found. CONCLUSIONS: The pronator teres and the flexor carpi radialis interval approach has the advantages of simplicity, safety, minimal invasion, excellent exposure, and good postoperative function recovery for ulna coronoid process fracture.

Safety and effectiveness of acupuncture for POSEIDON patients in IVF/ICSI: A protocol for systematic review and meta-analysis.

INTRODUCTION: The purpose of this paper is to evaluate the efficacy and safety of acupuncture for POSEIDON patients undergoing IVF/ICSI. METHODS: and analysis We will electronically search Pubmed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi randomized controlled trials related to acupuncture treatment for POSEIDON patients in IVF/ICSI will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by two researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The clinical pregnancy rate (CPR) and live birth rate (LBR) will be the primary outcomes. The ongoing pregnancy, miscarriage rate (MR) and adverse events will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs. ETHICS AND DISSEMINATION: The protocol of this systematic review (SR) does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: OSF Registries, DOI: 10.17605/OSF.IO/6WP2F (https://osf.io/6wp2f).

Ju Re Ba Du therapy for Postherpetic neuralgia: A protocol for systematic review and meta-analysis.

INTRODUCTION: Postherpetic neuralgia (PHN) is one of the most common types of chronic neuropathic pain, which seriously affects quality of the life because of pain severity and poor response to the currently available treatments. Ju Re Ba Du therapy as a form of acupuncture therapy which is proved to be effective in RCTs and very suitable for patients, has been used in Postherpetic neuralgia in patients for a long time, therefore a systematic review is necessary to provide available evidence for further study. METHODS AND ANALYSIS: The following databases will be searched from their inception to October 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, VIP medicine information, and CNKI (China National Knowledge Infrastructure). PRIMARY OUTCOME: pain intensity assessed on a visual analogue scale (VAS); Additional outcomes:Data will be extracted by two researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of Ju Re Ba Du therapy intervention for people with Postherpetic neuralgia. CONCLUSION: The systematic review of this study will summarize the current published evidence of Ju Re Ba Du therapy for the treatment of Postherpetic neuralgia, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OSF REGISTRATION NUMBER: September 29, 2020 osf.io/r6y9b. (https://osf.io/r6y9b).

Study on the outcome of patients with aseptic femoral head necrosis treated with percutaneous multiple small-diameter drilling core decompression: a retrospective cohort study based on magnetic resonance imaging and equivalent sphere model analysis.

BACKGROUND: Aseptic necrosis of the femoral head (ANFH) has a high incidence in the community and causes substantial problems with health as well as economic and social stress. Core decompression is the most commonly used treatment for early ANFH. Although many studies have reported on the efficacy of femoral head core decompression surgery for ANFH, there are still some shortcomings in assessing the severity of femoral head necrosis, the location distribution, and changes in necrotic lesions before and after surgery. Magnetic resonance imaging (MRI) and equivalent sphere model analysis were used to further clarify the clinical efficacy of percutaneous multiple small-diameter drilling core decompression in patients with ANFH. METHODS: From July 2013 to November 2016, 24 patients (32 cases of the hip joint) with ANFH who underwent percutaneous multiple small-diameter drilling core decompression were selected, and a retrospective analysis was conducted. MRI as well as VAS, OHS-C, and HHS scores were used to evaluate joint function in all patients before and 6, 12, and 24 months after the operation. RESULTS: Twenty-four months after the operation, 10 hips were amputated. The survival rates of alcoholic femoral head necrosis (AFNH), idiopathic femoral head necrosis (IFHN), and steroid-induced femoral head necrosis (SIFHN) patients at 24 months were 100%, 85.7% (- 2 hips), and 0.0% (- 8 hips), respectively. The MRI and equivalent sphere analysis results revealed that the anterior superior medial quadrant was the area most prone to osteonecrosis, and the posterior superior medial quadrant was the area second most prone to necrosis. After the operation, the average percentage of the AFHN necrosis area in the total volume of the femoral head decreased from 14.5 to 10.3%, and the average percentage of the IFHN necrosis area decreased from 16.3 to 9.2%; however, the average percentage of the necrosis area for SIFHN increased from 30.4 to 33.1%. CONCLUSION: Percutaneous multiple small-diameter drilling core decompression significantly reduced the lesion volume for AFHN and IFHN, but the effect on SIFHN was not good.

Upregulation of HSP72 attenuates tendon adhesion by regulating fibroblast proliferation and collagen production via blockade of the STAT3 signaling pathway.

The proliferation of fibroblasts creates an environment favoring post-operative tendon adhesion, but targeted therapy of this pathology remains in its infancy. In this study, we explored the effect of heat shock protein 72 (HSP72), a major inducible member of the heat shock protein family that can protect cells against many cellular stresses including heat shock, on fibroblast proliferation in tendon adhesion, with its underlying mechanisms investigated. HSP72 expression was examined in an established rat model of tendon injury using RT-qPCR and immunoblot analysis. After conducting ectopic expression and depletion experiments in fibroblast NIH3T3 cells, we determined the effects of HSP72 on the expression of α-SMA and STAT3 signaling pathway-related genes, fibroblast proliferation, as well as collagen production. The mRNA (65.46%) and protein (63.65%) expression of HSP72 was downregulated in the rat model of tendon injury. The in vitro experiments revealed that overexpression of HSP72 inhibited fibroblast proliferation (42.57%) and collagen production (45.60%), as well as reducing α-SMA expression (42.49%) and the extent of STAT3 phosphorylation (55.46%). Moreover, we observed that HSP72 overexpression reduced inflammation as well as the number of inflammatory cell infiltration and fibroblasts in vivo. Furthermore, the inhibited extent of STAT3 phosphorylation contributed to the impaired fibroblast proliferation and collagen production evoked by upregulated HSP72. In summary, the present study unveils an inhibitory role of HSP72 in tendon adhesion via inactivation of the STAT3 signaling pathway. This finding may enable the development of new therapeutic strategies for the prevention against tendon adhesion.

Egr1/p300/ACE signal mediates postnatal osteopenia in female rat offspring induced by prenatal ethanol exposure.

Prenatal ethanol exposure induces developmental toxicities of multiple organs in offspring. Here, we investigate the effects of prenatal ethanol exposure on bone mass in postnatal offspring and explore its intrauterine programming mechanism. We found that prenatal ethanol exposure could induce bone dysplasia in fetuses and postnatal osteopenia in female offspring, accompanied by the sustained activation of the local renin-angiotensin systems (RAS) and inhibition of bone formation. Additionally, we also found that histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac levels in the promoter region of angiotensin-converting enzyme (ACE) were increased in female offspring exposed to ethanol during pregnancy. In vitro, ethanol suppressed the formation of mineralized nodules and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which was blocked by enalapril. Furthermore, ethanol promoted the expression and nuclear translocation of early growth response factor 1 (Egr1), which participated in the promotion of histone acetylation of ACE and subsequent RAS activation, by recruiting p300 and binding to the ACE promoter region directly. These findings indicate that the sustained activation of the local RAS might participate in bone dysplasia in fetus and postnatal osteopenia in the female offspring, while the Egr1/p300/ACE signal might be a key promoter of the sustained activation of the local RAS of the long bone.

Nicotine exposure during pregnancy programs osteopenia in male offspring rats via α4ß2-nAChR-p300-ACE pathway.

Prenatal nicotine exposure (PNE) induces developmental toxicity in offspring. However, the long-term harmful effects on bone development and the intrauterine programming mechanism attributed to PNE remain unclear. In the present research, pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg/d) to obtain and analyze bone samples from the fetal and adult offspring. Bone marrow mesenchymal stem cells (BMSCs) were treated with nicotine during osteogenic differentiation to clarify the related molecular mechanisms. The results indicated that PNE led to bone dysplasia in the fetuses and reduced bone mass in the adult offspring, which was mediated by the sustained activation of the local bone renin angiotensin system (RAS) and suppressed osteogenic differentiation before and after birth. In vitro, nicotine suppressed BMSCs' osteogenic function through promoting angiotensin-converting enzyme (ACE) expression and activating RAS. Furthermore, nicotine induced histone acetylase p300 into the nuclei of the BMSCs by acting on the α4ß2-nicotinic acetylcholine receptor (α4ß2-nAChR), leading to the increased histone 3 lysine 9 acetylation level of ACE and RAS activation. Taken together, the sustained activation of local bone RAS mediated prenatal nicotine-induced osteopenia in adult offspring via the α4ß2-nAChR-p300-ACE pathway.-Xiao, H., Wen, Y., Pan, Z., Shangguan, Y., Magdalou, J., Wang, H., Chen, L. Nicotine exposure during pregnancy programs osteopenia in male offspring rats via α4ß2-nAChR-p300-ACE pathway.

Activation of local bone RAS by maternal excessive glucocorticoid participated in the fetal programing of adult osteopenia induced by prenatal caffeine exposure.

This study was aimed to investigate whether and how prenatal caffeine exposure (PCE) could induce osteopenia in the adult offspring. Pregnant rats were treated with prenatal caffeine 12 mg/100 g body weight per day from pregnant day 9 to 20, while rat bone marrow mesenchymal stem cells (BMSCs) were treated with exogenous corticosterone during osteogenic induction. Shorter femur and primary ossification center was observed in the PCE offspring, as well as less bone trabecular and poor biomechanical intensity. Local gene expression of glucocorticoid receptor (GR) and angiotensin converting enzyme (ACE), as well as angiotensin 2 content, was found to be stimulated, while the expression of bone gamma-carboxyglutamate protein (BGLAP), alkaline phosphatase (ALP) and bone sialoprotein (BSP) was found to be suppressed, with hypomethylation of ACE promoter. Corticosterone (1250 nM) suppressed osteogenic differentiation of BMSCs and gene expression of BGLAP, ALP and BSP, which was attenuated by enalapril, while it stimulated ACE mRNA expression and induced hypomethylation of ACE promoter, which was attenuated by mifepristone. It indicated that PCE caused bone growth retardation and adult osteopenia in offspring, which might be triggered by the activation of local RAS induced by excessive maternal glucocorticoid, while the hypomethylation of ACE gene might be the key point of the sustained activation of the local RAS.

Intravenous morphine titration vs. oral hydrocodone/acetaminophen for adults with lower extremity displaced fracture in an emergency department setting: A randomized controlled trial.

The objective of the present study was to test the hypothesis that intravenous morphine titration provides superior analgesia to oral hydrocodone/acetaminophen for patients with lower extremity displaced fracture in an emergency department (ED) setting. A prospective, randomized clinical trial of ED patients suffering acute lower extremity displaced fracture pain was performed with a total of 206 participants included. After application of exclusion criteria, the cohort comprised 166 patients, 85 of which were randomly allocated to the oral hydrocodone/acetaminophen (5 mg/500 mg) group and 81 to the intravenous morphine titration (every 5 min by 3-mg increments) group. The main outcome was the visual analogue scale (VAS) at different time-points after the first dose of analgesic was administered. Secondary outcomes included the VAS change during the skeletal traction operation and short-term adverse events. The results demonstrated that the initial VSA of the participants was similar at the baseline on arrival at the ED (P=0.2582). At the time-points of 5, 15, 30 min after the first dose of analgesic administered, the intravenous morphine titration group exhibited a greater VAS reduction compared with that in the oral hydrocodone/acetaminophen group (P<0.01). The differences between the 2 groups were not statistically significant at 1 h or thereafter. The incidence of short-term adverse events was similar between the 2 groups but sedation, whose incidence in the morphine group was markedly increased, may not be arbitrarily attributed to adverse events. It was concluded that, compared with oral hydrocodone/acetaminophen, intravenous morphine titration provided a rapid and sufficient pain relief and equivalent short-term adverse events for patients with lower extremity displaced fracture in an ED setting.

Prenatal nicotine exposure retards osteoclastogenesis and endochondral ossification in fetal long bones in rats.

This study investigated the mechanisms underlying the retarded development of long bone in fetus by prenatal nicotine exposure (PNE) which had been demonstrated by our previous work. Nicotine (2.0 mg/kg.d) or saline was injected subcutaneously into pregnant rats every morning from gestational day (GD) 9 to 20. Fetal femurs or tibias were harvested for analysis on GD 20. We found massive accumulation of hypertrophic chondrocytes and a delayed formation of primary ossification center (POC) in the fetal femur or tibia of rat fetus after PNE, which was accompanied by a decreased amount of osteoclasts in the POC and up-regulated expression of osteoprotegerin (OPG) but by no obvious change in the expression of receptor activator of NF-κB ligand (RANKL). In primary osteoblastic cells, both nicotine (0, 162, 1620, 16,200 ng/ml) and corticosterone (0, 50, 250, 1250 nM) promoted the mRNA expression of OPG but concentration-dependently suppressed that of RANKL. Furthermore, blocking α4ß2-nicotinic acetylcholine receptor (α4ß2-nAChR) or glucocorticoid receptor rescued the above effects of nicotine and corticosterone, respectively. In conclusion, retarded osteoclastogenesis may contribute to delayed endochondral ossification in long bone in fetal rats with PNE. The adverse effects of PNE may be mediated via the direct effect of nicotine and indirect effect of maternal corticosterone on osteoblastic cells.

Increased H3K27ac level of ACE mediates the intergenerational effect of low peak bone mass induced by prenatal dexamethasone exposure in male offspring rats.

Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multiple organs in offspring. Here, we verified the intergenerational effect of low peak bone mass induced by PDE and investigated its intrauterine programming mechanism. Pregnant rats were injected subcutaneously with 0.2 mg/kg/d dexamethasone from gestation day (GD) 9 to 20. Some pregnant rats were killed for the fetuses on GD20, and the rest went on to spontaneous labor to produce the first-generation (F1) offspring. The adult F1 male offspring were mated with normal females to produce the F2 offspring. In vivo, PDE leads to low peak bone mass in F1 male offspring rats at postnatal week (PW) 28. Furthermore, PDE reduced the bone mass in F1 male offspring from GD20 to PW12. Meanwhile, the osteogenic differentiation was suppressed and the local renin-angiotensin system (RAS) was activated continuously by PDE. Moreover, the histone 3 lysine 27 acetylation (H3K27ac) level in angiotensin-converting enzyme (ACE) promoter region was increased by PDE from GD20 to PW12. Likewise, PDE induced the low peak bone mass and the activated local RAS in F2 male offspring. Meaningfully, the H3K27ac level of ACE was increased by PDE in the F2 offspring. In vitro, dexamethasone inhibited bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and promoted RAS activation. Furthermore, dexamethasone recruited CCAAT/enhancer-binding protein α and p300 into the BMSCs nucleus by activating glucocorticoid receptor, which cooperatively increased the H3K27ac level in the ACE promoter region. In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE.

Value of antibiotic prophylaxis in routine knee arthroscopy : A retrospective study.

OBJECTIVE: Prophylactic antibiotic use prior to routine knee arthroscopy remains controversial. It is important to know whether antibiotics help decrease the surgical site infection (SSI) rate. Our aims were to assess the efficacy of antibiotic prophylaxis in preventing SSI and to identify risk factors for SSI following routine knee arthroscopy without an implant. METHODS: A retrospective study was conducted using the electronic medical records at the authors' hospital to identify patients that underwent routine knee arthroscopy without an implant between October 2010 and October 2016. Data on demographics, clinical characteristics and antibiotic administration were extracted. Arthroscopic diagnosis, debridement, partial or complete meniscectomy, arthroscopic shaving and microfracture, removal of loose bodies, synovectomy and lateral retinacular release were included. Complex knee arthroscopy with an implant was excluded. Patients were divided into evaluation (with prophylactic antibiotics) and control (no antibiotic treatment) groups. Continuous variables between groups were compared using the Student's t-test. Data were analyzed using the Chi-squared test for percentages between groups. Multivariate logistic regression was used to identify independent risk factors of SSI. RESULTS: Of 1326 patients, 614 (46.3%) received prophylactic antibiotics, while 712 (53.7%) did not. There were seven (0.53%) SSIs. The SSI rate did not differ significantly between patients receiving antibiotics (0.49%, three) and those not (0.56%, four). Five patients (0.37%) had superficial infections, two (0.33%) were in the prophylactic antibiotic group and three (0.42%) were in the other group. Deep infections occurred in two patients (0.15%), one (0.16%) in the prophylactic antibiotic group and one (0.14%) in the other group. The difference between the two groups was not statistically significant (P = 1.0). Age over 50 years was associated with an increased risk of SSI (relative ratio [RR] = 1.469, 95% confidence interval [CI] 1.09-2.13, P = 0.009). CONCLUSIONS: Prophylactic antibiotic use in routine knee arthroscopy without an implant may not be necessary. Age over 50 years was associated with an increased risk of SSI.