Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis.

Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.

Fast instruments and tissues segmentation of micro-neurosurgical scene using high correlative non-local network.

Surgical scene segmentation provides critical information for guidance in micro-neurosurgery. Segmentation of instruments and critical tissues contributes further to robot assisted surgery and surgical evaluation. However, due to the lack of relevant scene segmentation dataset, scale variation and local similarity, micro-neurosurgical segmentation faces many challenges. To address these issues, a high correlative non-local network (HCNNet), is proposed to aggregate multi-scale feature by optimized non-local mechanism. HCNNet adopts two-branch design to generate features of different scale efficiently, while the two branches share common weights in shallow layers. Several short-term dense concatenate (STDC) modules are combined as the backbone to capture both semantic and spatial information. Besides, a high correlative non-local module (HCNM) is designed to guide the upsampling process of the high-level feature by modeling global context generated from the low-level feature. It filters out confused pixels of different classes in the non-local correlation map. Meanwhile, a large segmentation dataset named NeuroSeg is constructed, which contains 15 types of instruments and 3 types of tissues that appear in meningioma resection surgery. The proposed HCNNet achieves the state-of-the-art performance on NeuroSeg, it reaches an inference speed of 54.85 FPS with the highest accuracy of 59.62% mIoU, 74.7% Dice, 70.55% mAcc and 87.12% aAcc.

Effects of Chinese medicine for COVID-19 rehabilitation: a multicenter observational study.

OBJECTIVES: This study aimed to evaluate the effects of Chinese Medicine (CM) on the health condition of the post-COVID-19 patients, particularly with the CM Syndrome diagnosis and Body Constitutions (BC), as well as related clinical characteristics. METHODS: 150 participants who had COVID-19 and discharged from Hong Kong public hospitals were recruited. They were provided with three to six months of CM treatments, during which assessments were made per month and at follow-up on their CM syndromes, BC, lung functions, and other medical conditions. This study was divided into two parts: (1) Retrospective survey: medical history of participants during COVID-19 hospitalization was collected during the baseline visit; (2) Prospective observation and assessments: clinical symptoms, lung functions, and BC status were evaluated in participants receiving CM treatment based on syndrome differentiation and clinical symptoms. RESULTS: The median hospitalization period was 16 days. Symptoms were presented in 145 (96.6%) patients at the day they were diagnosed with COVID-19. Fever, fatigue, and dry cough were the most common symptoms, exhibiting in 59.3% (89 of 150), 55.3% (83 of 150), and 46% (70 of 150) participants, respectively. Among the 150 post-COVID patients, majority (71.3%) were of the two particular post-COVID CM Syndromes (Qi Deficiency of Lung and Spleen, and Qi and Yin Deficiency). Upon CM treatment, there was an observable increase in participants reaching a balanced BC (i.e. healthy body conditions). The increase was observed to be more prominent in those without the particular CM Syndromes compared to those with the CM Syndromes. Main clinical symptoms in participants with the CM Syndromes decreased upon CM treatment. Occurrence of fatigue also dropped after CM treatment though not all accompanied clinical symptoms were resolved fully. Further to the improvement in terms of CM assessments, lung functions of the participants were found to show improvement after treatment. Both the performance in 6MWT and scores in the LFQ improved upon CM treatments (P < 0.05). CONCLUSION: This study provided evidence for individualized CM treatment on COVID-19 rehabilitation concerning the clinical symptoms improvements, lung functions improvement, and achieving a balanced BC. It is believed that CM may be a key to further promote rehabilitation and resolution of residual symptoms. Long-term large scale follow-up studies on sub-categorising post-COVID patients according to different CM syndromes would be required to further elucidate treatment of persistent symptoms that may be associated with long-COVID.

Inhibition of METTL3 attenuates renal injury and inflammation by alleviating TAB3 m6A modifications via IGF2BP2-dependent mechanisms.

The role of N6-methyladenosine (m6A) modifications in renal diseases is largely unknown. Here, we characterized the role of N6-adenosine-methyltransferase-like 3 (METTL3), whose expression is elevated in renal tubules in different acute kidney injury (AKI) models as well as in human biopsies and cultured tubular epithelial cells (TECs). METTL3 silencing alleviated renal inflammation and programmed cell death in TECs in response to stimulation by tumor necrosis factor-α (TNF-α), cisplatin, and lipopolysaccharide (LPS), whereas METTL3 overexpression had the opposite effects. Conditional knockout of METTL3 from mouse kidneys attenuated cisplatin- and ischemic/reperfusion (I/R)-induced renal dysfunction, injury, and inflammation. Moreover, TAB3 [TGF-ß-activated kinase 1 (MAP3K7) binding protein 3] was identified as a target of METTL3 by m6A methylated RNA immunoprecipitation sequencing and RNA sequencing. The stability of TAB3 was increased through binding of IGF2BP2 (insulin-like growth factor 2 binding protein 2) to its m6A-modified stop codon regions. The proinflammatory effects of TAB3 were then explored both in vitro and in vivo. Adeno-associated virus 9 (AAV9)-mediated METTL3 silencing attenuated renal injury and inflammation in cisplatin- and LPS-induced AKI mouse models. We further identified Cpd-564 as a METTL3 inhibitor that had better protective effects against cisplatin- and ischemia/reperfusion-induced renal injury and inflammation than S-adenosyl-l-homocysteine, a previously identified METTL3 inhibitor. Collectively, METTL3 promoted m6A modifications of TAB3 and enhanced its stability via IGF2BP2-dependent mechanisms. Both genetic and pharmacological inhibition of METTL3 attenuated renal injury and inflammation, suggesting that the METTL3/TAB3 axis is a potential target for treatment of AKI.

Guideline Acupuncture for low back pain: a clinical practice guideline from the Hong Kong taskforce of standardized acupuncture practice.

OBJECTIVE: To develop a clinical practice guideline to guide the treatment of low back pain by acupuncture. METHODS: An integrative approach of systematic review of literature, clinical evidence classification, expert opinion surveying, and consensus establishing via a Delphi program was utilized during the developing process. Both evidence-based practice standards and the personalized features of acupuncture were taken into considerations. RESULTS: Based on clinical evidence and expert opinions, we developed a clinical practice guideline for the treatment of low back pain with acupuncture. These recommendations have a wide coverage spanning from Western Medicine diagnosis and Traditional Chinese Medicine syndrome differentiation, to acupuncture treatment procedures, as well as post treatment care for rehabilitation and follow-ups. The recommendations for acupuncture practice included treatment principles, therapeutic regimens, and operational procedures. The levels of evidence and strength of recommendation were rated for each procedure of practice. CONCLUSION: A clinical practice guideline for acupuncture treating low back pain was developed based on contemporary clinical evidence and experts' consensus to provide best currently agreeable practice guideline for domestic and international stakeholders.

Epigenetics and Inflammation in Diabetic Nephropathy.

Diabetic nephropathy (DN) leads to high morbidity and disability. Inflammation plays a critical role in the pathogenesis of DN, which involves renal cells and immune cells, the microenvironment, as well as extrinsic factors, such as hyperglycemia, chemokines, cytokines, and growth factors. Epigenetic modifications usually regulate gene expression via DNA methylation, histone modification, and non-coding RNAs without altering the DNA sequence. During the past years, numerous studies have been published to reveal the mechanisms of epigenetic modifications that regulate inflammation in DN. This review aimed to summarize the latest evidence on the interplay of epigenetics and inflammation in DN, and highlight the potential targets for treatment and diagnosis of DN.

Edible and Herbal Plants for the Prevention and Management of COVID-19.

Background: The outbreak of the pandemic coronavirus disease 2019 (COVID-19) has now become a global pandemic spreading throughout the world. Unfortunately, due to the high infectiousness of the novel ß-coronavirus, it is very likely to become an ordinary epidemic. The development of dietary supplements and functional foods might provide a strategy for the prevention and management of COVID-19. Scope and Approach: A great diversity of potential edible and medicinal plants and/or natural compounds showed potential benefits in managing SARS, which may also combat COVID-19. Moreover, many plants and compounds have currently been proposed to be protective against COVID-19. This information is based on data-driven approaches and computational chemical biology techniques. In this study, we review promising candidates of edible and medicinal plants for the prevention and management of COVID-19. We primarily focus on analyzing their underlying mechanisms. We aim to identify dietary supplements and functional foods that assist in managing this epidemic. Key findings and Conclusion: We infer that acetoside, glyasperin, isorhamnetin, and several flavonoid compounds may prevent and/or be effective in managing COVID-19 by targeting the viral infection, reducing the host cytokine storm, regulating the immune response, and providing organ protection. These bioactive dietary components (used either alone or in combination) might assist in the development of dietary supplements or functional foods for managing COVID-19.

Effect of Herbs on Postoperative Intestinal Obstruction: A Case Report.

Postoperative intestinal obstruction is one of the most common and challenging complications after patients receive pelvic or abdominal surgery. The effectiveness of conventional therapies is varied and they are associated with a high recurrence rate. Traditional Chinese Medicine can be beneficial in the treatment of intestinal obstruction. In this case, a 65-year-old woman had progressively increasing abdominal pain, distension, and constipation following total hip replacement surgery. The patient was diagnosed with partial intestinal obstruction and was treated for 6 days without success using conventional Western medicine, including Enema Glycerini and Sodium Phosphates Rectal Solution. We received a request from the surgical department for a Chinese medicine consultation. Two doses of modified Dachengqi Decoction herbal formula were prescribed for the patient. The patient had her first flatus and defecation within 2 hours after ingestion of the first dose of herbal medicine and subsequently all of the symptoms were relieved. The patient was soon discharged without any further complications; a 5-year follow-up indicated that the patient had no recurrence of intestinal obstruction. This case is the first to report the effect of a Chinese herbal decoction in achieving remission of intestinal obstruction with only 1 dose. Large scale randomized controlled trials are warranted to confirm our findings.

DNA methylation of FTO promotes renal inflammation by enhancing m6A of PPAR-α in alcohol-induced kidney injury.

Alcohol consumption is one of the risk factors for kidney injury. The underlying mechanism of alcohol-induced kidney injury remains largely unknown. We previously found that the kidney in a mouse model of alcoholic kidney injury had severe inflammation. In this study, we found that the administration of alcohol was associated with the activation of NLRP3 inflammasomes and NF-κB signaling, and the production of pro-inflammatory cytokines. Whole-genome methylation sequencing (WGBS) showed that the DNA encoding fat mass and obesity-associated protein (FTO) was significantly methylated in the alcoholic kidney. This finding was confirmed with the bisulfite sequencing (BSP), which showed that alcohol increased DNA methylation of FTO in the kidney. Furthermore, inhibition of DNA methyltransferases (DNMTs) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified peroxisome proliferator activated receptor-α (PPAR-α) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-α m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-κB-driven renal inflammation in the kidney. These findings may provide novel strategies for preventing and treating alcoholic kidney diseases.

7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation.

BACKGROUND: 7-Hydroxycoumarin (7-HC), also known as umbelliferon, is commonly found in Chinese herbs (e.g. Eucommiae Cortex, Prunellae Spica, Radix Angelicae Biseratae). Previous laboratory studies have indicated that 7-HC has anti-inflammatory, anti-oxidative, and anti-tumor effects. Cisplatin is a widely used chemotherapeutic agent for cancer. Nephrotoxicity is one of the limiting side effects of cisplatin use. PURPOSE: This study aimed to evaluate the renoprotective effect of 7-HC in a cisplatin-induced acute kidney injury (AKI) mouse model. METHODS: AKI was induced in male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin at 20 mg/kg. The mice received 7-HC at 30, 60, and 90 mg/kg intraperitoneally before or after cisplatin administration. Renal function, necroptosis, and cell proliferation were measured. Mechanisms underlying the reno-protective effect of 7-HC were explored in renal tubular epithelial cells treated with or without cisplatin. RESULTS: In-vivo experiments showed that 7-HC significantly improved the loss in kidney function induced by cisplatin, as indicated by lower levels of serum creatinine and blood urea nitrogen, in AKI mice. Consistent herewith, cisplatin-induced tubular damage was alleviated by 7-HC as shown by morphological (periodic acid-Schiff staining) and kidney injury marker (KIM-1) analyses. We found that 7-HC suppressed renal necroptosis via the RIPK1/RIPK3/MLKL pathway and accelerated renal repair as evidenced by the upregulation of cyclin D1 in cisplatin-induced nephropathy. In-vitro experiments showed that knockdown of Sox9 attenuated the suppressive effect of 7-HC on KIM-1 and reversed the stimulatory effect of 7-HC on cyclin D1 expression in cisplatin-treated HK-2 cells, indicating that 7-HC may protect against AKI via a Sox9-dependent mechanism. CONCLUSION: 7-HC inhibits cisplatin-induced AKI by suppressing RIPK1/RIPK3/MLKL-mediated necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. 7-HC may serve as a preventive and therapeutic agent for AKI.

Smad3 promotes AKI sensitivity in diabetic mice via interaction with p53 and induction of NOX4-dependent ROS production.

The incidence and severity of acute kidney injury (AKI) is increased yearly in diabetic patients. Although the mechanisms for this remain unclear, the prevention of AKI in diabetic nephropathy is feasible and of value. As we detected highly activation of TGF-ß/Smad3 signaling in both human biopsy and mouse model of diabetic nephropathy, we hypothesized that Smad3 activation in diabetic kidneys may increase AKI sensitivity. We tested our hypothesis in vitro using TGF-ß type II receptor (TGF-ßRII) disrupted tubular epithelial cells (TECs) and in vivo in mice with streptozotocin (STZ)-induced diabetic nephropathy before the induction of ischemia/reperfusion (I/R) injury. We found that high glucose (HG)-cultured TECs showed increased inflammation, apoptosis and oxidative stress following hypoxia/reoxygenation (H/R) injury. Disruption of TGF-ßRII attenuated cell injury induced by H/R in HG-treated TECs. Consistently, Smad3 knockdown in diabetic kidney attenuated I/R-induced AKI. Mechanistically, Smad3 binds to p53 and enhances p53 activity in cells treated with HG and H/R, which may lead to TECs apoptosis. Additionally, ChIP assay showed that Smad3 bound with the promoter region of NOX4 and induced ROS production and inflammation. In conclusion, our results demonstrate that Smad3 promotes AKI susceptibility in diabetic mice by interacting with p53 and NOX4.

Alcohol promotes renal fibrosis by activating Nox2/4-mediated DNA methylation of Smad7.

Alcohol consumption causes renal injury and compromises kidney function. The underlying mechanism of the alcoholic kidney disease remains largely unknown. In the present study, an alcoholic renal fibrosis animal model was first employed which mice received liquid diet containing alcohol for 4 to 12 weeks. The Masson's Trichrome staining analysis showed that kidney fibrosis increased at week 8 and 12 in the animal model that was further confirmed by albumin assay, Western blot, immunostaining and real-time PCR of fibrotic indexes (collagen I and α-SMA). In vitro analysis also confirmed that alcohol significantly induced fibrotic response (collagen I and α-SMA) in HK2 tubular epithelial cells. Importantly, both in vivo and in vitro studies showed alcohol treatments decreased Smad7 and activated Smad3. We further determined how the alcohol affected the balance of Smad7 (inhibitory Smad) and Smad3 (regulatory Smad). Genome-wide methylation sequencing showed an increased DNA methylation of many genes and bisulfite sequencing analysis showed an increased DNA methylation of Smad7 after alcohol ingestion. We also found DNA methylation of Smad7 was mediated by DNMT1 in ethyl alcohol (EtOH)-treated HK2 cells. Knockdown of Nox2 or Nox4 decreased DNMT1 and rebalanced Smad7/Smad3 axis, and thereby relieved EtOH-induced fibrotic response. The inhibition of reactive oxygen species by the intraperitoneal injection of apocynin attenuated renal fibrosis and restored renal function in the alcoholic mice. Collectively, we established novel in vivo and in vitro alcoholic kidney fibrosis models and found that alcohol induces renal fibrosis by activating oxidative stress-induced DNA methylation of Smad7. Suppression of Nox-mediated oxidative stress may be a potential therapy for long-term alcohol abuse-induced kidney fibrosis.

Self-administered acupressure for knee osteoarthritis in middle-aged and older adults: a pilot randomized controlled trial.

OBJECTIVE: To test the acceptability and feasibility of self-administered acupressure as an intervention for knee pain among middle-aged and older adults with knee osteoarthritis (KOA). METHODS: In this pilot randomized controlled trial, 35 participants with KOA were randomized to receive self-administered acupressure (n = 17, two self-administered acupressure training sessions followed by self-practice for 6 weeks) or knee health education (n = 18, two health education sessions about KOA management followed by self-care for 6 weeks). Current pain intensity (primary outcome) was measured using a Numeric Rating Scale (NRS) at baseline and weeks 1, 2, 4 and 6 (post-intervention). Secondary outcome measures included worst and least pain intensity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM) of the knee joints and Short-Form Six-Dimension (SF-6D) scores for health-related quality of life. RESULTS: Participants in both groups attended all training sessions. In the self-administered acupressure group, all subjects mastered the acupressure technique and passed a consistency check. Both groups showed a decreasing trend in current knee pain intensity measured using NRS post-intervention. A medium between-group effect size (0.40) was found, but between-group differences were not statistically significant. The other secondary outcome measures were also comparable between both groups post-intervention (all p > 0.05). CONCLUSION: A two-session self-administered acupressure training was acceptable to and feasible in participants with KOA. The data generated allowed for calculation of a sample size for a definitive randomized controlled trial (RCT) to confirm whether self-acupressure is effective for pain management in KOA. Furthermore trials with adequate power and longer follow-up periods are warranted.

Acupuncture for overactive bladder in adults: a systematic review and meta-analysis.

BACKGROUND: Overactive bladder is prevalent in adults over 40 years of age and its prevalence increases with age. The use of acupuncture in adults with overactive bladder is increasing globally. However, its effectiveness/efficacy and safety have not yet been confirmed. OBJECTIVE: To determine the effectiveness/efficacy and safety of acupuncture and to identify the pattern of commonly used traditional acupuncture points in the management of overactive bladder in adults. METHODS: Ten electronic English and Chinese language databases were systematically searched and two English together with four Chinese journals relevant to acupuncture were manually searched in libraries for randomised controlled trials (RCTs) of acupuncture for overactive bladder in adults from their inception to March 2017. The Cochrane risk of bias tool was used to assess the methodological quality of the RCTs. RevMan v.5.3 software was employed for data analysis. RESULTS: Seven eligible trials involving 695 participants were included. Meta-analysis showed that acupuncture was comparable to drugs (tolterodine tartrate/solifenacin) in the reduction of micturition episodes over 24 hours (pooled standardised mean difference (SMD) 0.36, 95% CI -0.23 to 0.95; I2=83%), increase in voided volume of each micturition episode (pooled SMD -0.15, 95% CI -0.36 to 0.05; I2=0%), and reduction of overactive bladder symptom score (pooled SMD -0.23, 95% CI -1.30 to 0.85; I2=91%). In addition, acupuncture was not significantly different compared with placebo in the reduction of overactive bladder symptom score (pooled SMD -2.36, 95% CI -5.64 to 0.93; I2=97%). No serious adverse events were reported. CONCLUSIONS: No significant differences in effectiveness or efficacy were found between acupuncture and drug or between verum and sham acupuncture, respectively. Further high-quality studies are required.

Petchiether A attenuates obstructive nephropathy by suppressing TGF-ß/Smad3 and NF-κB signalling.

Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor-ß1 (TGF-ß1)/Smad3-driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small-molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF-ß1-induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin-1ß and tumour necrosis factor-α) and reducing extracellular matrix deposition (α-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down-regulated the expression of the fibrotic marker collagen I in TGF-ß1-treated renal epithelial cells. Further, we found that petA dose-dependently suppressed Smad3-responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF-ß/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF-ß/Smad3 signalling.

Dendrobine targeting JNK stress signaling to sensitize chemotoxicity of cisplatin against non-small cell lung cancer cells in vitro and in vivo.

BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide. Cisplatin-based chemotherapy is the standard treatment for lung cancer, but chemoresistance and adverse effects especially cardiotoxicity limit its efficacy. PURPOSE: The efficacy of combination treatment of dendrobine, a plant alkaloid isolated from Dendrobium nobile, with cisplatin was examined as a possible anti-non-small cell lung cancer strategy. METHODS: The cytotoxicity of dendrobine and cisplatin against A549 lung cancer cells was analyzed by MTT and colony formation assays. Apoptosis was measured by annexin V/PI double staining. Apoptosis-related proteins were assessed by western blotting and qPCR analysis. In vivo efficacy was determined using A549 xenograft in nude mice. JNK and Bim inhibition were achieved by siRNA knockdown and/or chemical inhibition. Cardiotoxicity was assessed by serum creatine phosphokinase activity assay. RESULTS: Dendrobine induced apoptotic cell death through mitochondrial-mediated pathway. Combination treatment of dendrobine with cisplatin showed enhanced cytotoxicity through stimulation of JNK/p38 stress signaling pathways and, consequently, the induction of apoptosis involving pro-apoptotic proteins Bax and Bim. In addition, dendrobine attenuated the body weight reduction and cardiotoxicity induced by cisplatin in nude mice. CONCLUSION: The combination treatment showed enhanced anticancer activity toward non-small cell lung cancer cells without aggravating the cardiotoxic effects of cisplatin suggesting that the combination strategy deserves further investigation for human lung cancer treatment.

Analgesic Effect of Sinew Acupuncture for Patients with Soft-Tissue Injuries: A Pilot Trial.

OBJECTIVE: To investigate the immediate analgesic effect of sinew acupuncture for patients with soft-tissue injuries (STIs). METHODS: Two hundreds eligible adult patients suffering from STIs were recruited and received sinew acupuncture with flexible treatment schedules. The number of treatment sessions was pragmatically decided by each patient on the basis of their pain relief. The outcome measurement was the change of pain rating in the Visual Analogue Scale (VAS) during the first 5 sessions. The adverse effect was also observed. RESULTS: Of the 200 patients recruited, 7 were excluded due to incomplete data. In total, 888 sinew acupuncture treatments were administered to patients at 14 injury sites (including head, neck, shoulder, arm, chest, elbow, wrist, hand, waist and hip, knee, thigh, calf, ankle, and foot) where pain was felt. Compared with the baseline, the VAS rating after the first and last treatments were both significantly reduced at all the injury sites (P<0.01). The VAS rating was also significantly reduced after each session of treatment in the first five sessions (P<0.01). No serious adverse effect was observed. CONCLUSION: Sinew acupuncture had not only an immediate analgesic effect for STIs, but also an accumulated analgesic effect during the first 5 treatment sessions.

Effect of Essential Oil on Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of essential oil treatment for type III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A randomized controlled trial was conducted from December 2014 to October 2015. Seventy type III CP/CPPS patients were assigned to the essential oil group (35 cases) or almond placebo oil control group (35 cases) by a random number table. The oil was smeared by self-massage on the suprapubic and sacral region once a day for 4 weeks. The National Institutes of Health Chronic Prostatitis Syndrome Index (NIH-CPSI) and expressed prostatic secretions (EPS) were examined. The primary outcome was NIH-CPSI pain domain. The secondary outcomes included other NIH-CPSI domains and laboratory examinations of EPS. Adverse events were also observed. RESULTS: Sixty-six subjects completed the full 4-week treatment. There was no significant difference between almond oil control and essential oil groups in terms of the total score of NIH-CPSI, pain, quality of life and urination domain scores of NIH-CPSI and EPS examinations (P>0.05). In the essential oil group, pain between rectum and testicles (perineum) in the domain of pain or discomfort was significantly reduced at week 2 and week 4 compared with almond oil control group (P<0.01). No serious adverse events occurred. CONCLUSION: The essential oil may reduce the pain or discomfort in the perineum region in patients with CP/CPPS. (Registration No. ChiCTR-IPR-14005448).

Silencing of microRNA-375 affects immune function in mice with liver failure by upregulating astrocyte elevated gene-1 through reducing apoptosis of Kupffer cells.

This study aims to investigate how microRNA-375 (miR-375) improves immune function by regulating liver macrophages (Kupffer cells) in mice with liver failure. Forty mice were divided into ConA-1h, ConA-3h, ConA-6h, and control groups, with 10 mice in each group. Mice models of liver failure were established by injecting concanavalin A (ConA) solution via the tail veins of mice, and then primary Kupffer cells were isolated and cultured. Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay were conducted to examine the expressions of miR-375, astrocyte elevated gene-1 (AEG-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1ß in Kupffer cells of mice with liver failure as well as after silencing of miR-375. Flow cytometry was used to determine cell apoptosis. During the liver failure process, miR-375, IL-6, TNF-α, and IL-1ß expressions were increased over time, while AEG-1 expression decreased over time in the control, ConA-1h, ConA-3h, and ConA-6h groups. Opposite alternations were observed after silencing of miR-375. Dual-luciferase reporter gene assay showed that AEG-1 was a target gene of miR-375. Flow cytometry determination showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR-375. Overexpression of AEG-1 could rescue the suppression of IL-6, TNF-α, and IL-1ß expressions in Kupffer cells after the short-term induction of ConA and further inhibit cell apoptosis. Our study provides evidence that miR-375 could regulate Kupffer cells to improve immune function in mice with liver failure.