Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.

[Application of body temperature rinse in percutaneous transforaminal endoscopic lumbar discectomy through intervertebral approach].

OBJECTIVE: To investigate the effects of two types of temperature rinses on body temperature, inflammatory cytokine levels, and bleeding volume in percutaneous endoscopic lumbar discectomy. METHODS: Eighty patients underwent percutaneous endoscopic lumbar discectomy from January 2018 to December 2020 were selected and divided into experimental group (40 cases) and control group(40 cases). In experimental group, there were 19 males and 21 females, aged (38.8±9.8) years old;7patients on L4,5 and 33 patients on L5S1;Body msss index(BMI) was (27.8±7.2) kg·m-2. In contral group, there were 18 males and 22 females, aged (41.5±10.9) years old, 5 patients on L4,5 and 35 patients on L5S1;BMI was (26.4±6.2) kg·m-2. The patients in the control group were received normal saline rinse at room temperature, and the patients in the experimental group were received normal saline rinse heated to 37 ℃. Body temperature, chills, nausea, vomiting, and other adverse reactions were recorded. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in two groups were recorded before and 2 hours after operation. Visual analogue scale (VAS) was used to evaluate the degree of lumbar pain in two groups before and 2 hours after surgery. Fibrinolytic-coagulation indexes with preoperative and 2 hours after surgery, including the D-dimer (DD), fibrinogen degradation products (FDP), activated partial thrombin time (APTT) and prothrombin time (PT) were recorder. Operation time and blood loss in two groups were recorded. RESULTS: The body temperature of both groups showed a downward trend, while the body temperature of the control group was lower than that of the experimental group. The levels of TNF-α, IL-6 and IL-10 in two groups were increased 2 hours after surgery compared with those before surgery(P<0.05), while the levels in experimental group were lower than those in control group(P<0.05). Postoperative VAS in experimental group 2.19±1.13 was significantly lower than that in the control group 3.38±1.35(P<0.05). The levels of DD and FDP at 2 hours after surgery in both groups were higher than those before surgery (P<0.05), while the levels of DD and FDP in the experimental group were higher than those in the control group (P<0.05). There was no significant difference in APTT and PT levels between two groups after operation (P>0.05). The blood loss in the experimental group of (45.2±14.1) ml was lower than that in the control group of (59.52±15.6) ml. The operation time of experimental group (46.7±13.8) min was less than that of control group (58.3±15.2) min(P<0.05). CONCLUSION: Body temperature rinse can reduce the incidence of adverse reactions, alleviate local inflammatory reactions, reduce intraoperative blood loss and shorten the operation time.

Research on Mechanism of Nanometric Bone Pulp Activated with Double Gene as Bone Morphogenetic Protein 1 and Vascular Endothelial Growth Factor for Improving the Strength of Centrum in Osteoporosis.

The aim of this study was assessing the mechanism of nanometric bone pulp activated with double gene as bone morphogenetic protein 1 (BMP-1) and vascular endothelial growth factor (VEGF) in improving the strength of centrum in osteoporosis (OP). The model of nanometric bone pulp activated with BMP-1 and VEGF double gene was established and validated. Under maximum condition of load and collapsed fragments, the model was analyzed through biomechanical test. The conditions for ALP, BGP, MLL and BMD in the model were also analyzed, and three-dimensional structural transformation was analyzed. Western blot and qRT-PCR were used to detect the effect of adding or not adding dual gene activated nano-bone stickers on OC-specific protein and mRNA; ELISA kits were used to detect the changes of RANKL pathway RANKL, OPG and TRACP5b. The maximum conformed quality and condensed intensity were strengthened with the nanometric bone pulp activated with BMP-1 and VEGF double gene. The maximum load in centrum was extremely elevated in the model, and the condition of ALP and its effect on bone was partly improved in the model. The precision and efficiency in the quality of BMD were continuously decreased. The BMD and MLF were strengthened notably in the model, and their effect on the bone was extremely improved. There was tight displayed model of trabecular in centrum and porosity was also continuously reduced. After adding the double-gene activated nano-bone stickers, the results from qRTPCR and Western blot showed that the changes of osteoclast-related genes and protein expressions were significantly down-regulated. The nanometric bone pulp activated with BMP-1 and VEGF double gene was one of ideal filled criterion. The BMD and bone strength were also elevated.

Neuron-restrictive silencer factor-mediated downregulation of µ-opioid receptor contributes to the reduced morphine analgesia in bone cancer pain.

Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the µ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively. Additionally, chromatin immunoprecipitation assays were used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was genetically knocked out by antisense oligodeoxynucleotide, and the expression of MOR and the effect of morphine were subsequently analyzed. Our results indicated that in a sarcoma murine model, NRSF expression is upregulated in dorsal root ganglion neurons, and the expression of NRSF mRNA is significantly negatively correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation analysis revealed that NRSF binding to the neuron-restrictive silencer element within the promoter area of the MOR gene is promoted with a hypoacetylation state of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic morphine analgesia. The present results suggest that in sarcoma-induced bone cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of morphine analgesia. Epigenetically, up-regulation of MOR could substantially improve the effect of system delivery of morphine.

Postoperative continuous wound infusion of ropivacaine has comparable analgesic effects and fewer complications as compared to traditional patient-controlled analgesia with sufentanil in patients undergoing non-cardiac thoracotomy.

OBJECTIVE: To compare the postoperative analgesic effects of continuous wound infusion of ropivacaine with traditional patient-controlled analgesia (PCA) with sufentanil after non-cardiac thoracotomy. METHODS: One hundred and twenty adult patients undergoing open thoracotomy were recruited into this assessor-blinded, randomized study. Patients were randomly assigned to receive analgesia through a wound catheter placed below the fascia and connected to a 2 ml/h ropivacaine 0.5% (RWI group) or sufentanil PCA (SPCA group). Analgesia continued for 48 h. Visual analogue scores (VAS) at rest and movement, Ramsay scores and adverse effects were recorded at 2, 8, 12, 24, 36 and 48 h after surgery. Three months after discharge, patient's satisfaction, residual pain and surgical wound complications were assessed. RESULTS: General characteristics of patients were comparable between two groups. There were no statistical differences in the VAS scores and postoperative pethidine consumption between two groups (P > 0.05). However, when compared with SPCA group, the incidences of drowsiness, dizziness and respiratory depression, ICU stay and hospital expenditure reduced significantly in RWI group (P < 0.05). Patients' satisfaction with pain management was also improved markedly in RWI group (P < 0.05). CONCLUSION: Continuous wound infusion with ropivacaine is effective for postoperative analgesia and has comparable effects to traditional PCA with sufentanil. Furthermore, this therapy may also reduce the incidences of drowsiness, dizziness, respiratory depression and decrease the ICU stay and hospital expenditure.

[Influence of histological prostatitis on the clinical features of benign prostatic hyperplasia and prostate cancer].

OBJECTIVE: To investigate the influence of histological prostatitis (HP) on the clinical features of benign prostatic hyperplasia (BPH) and prostate cancer (PCa) and its clinical significance. METHODS: We retrospectively studied the data of 273 cases of BPH and 240 cases of PCa, including age, prostate volume, total prostatic special antigen (tPSA), prostatic special antigen density (PSAD), maximum urinary flow rate (MFR) and acute urinary retention (AUR). RESULTS: Totally, 186 cases of BPH (68.13%) and 45 cases of PCa (18.75%) were complicated by HP, with statistically significant difference between the two groups (P < 0.05). Compared with the patients with BPH only, those complicated by HP showed significantly elevated tPSA, PSAD and total prostate volume (all P < 0.05), decreased MFR (P < 0.05) and increased risk of AUR (P < 0.05). There was no significant difference in the patients' age between the two groups (P > 0.05). The levels of tPSA and PSAD were remarkably higher in the PCa patients complicated by HP than in those with PCa only (all P < 0.05), but no significant differences were found in the other indexes between the two groups (P > 0.05). CONCLUSION: HP may play a certain role in the progenesis and progression of HP and PCa, but HP is associated more closely with BPH.

[Research of the relationship between cervical cytology and HPV test and lesions in the cervical tissue].

OBJECTIVE: Discussion of the relationship between cervical cytology and high-risk HPV test and lesions in the cervical tissue. METHOD: The 254 infertile patients were graded into 4 groups based on the results of cervical cytology and high-risk HPV test. The patients in group A were the cervical cytology -positive and HPV-positive. The cervical cytology -positive and HPV-negative patients were in group B. The cervical cytology -negative and HPV-positive patients were in group C and cervical cytology -negative and HPV-negative in group D. Retrospective analysis was used in the relationship between the results and lesions in the cervical tissue. RESULTS: The incidence of CIN II and higher grade than CIN II was significant higher in group A than in group B (P < 0.01). The incidence of CIN I was no difference among A, B and C group (P > 0.05). The sensitivity was 100.0% and the specificity was 46.74% when cervical cytology was used to test the CIN II grade. But the sensitivity changed to 97.22% and the specificity 87.16% when both of the cervical cytology and HPV test were used. CONCLUSION: The cervical cytology is the first choice in cervical examination. And the accuracy will significant higher when the HPV test is used simultaneously.

[The treatment research of people with different types of HPV infection in sterile patients].

OBJECTIVE: Explore the optimal treatment of infertility patients infected with different types of human papillomavirus (HPV). METHODS: According to cervical pathology, cervical status and the procreate desire of the infertility patients, the 144 clinic cases of high-risk human papillomavirus infected infertile patients were divided into two gruoups: group with treatment and without treatment. Real-time quantitative fluorescent PCR (RT-PCR) has been employed, follow-up time is 6 months, to detect the HPV-DNA in the crevical exfoliated cells, to observe the negative conversion rate and pregnancy rate, and compare analyzed. RESULTS: (1) In high-risk HPV infectors, the negative conversion rate of treatment group (56.67%) is higher than those in non-treatment group (50.00%); (2) The pregnancy rate of secondary high-risk HPV non-treatment group (50.00%) is higher than the treatment group. The pregnancy rate of primary high-risk HPV treatment group (31.67%) is higher than the non-treatment group (4.00%). (3) Negative conversion rate increases accordingly, on primary high-risk HPV infected groups with Leep, with single drug and with Leep combined with drug therapy. (4) The negative conversion rate and the pregnancy rate of primary high-risk HPV infected groups with surgical therapy is higher than the groups with drug therapy. Surgical + Drugs is better in the two surgical therapies. CONCLUSION: Infertile patients should be routinely screened for cervical HPV. The primary high-risk cervical HPV infection is the etiology of infertility. Preferably, patients with primary high-risk HPV infection in cervical lesions is treated with Leep combined drugs.

[Relationship between mycoplasma and chlamydia infection and lesions in the cervical tissue in high-risk HPV-positive patients].

OBJECTIVE: Discussion of the relationship between Mycoplasma and chlamydia infection and lesions in the cervical tissue in high-risk HPV-positive infertile patients with cervical. METHODS: HPV-negative patients with cervical as the control, retrospective analysis the relationship of Mycoplasma hominis and chlamydia infection, cervical histological graded, and inflammation graded. RESULTS: The rate of HPV infection in mycoplasma-positive and those with negative mycoplasma has significant difference (P < 0.01), The rate of HPV infection in chlamydia-positive and those with negative chlamydia has no significant difference (P > 0.05). CIN and the incidence of cervical erosion and CIN grade were higher in HPV-positive than HPV-negative group (P < 0.01). The cervical erosion of HPV-positive was no difference in the degree (P > 0.05). Compared with the simple HPV-positive group, CIN and the incidence of severe cervical erosion in mixed infection of Mycoplasma was no difference (P > 0.05). CONCLUSION: Mycoplasma infection increases the rate of high risk HPV infection, high-risk HPV infection increased cervical pathological damage, Mycoplasma infection might be the factor of persistent infection with high risk HPV, the degree of cervical pathological is the factor of cervical infertility which can not be ignored.

Hopeahainol A: an acetylcholinesterase inhibitor from Hopea hainanensis.

A phytochemical study of Hopea hainanensis has led to the isolation of three new polyphenols and one known compound. The most important of these compounds are hopeahainols A (2) and B (3), which contain an unprecedented carbon skeleton. The structures were elucidated by analysis of the spectroscopic data including single-crystal X-ray spectroscopy and computational methods. Hopeahainol A was an acetylcholinesterase inhibitor with an IC50 value of 4.33 microM, which is comparable to that of huperzine A, a presently prescribed drug for the treatment of Alzheimer, while other similar structures were inactive. This observation was complemented by a 3D interaction model of the inhibitor with active sites.

[Investigation on HPV viral load and high risk HPV types infection among patients with infertility].

OBJECTIVE: High risk human papilomavirus (HPV) infection is often related to cervical cancer. This study investigated the infection of high risk HPV in cervical epithelia among infertile patients. Relative quantification and absolute quantification were applied for determination of "real" HPV viral load in the clinical setting. METHODS: Adopting multi-channels real time PCR to genotype and quantify eight high risk HPV (HPV16, 18, 45, 31; intermediate risk types: HPV33, 52, 58, 67) DNA in cervical epithelia of the 130 infertile patients and the 150 controls. This study applied housekeeping gene (beta-globin) for the DNA quantification on secretions samples for clinical diagnosis. RESULTS: The infection rate of the infertility group was 25.38 percent (33/130) and that of the control group was 11.33 percent (17/150), the difference was statistically significant. Among the 33 positive cases in the infertility group, 24 cases showed a viral load no less than 106; in 9 of them, the viral load was less than 106. Among the 17 positive cases in the control group, 4 cases had a viral load no less than 106; in 13 of them, the viral load was less than 106. There is a statistically significant difference in viral load between the infertility group and the control group. CONCLUSION: The HPV infection rate of the infertility group was higher than that of the control group.

Fiber-modified adenoviral vector expressing the tumor necrosis factor-related apoptosis-inducing ligand gene from the human telomerase reverse transcriptase promoter induces apoptosis in human hepatocellular carcinoma cells.

AIM: Because of a major resistance to chemotherapy, prognosis of hepatocellular carcinoma (HCC) is still poor. New treatments are required and gene therapy may be an option. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in multiple malignant tumors, and using adenoviral vectors has shown a targeted tumor-specific therapy. However, repeated administration of adenoviral vectors can lead to cell resistance, which may be caused by the initial coxsackie-adenovirus receptor (CAR). One technique to overcome resistance is the use of modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence. In this study we constructed an adenoviral vector (designated Ad/TRAIL-F/RGD) with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter, and evaluated its antitumor activity in HCC cell lines. METHODS: To investigate the effects of Ad/TRAIL-F/RGD in human HCC cell lines Hep G2 and Hep 3b, cells were infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control), and Ad/TRAIL-F/RGD. Phosphate-buffered saline (PBS) was used as control. Cell viability was determined by proliferation assay (XTT), and apoptosis induction by fluorescence activated cell sorting (FACS). RESULTS: Cells treated with Ad/TRAIL-F/RGD and Ad/gTRAIL showed a significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP treatment in both cell lines. Whereas, treatment with PBS and Ad/CMV-GFP had no cell-killing effect. The reduced cell viability was caused by induction of apoptosis as shown by FACS analysis. The amount of apoptotic cells was similar after incubation with Ad/gTRAIL and Ad/TRAIL-F/RGD. CONCLUSION: The new RGD modified vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the treatment of HCC, adenovirus resistant tumors, and CAR low or negative cancer cells.