Role of miRNAs in glucose metabolism of mouse cumulus cells†.

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.

Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes.

In brief: Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos. Abstract: Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Role and action mechanisms of tPA in CRH-induced apoptosis of mouse oviductal epithelial and mural granulosa cells.

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

The molecular mechanism of METTL3 promoting the malignant progression of lung cancer.

Lung cancer remains one of the major causes of cancer-related death globally. Recent studies have shown that aberrant m6A levels caused by METTL3 are involved in the malignant progression of various tumors, including lung cancer. The m6A modification, the most abundant RNA chemical modification, regulates RNA stabilization, splicing, translation, decay, and nuclear export. The methyltransferase complex plays a key role in the occurrence and development of many tumors by installing m6A modification. In this complex, METTL3 is the first identified methyltransferase, which is also the major catalytic enzyme. Recent findings have revealed that METTL3 is remarkably associated with different aspects of lung cancer progression, influencing the prognosis of patients. In this review, we will focus on the underlying mechanism of METT3 in lung cancer and predict the future work and potential clinical application of targeting METTL3 for lung cancer therapy.

Comparison of the BOPPPS model and traditional instructional approaches in thoracic surgery education.

BACKGROUND: BOPPPS (bridge-in, learning objective, pretest, participatory learning, posttest, and summary) is a student-centered modular teaching model that improves classroom teaching effectiveness. This study's primary aim was to explore whether the BOPPPS model has advantages over traditional instructional approaches in teaching lung cancer courses to clinical medical interns. METHODS: A total of 88 students majoring in clinical medicine of Shandong First Medical University and Shandong University, who had clinical practice in thoracic surgery from January 2018 to December 2019, were divided into two groups, receiving the same lung cancer teaching content. The experimental group (n = 44) utilized the BOPPPS model, while the control group (n = 44) used the traditional instructional approach. A questionnaire was used to attain the students' satisfaction and self-evaluation of the course, and a post-study examination was used to assess end-of-course performance. RESULTS: The experimental group's theoretical examination scores with the BOPPPS teaching model were significantly higher than those in the control group. Students preferred the BOPPPS model more than the traditional instructional approach in course satisfaction, student-teacher interaction, learning initiative, analytical ability, clinical thinking ability, and self-study ability (p < 0.05). CONCLUSIONS: Compared with the traditional instructional approach. The BOPPPS model can better inspire clinical medical students' enthusiasm for thoracic surgery and enhance the students' comprehensive ability. In a word, the BOPPPS model has better teaching effectiveness in the clinical teaching practice of thoracic surgery, which is worthy of reference and popularization.

Artemisinin and its derivatives: a potential therapeutic approach for oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common T-cell-mediated oral mucosal disease, whose pathogenesis mainly includes antigen-specific and non-specific mechanisms. As a refractory chronic inflammatory disease, there is still no curable management for OLP till now. FINDINGS: Artemisinins are a family of compounds that are widely used as frontline treatment for malaria worldwide. In addition to its well-established antimalarial properties, emerging evidence hints that artemisinin family drugs also possess preferential immunoregulatory and anti-inflammation properties, such as modifying T lymphocytes' activation and cytokines release, modulating Th1/Th2 balance, activating regulatory T cells (Tregs), modulating inflammatory signaling pathways, as well as acting on non-specific mechanisms of OLP. However, there is still no report focused on the influence of artemisinins on OLP. CONCLUSION: This review outlined the data-based immunomodulatory effects of artemisinins on different immune cells in conjunction with their therapeutic prospective with regard to the pathogenesis of OLP, suggesting that artemisinin and its derivatives might be possible candidates for treatment of OLP.

Role and action mechanisms of miR-149 and miR-31 in regulating function of pig cumulus cells and oocytes.

Understanding the mechanisms for oocyte maturation and optimizing the protocols for in vitro maturation (IVM) are greatly important for improving developmental potential of IVM oocytes. The miRNAs expressed in cumulus cells (CCs) play important roles in oocyte maturation and may be used as markers for selection of competent oocytes/embryos. Although a recent study from our group identified several new CCs-expressed miRNAs that regulate cumulus expansion (CE) and CC apoptosis (CCA) in mouse oocytes, validation of these findings and further investigation of mechanisms of action in other model species was essential before wider applications. By using both in vitro and in vivo pig oocyte models with significant differences in CE, CCA and developmental potential, the present study validated that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes. We demonstrated that miR-149 and miR-31 targeted SMAD family member 6 (SMAD6) and transforming growth factor ß2 (TGFB2), respectively, in the transforming growth factor-ß (TGF-ß) signaling. Furthermore, both miR-149 and miR-31 increased CE and decreased CCA via activating SMAD family member 2 (SMAD2) and increasing the expression of SMAD2 and SMAD family member 4. In conclusion, the present results show that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes by activating the TGF-ß signaling, suggesting that they might be used as markers for pig oocyte quality.

Clinicopathological Significance of STAT3 and p-STAT3 among 91 Patients with Adenocarcinoma of the Esophagogastric Junction.

Adenocarcinoma of the esophagogastric junction (AEG) has increased rapidly worldwide during the last few decades. The purpose of this study is to investigate the clinical and prognostic characteristics of signal transduction and activator of transcription factor 3(STAT3) and phosphorylated STAT3 (p-STAT3) expression in AEG patients. We retrospectively analyzed the immunohistochemical results of 61 AEG patients and followed up for 5 years, while Western blot was performed on tissues from another 30 AEG patients. The results showed that STAT3 and p-STAT3 were overexpressed in AEG tissues (P < 0.05, P < 0.01). The high expression of STAT3 was significantly associated with the pTNM stage (P < 0.05), and the increased expression of p-STAT3 was significantly associated with depth of invasion (pT), lymph node metastasis (pN), and pTNM stage (P < 0.05, P < 0.05, P < 0.05). The 5-year survival rate for AEG patients was 41.0% and was significantly associated with tumor differentiation, pN, pTNM, and p-STAT3 (P < 0.05, P < 0.01, P < 0.05, P < 0.01). Cox regression analysis confirmed that tumor differentiation, pN, and high expression of p-STAT3 were independent risk factors for the 5-year survival rate in patients with AEG (P < 0.05, P < 0.01, P < 0.05). Our study showed that STAT3 and p-STAT3 play a critical role in AEG development.

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review).

Esophageal cancer (EC) is the seventh most common cancer globally, and the overall 5­year survival rate is only 20%. Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in EC, and its activation is associated with a poor prognosis. STAT3 can be activated by canonical pathways such as the JAK/STAT3 pathway as well as non­canonical pathways including the Wnt/STAT3 and COX2/PGE2/STAT3 pathways. Activated STAT3, present as phosphorylated STAT3 (p­STAT3), can be transported into the nucleus to regulate downstream genes, including VEGF, cyclin D1, Bcl­xL, and matrix metalloproteinases (MMPs), to promote cancer cell proliferation and induce resistance to therapy. Non­coding RNAs, including microRNAs (miRNAs/miRs), circular RNAs (circRNAs), and long non­coding RNAs (lncRNAs), play a vital role in regulating the STAT3 signaling pathway in EC. Several miRNAs promote or suppress the function of STAT3 in EC, while lncRNAs and circRNAs primarily promote the effects of STAT3 and the progression of cancer. Additionally, various drugs and natural compounds can target STAT3 to suppress the malignant behavior of EC cells, providing novel insights into potential EC therapies.

[Jiao's scalp acupuncture combined with virtual reality rehabilitation training for motor dysfunction in patients with Parkinson's disease: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between Jiao's scalp acupuncture combined with virtual reality (VR) rehabilitation training and VR rehabilitation training alone for motor dysfunction in patients with Parkinson's disease (PD). METHODS: A total of 52 patients with PD were randomly divided into an observation group and a control group, 26 cases in each group. The patients in both groups were treated with routine basic treatment, and the patients in the control group were treated with VR rehabilitation training. The patients in the observation group were treated with Jiao's scalp acupuncture on the basis of the control group. The scalp points included the movement area, balance area and dance tremor control area. Both groups were treated once a day, 5 times a week for a total of 8 weeks. Before treatment and 4 and 8 weeks into treatment, the gait parameters (step distance, step width, step speed and step frequency), timed "up and go" test (TUGT) time and unified Parkinson's disease rating scale part Ⅲ (UPDRS-Ⅲ) score were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Four weeks into treatment, except for the step width in the control group, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01, P<0.05); the step distance in the observation group was better than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05). Eight weeks into treatment, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01); the step distance and step speed in the observation group were better than those in the control group, the TUGT time in the observation group was shorter than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05, P<0.01). The total effective rate was 92.3% (24/26) in the observation group, which was higher than 69.2% (18/26) in the control group (P<0.05). CONCLUSION: Jiao's scalp acupuncture combined with VR rehabilitation training could improve the gait parameters, walking ability and motor function in patients with PD. The clinical effect is better than VR rehabilitation training alone.

[Advances about perineuronal nets in the repair of nerve function after spinal cord injury].

Perineuronal nets (PNNs) is a complex network composed of highly condensed extracellular matrix molecules surrounding neurons. It plays an important role in maintaining the performance of neurons and protecting them from harmful substances. However, after spinal cord injury, PNNs forms a physical barrier that surrounds the neuron and limits neuroplasticity, impedes axonal regeneration and myelin formation, and promotes local neuroinflammatory uptake. This paper mainly describes the composition and function of PNNs of neurons and its regulatory effects on axonal regeneration, myelin formation and neuroinflammation after spinal cord injury.

Interferon-γ activated T-cell IRGM-autophagy axis in oral lichen planus.

Oral lichen planus (OLP) is an inflammatory immune disease featured by dense T-cell infiltrate and basal keratinocytes degeneration. Immunity related GTPase M (IRGM) is vital for the induction of autophagy. Our previous studies have demonstrated aberrant autophagy in OLP, however, the involvement of IRGM-autophagy axis in OLP has not yet been revealed. The expression of IRGM and autophagy activity were evaluated in oral mucosal tissues and peripheral T cells of OLP patients and healthy controls, respectively. We found significant upregulation of IRGM and LC3B in lesions of patients with OLP as compared with healthy donors. IRGM, LC3B and NOD2 levels were also elevated in the peripheral T cells of OLP. Then, knockdown of IRGM after electrotransfection with siRNA resulted in attenuated autophagy, growth inhibition, and apoptosis of T cells. In addition, preincubation with IFN-γ promoted the expression of IRGM mRNA and induced autophagy in T cells. Furthermore, IFN-γ decreased the proliferation and apoptosis of T cells, whereas facilitated the viability of keratinocytes in a co-culture system of activated T cells and keratinocytes. Taken together, activated IRGM-autophagy axis under IFN-γ regulation in T cells might participate in the immunoregulatory mechanism of OLP.

Krüppel-Like Factor 6 Splice Variant 1: An Oncogenic Transcription Factor Involved in the Progression of Multiple Malignant Tumors.

Krüppel-like factor 6 (KLF6) is one of the most studied members of the specificity protein/Krüppel-like factor (SP/KLF) transcription factor family. It has a typical zinc finger structure and plays a pivotal role in regulating the biological processes of cells. Recently, it has been considered to play a role in combatting cancer. Krüppel-like factor 6 splice variant 1 (KLF6-SV1), being one of the alternative KLF6 splicing isoforms, participates in tumor occurrence and development and has the potential to become a new target for molecular targeted therapy, although its action mechanism remains to be determined. The purpose of this article is to provide a comprehensive and systematic review of the important role of KLF6-SV1 in human malignant tumors to provide novel insights for oncotherapy.

[Development and analysis of clinical prediction model of acupuncture and moxibustion treatment for stroke at recovery stage].

OBJECTIVE: To develop the clinical prediction model of therapeutic effect in treatment with acupuncture and moxibustion for the patients with stroke at recovery stage under different conditions so as to provide a tool for predicting the therapeutic effect of acupuncture and moxibustion. METHODS: A total of 1410 patients with stroke at recovery stage were collected from the Third Affiliated Hospital of Zhejiang Chinese Medical University from 2012 to 2019. The relevant data were extracted, i.e. sex, age, time of onset, neurological functional deficit score (NFDS) and acupuncture and moxibustion therapy. The difference of NFDS before and after treatment was adopted to evaluate the therapeutic effect in the patients. Using SPSS26.0 software and CART decision tree analysis, the clinical prediction model was developed. RESULTS: The key variables in the prediction model of therapeutic effect in the patients with stroke at recovery stage under different conditions included age, time of onset, hypertension, cardiac disease, diabetes, TCM diagnosis, hemoglobin (HB), serum homocysteine (HCY) and acupuncture and moxibustion therapy. There were 12 main rules generated by the decision tree model, including 8 rules for predicting the improvements of therapeutic effect and 4 rules for predicting the absence of improvements (i.e. no change and deterioration). The accuracy rates of the model training set and test set were 80.0% and 72.8% respectively, the area under curve (AUC) of ROC was 0.797 and the model identification and classification results were satisfactory. CONCLUSION: The clinical prediction model developed by CART decision tree analysis is high in accuracy for the prediction of the therapeutic effect in the patients with stroke at recovery stage under different conditions. Based on the therapeutic effect predicted in the hospital visit, the physicians may adopt the corresponding regimens of acupuncture and moxibustion therapy in patients.

Roles of N6-Methyladenosine Demethylase FTO in Malignant Tumors Progression.

In 2007, the fat mass and obesity-associated (FTO) gene was discovered initially to regulate body mass index and obesity and was subsequently found to be the first mRNA N6-methyladenosine (m6A) demethylation enzyme, which can demethylate m6A. A growing body of evidence shows that m6A modification is involved in a variety of cell biological processes, including cell proliferation, apoptosis, and self-renewal through different regulatory mechanisms. In recent years, a large number of studies have found that m6A modification play key role in the occurrence and development of tumors, such as acute myeloid leukemia, breast cancer, lung cancer, etc. As a function of m6A demethylase, FTO has attracted more and more attention in cancer. There is evidence that specific FTO single nucleotide polymorphisms (SNPs) may be significantly associated with overweight and cancer susceptibility by regulating the expression of related genes. Besides, when the expression level of FTO is altered or dysfunctional, it may be involved in the occurrence and progression of a variety of tumors as a tumor suppressor gene or oncogene, usually in an m6A-dependent manner. Further research found that FTO is involved in the development of different kinds of malignant tumors, but the mechanism is unknown. According to this review, The FTO gene's research progress in tumors is reviewed, aiming to find new targets for molecular pathological diagnosis and molecular targeted therapy of tumors.

[Ethics review characteristics of clinical research of acupuncture and moxibustion].

The elements of ethical review related to clinical research of acupuncture and moxibustion is discussed to provide ideas for various institutions to carry out relevant ethical review. It is believed that the ethical review of clinical research of acupuncture and moxibustion needs to focus on the specificity of acupuncture and moxibustion. Starting from the basic theory of traditional Chinese medicine, the theory of meridians and acupoints and the theory of syndrome differentiation along meridians, the key contents of ethical review such as intervention methods, grouping design and placebo control should be considered, so as to standardize the clinical research of acupuncture and moxibustion and protect the health and rights and interests of participants.

[Effect of electroacupuncture at "Jiaji" (EX-B 2) points on the proliferation and differentiation of oligodendrocyte precursor cells in rats with acute spinal cord injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Jiaji" (EX-B 2) points on the proliferation and differentiation of oligodendrocyte precursor cells in rats with acute incomplete spinal cord injury, and to explore the mechanism of EA on improving motor function of spinal cord injury. METHODS: A total of 72 male SPF SD rats were randomly divided into a sham operation group, a model group, an EA group and a medication group, 18 rats in each group. Each group was further divided into 1-day subgroup, 7-day subgroup and 14-day subgroup, 6 rats in each subgroup. The T10 acute incomplete spinal cord injury model was established by modified Allen's method in the model group, EA group and medication group. The rats in each group received intraperitoneal injection of 5-bromodeoxyuridine (BrdU, 50 mg/kg), once a day, and each subgroup received continuous injection for 1, 7, 14 times for cell proliferation labeling. The rats in the EA group were treated with EA at "Jiaji" (EX-B 2) points 3-4 mm next the spinous process of the upper and lower segments of the injured spinal cord (T9, T11) with a frequency of 2 Hz/100 Hz and intensity of 1-2 mA. The muscle twitch at the treatment site was taken as the degree. The treatment was given 20 min each time, once a day. In the medication group, monosialogangliosides (GM1) was injected intraperitoneally (10 mg/kg), once a day. The subgroups of EA group and medication group were treated for 1, 7, 14 times. The score of Basso Beattie Bresnahan (BBB) was used to evaluate the motor function of hind limbs. The co-expression of BrdU/NG2 positive cells was detected by immunofluorescence, and the expression of Olig2 and Sox10 was detected by Western blot. RESULTS: Compared with the sham operation group, the BBB score was decreased 1 day, 7 days and 14 days after operation in the model group (P<0.05), the expression of Olig2 and Sox10 was increased (P<0.05), and the co-expression of BrdU/NG2 positive cells was increased 7 days and 14 days after operation (P<0.05). Seven days and 14 days after operation, the BBB score in the EA group and medication group was higher than that in the model group (P<0.05), and the co-expression of BrdU/NG2 in the medication group was higher than that in the model group (P<0.05). Fourteen days after operation, the co-expression of BrdU/NG2 in the EA group was higher than that in the model group (P<0.05); 1 day, 7 days and 14 days after operation, the expression of Olig2 and Sox10 in the EA group and medication group was higher than that in the model group (P<0.05). Compared with the medication group, the co-expression of BrdU/NG2 positive cells in the EA group 14 days after operation was decreased (P<0.05); 1 day, 7 days and 14 days after operation, the expression of Olig2 and Sox10 in the EA group was decreased (P<0.05). CONCLUSION: EA at "Jiaji" (EX-B 2) points could promote the expression of Olig2 and Sox10 after spinal cord injury, which has similar effects with GM1. It could promote the proliferation and differentiation of oligodendrocyte precursor cells into oligodendrocytes, so as to promote the recovery of motor function of rats.

Aberrant IGF1-PI3K/AKT/MTOR signaling pathway regulates the local immunity of oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a T cell-mediated immune-related chronic disease, featured by accumulation of T cells and apoptosis of keratinocytes. Insulin-like growth factors 1 (IGF1) signaling, in combination with its downstream PI3K/AKT/MTOR cascade, plays pivotal roles in the regulation of inflammation and immune response. Meanwhile, TRB3 acts as a connective protein in the pathway. This study investigated the possible function of IGF1-PI3K/AKT/MTOR pathway in the local immunity of OLP. METHODS: The expression of phosphorylated IGF1R (p-IGF1R) and TRB3 in lesional tissues of OLP was measured. The effects of T cells pretreated with PI3K inhibitor LY294002, MTOR antagonist rapamycin and exogenous IGF1 on the cell proliferation and apoptosis, as well as supernatant inflammatory cytokine levels were detected in co-culture system of activated T cells and oral keratinocytes, respectively. RESULTS: The expression of p-IGF1R and TRB3 in OLP lesions was significantly increased when compared with controls (P < 0.001). Rapamycin-treated T cells displayed enhanced apoptosis rate and promoted proliferation of their keratinocytes in the co-culture system. Notably, abnormal expression of IFN-γ and IL-4 were detected in supernatant of T cell alone and co-culture system in response to pharmacological modulators of IGF1-PI3K/MTOR pathway. CONCLUSIONS: The aberrant IGF1-PI3K/AKT/MTOR signaling may participate in the immunoregulatory mechanism of OLP, via regulation on the crosstalk between T cells and keratinocytes, as well as imbalanced cytokine networks.

Is dry needling effective for low back pain?: A systematic review and PRISMA-compliant meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of dry needling (DN) for treating low back pain (LBP). METHODS: Nine databases were searched from inception to October 2017. Eligible randomized controlled trials (RCTs) involving DN for treating LBP were retrieved. Two reviewers independently screened the articles, extracted data, and evaluated the risk of bias among the included studies using the risk of bias assessment tool by Cochrane Collaboration. RESULTS: Sixteen RCTs were included and the risk of bias assessment of them was "high" or "unclear" for most domains. Meta-analysis results suggested that DN was more effective than acupuncture in alleviating pain intensity and functional disability at postintervention, while its efficacy on pain and disability at follow-up was only equal to acupuncture. Besides, DN was superior to sham needling for alleviating pain intensity at postintervention/follow-up and functional disability at postintervention. Additionally, qualitative review revealed that DN combined with acupuncture had more significant effect on alleviating pain intensity at postintervention and achieved higher response rate than DN alone. However, compared with other treatments (laser, physical therapy, other combined treatments, etc.), it remained uncertain whether the efficacy of DN was superior or equal because the results of included studies were mixed. CONCLUSIONS: Compared with acupuncture and sham needling, DN is more effective for alleviating pain and disability at postintervention in LBP, while its effectiveness on pain and disability at follow-up was equal to acupuncture. Besides, it remains uncertain whether the efficacy of DN is superior to other treatments. Nevertheless, considering the overall "high" or "unclear" risk of bias of studies, all current evidence is not robust to draw a firm conclusion regarding the efficacy and safety of DN for LBP. Future RCTs with rigorous methodologies are required to confirm our findings. DETAILS OF ETHICS APPROVAL: No ethical approval was required for this systematic review and meta-analysis.