Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain. DATA SOURCES: PubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020. STUDY SELECTION: Randomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included. DATA EXTRACTION: Outcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group. CONCLUSIONS: BTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.

Corticotropin-releasing factor induces inflammatory cytokines via the NLRP6-inflammatory cytokine axis in a murine model of irritable bowel syndrome.

OBJECTIVE: This study aimed to determine the effect of corticotropin-releasing factor (CRF) on regulating the NOD-like receptor pyrin domain-containing protein 6 (NLRP6)-inflammatory cytokine axis in a murine model of irritable bowel syndrome (IBS). METHODS: C57BL/6 mice were subjected to water avoidance stress (WAS) for 1 h per day for 10 days, and the abdominal withdrawal reflex (AWR) and colonic inflammation were assessed. We also measured the levels of CRF, NLRP6 inflammasome components, myeloperoxidase, D-lactate, interleukin (IL)-1ß, and IL-18. In vitro experiments with Caco-2 cell line were also performed. In addition, we assessed the effect of Clostridium butyricum (C. butyricum) on IBS mice. RESULTS: IBS mice exhibited visceral hypersensitivity and inflammation, accompanied by increases in CRF, myeloperoxidase, D-lactate, IL-1ß, and IL-18 levels, but a decrease in NLRP6 expression. In vitro data showed that CRF suppressed NLRP6, but induced IL-1ß and IL-18 levels, in Caco-2 cells. C. butyricum restored CRF levels and maintained the NLRP6-inflammatory cytokine axis in IBS mice. CONCLUSIONS: CRF induces the NLRP6-inflammatory cytokine axis in IBS mice. C. butyricum could be beneficial in controlling IBS.

Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome.

AIM: To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS: In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress (WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry (GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS: WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS (days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A (CoA) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways. CONCLUSION: The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism.

Use of NSAIDs via the Rectal Route for the Prevention of Pancreatitis after ERCP in All-Risk Patients: An Updated Meta-Analysis.

The aim of this study was to assess the efficacy of the rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-ERCP pancreatitis (PEP). We searched database for randomized controlled trials (RCTs) comparing periprocedural rectal administration of NSAIDs with placebo for the prevention of PEP. The rectal administration of NSAIDs significantly decreased the incidence of PEP in the whole patient population (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.30-0.64, P < 0.0001), high-risk patients (OR: 0.34, 95% CI: 0.19-0.58, P = 0.0001), and all-risk patients (OR: 0.51, 95% CI: 0.31-0.84, P = 0.008). The incidence of PEP was reduced by indomethacin (OR: 0.54, 95% CI: 0.36-0.82, P = 0.004) and diclofenac (OR: 0.27, 95% CI: 0.15-0.46, P < 0.00001). The administration of NSAIDs before (OR: 0.42, 95% CI: 0.25-0.73, P = 0.002) or after (OR: 0.39, 95% CI: 0.27-0.56, P < 0.00001) ERCP reduced PEP. The NSAIDs were associated with a reduction in mild PEP (OR: 0.55, 95% CI: 0.36-0.83, P = 0.004) and moderate-to-severe PEP (OR: 0.47, 95% CI: 0.28-0.79, P = 0.004). The rectal administration of NSAIDs reduced the incidence of PEP in high-risk and all-risk patients.

[Diagnosis and Surgical Treatment of Lung Ground-glass Opacities:a Review of 663 Cases].

OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

Mapping of cytotoxic T lymphocytes epitopes in E7 antigen of human papillomavirus type 11.

One of the critical steps in the progression to condyloma acuminatum (CA) is the establishment of a persistent human papillomavirus (HPV) infection, majority of HPV type 6 and 11. Cytotoxic T lymphocytes (CTL), which can be induced by the epitope-based peptides in vitro, are thought to be able to recognize and destroy virus-infected cells. In order to screen and identify HLA-A*0201 restricted HPV-11E7 CTL epitopes, five epitope peptides and tetramers were selected including HPV-11E7 7-15 (TLKDIVLDL), 15-23 (LQPPDPVGL), 47-55 (PLTQHYQIL), 81-89 (DLLLGTLNI) and 82-90 (LLLGTLNIV). Human monocyte-derived dendritic cells (DCs) from HLA-A*0201 healthy individuals were pulsed with these peptides to assess the expression of CD83, CD86, HLA-DR and the secretion of IL-12. The ability of peptide-loaded mature DCs to activate autologous T cells was evaluated by analyzing the frequency of specific tetramer(+) CD8(+) T cells using flow cytometry, and the level of IFN-gamma secretion by ELISA. The ability of the epitope-specific CTLs to kill the target cells was also analysed. It was found that the immature DCs could be fully activated by all the five HPV-11E7 peptides and peptide-loaded mature DCs were able to stimulate the epitope-specific T cells in vitro. There was an increased frequency of CD8(+) T cells specific for the E7 7-15 epitope when compared to other four predicted epitopes of HPV-11E7 (P < 0.05). The epitope-specific CTLs for E7 7-15 induced the strongest cytotoxicity to HPV-11E7 expressing cell line at an E:T ratio of 50:1 (P < 0.05). Taken together, these findings demonstrate that E7 7-15 (TLKDIVLDL) is an HLA-A*0201-restricted CTL epitope of HPV type 11. We propose that this epitope could be more helpful in the characterization of HPV control mechanism and be useful for the development of immunotherapeutic approaches for low-risk HPV infectious diseases such as CA.

[HPV DNA vaccines expressing recombinant CRT/HPV6bE7 fusion protein inhibit tumor growth and angiogenic activity].

This paper was to study the angiogenic inhibitory effect and the potential antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo. The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To investigate the potential antitumor effect, the mean tumor weights, sizes and tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7-expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7 and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was superior to other vaccines in delaying tumor formation time, limiting tumor size and weight in tumor protection experiment. In conclusion, recombinant CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic activity of CRT were suggested residing in a domain between CRT 120-180 aa.

[The construction and immune response of fusion DNA vaccine CRT180/HPV6E7].

OBJECTIVE: To investigate the immune response, in particular, the anti-virus cellular immune response induced by the constructed fusion DNA vaccine CRT (Calreticulin) 180/HPV6E7 in vivo and vitro. METHODS: The HPV6E7 open reading frame was amplified by polymerase chain reaction from pUC/HPV6 plasmid. The CRT180 gene was cloned by reverse transcription from human muscle tissues. The PCR products of CRT180 and HPV6E7 were subcloned into pcDNA3. 1-GFP eukaryotic vector. The recombinant plasmids CRT180/ HPV6E7 was authenticated by restrict enzyme digestion and confirmed by DNA sequencing. The DNA plasmid HPV6E7 with report gene GFP was transfected to murine B16 cells by lipofectamine kit to establish the target cells. The HPV6E7-expressing cell line was selected by G418 and identified by RT-PCR. The C57BL/6 mice were vaccinated via intramuscular injection in the right legs with 100 microg plasmid encoding CRT180-HPV6E7, CRT180 or HPV6E7, empty plasmid without insert, and PBS group respectively. The changes of the T lymphocyte subsets in the peripheral blood of the mice were evaluated by flow cytometric analysis. The lymphocytes from the spleen and lymph nodes were harvested and co-cultured with HPV6E7-expressing cell lines. The CTLs kill activity and the cytokines IL-2, IFN-gamma secretion levels of the lymphocytes were assessed by LDH and ELISA respectively. RESULTS: The constructed recombinant plasmids pcDNA3. 1-CRT180/HPV6E7, pcDNA3. 1-CRT180 and pcDNA3. 1-HPV6E7 were authenticated by restrict enzyme digestion and confirmed by DNA sequencing. Green fluorescence located in the cellular nucleus and plasma could be detected by fluorescent microscope after transfection with plasmids. The results of RT-PCR from the selected positive cell line showed the expected fragments of HPV6E7 mRNA. After immunization, the percentage of CD8+ or TCRgamma delta tau cells in the peripheral blood, the CTLs kill activity of the spleen cells and lymphocytes against HPV6E7-expressing cells, and the secretion levels of IL-2, IFN-gamma in CRT180/HPV6E7 vaccinated group increased significantly compared with the control groups (P < 0.05). CONCLUSION: Vaccination with fusion DNA vaccine CRT180/HPV6E7 could elicit a more efficient HPV6E7-specific immune response than with HPV6E7 plasmid, indicating the potential of CRT180/HPV6E7 vaccine to enhance the antigen presentation. The recombinant CRT180/HPV6E7 might help the elimination of virus in animal models and accordingly be used as a vaccine candidate in the therapy of CA.

Recombined DNA vaccines encoding calreticulin linked to HPV6bE7 enhance immune response and inhibit angiogenic activity in B16 melanoma mouse model expressing HPV 6bE7 antigen.

Calreticulin (CRT) has been reported to have an effect of upregulating MHC class I presentation as well as inhibiting angiogenesis in vitro and in vivo. Combination of dual mechanisms of enhanced immunogenicity of human papillomavirus (HPV) 6bE7 antigen and antiangiogenesis may be introduced in the strategy of vaccines against condyloma acuminatum (CA) resulting from HPV infection. Therefore, we constructed DNA vaccines by employing different lengths of CRT chimerically linked to a model antigen HPV6bE7 and investigated the immunological and antiangiogenic effects of these vaccines in a B16 melanoma model that express HPV6bE7 antigen. Our results showed that vaccination with CRT180/HPV6bE7 or CRT120/HPV6bE7 enhanced the presence of CD8(+) T cells and TCRgammadelta T cells in vivo, increased the specific lysis activity against E7-expressing cells and secretion levels of IL-2 and IFN-gamma by activating T cells in vitro significantly. Moreover, recombined CRT180 or CRT120 with HPV6bE7 vaccines could elicit a more efficient E7-specific immune response than HPV6bE7 alone. The similarity of immunological enhancement of CRT180/HPV6bE7 and CRT120/HPV6bE7 implies that the immunologically active region mainly exist in fragment 1-120 aa. Furthermore, CRT180/HPV6bE7 and CRT180 displayed remarkable superiority over CRT120/HPV6bE7 in vivo angiogenesis assay, suggesting that the antiangiogenic activity of CRT resides in a domain between aa 120 and 180. Vaccination with CRT180/HPV6bE7 generated the best protective effect of delaying tumor formation and reduction of tumor size in tumor growth inhibition experiment among all DNA constructs. Therefore, CRT180/HPV6bE7 vaccine may enhance the immunological response to HPV6bE7 and inhibit angiogenesis. This construct may be useful in preventing HPV-associated dermatosis and may be developed as a promising strategy to control CA.