Exploring the mechanism of Ginkgo biloba L. leaves in the treatment of vascular dementia based on network pharmacology, molecular docking, and molecular dynamics simulation.

BACKGROUND: Ginkgo biloba L. leaves (GBLs) play a substantial role in the treatment of vascular dementia (VD); however, the underlying mechanisms of action are unclear. OBJECTIVE: This study was conducted to investigate the mechanisms of action of GBLs in the treatment of VD through network pharmacology, molecular docking, and molecular dynamics simulations. METHODS: The active ingredients and related targets of GBLs were screened using the traditional Chinese medicine systems pharmacology, Swiss Target Prediction and GeneCards databases, and the VD-related targets were screened using the OMIM, DrugBank, GeneCards, and DisGeNET databases, and the potential targets were identified using a Venn diagram. We used Cytoscape 3.8.0 software and the STRING platform to construct traditional Chinese medicine-active ingredient-potential target and protein-protein interaction networks, respectively. After gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of potential targets using the DAVID platform, the binding affinity between key active ingredients and targets was analyzed by molecular docking, and finally, the top 3 proteins-ligand pairs with the best binding were simulated by molecular dynamics to verify the molecular docking results. RESULTS: A total of 27 active ingredients of GBLs were screened and 274 potential targets involved in the treatment of VD were identified. Quercetin, luteolin, kaempferol, and ginkgolide B were the core ingredients for treatment, and AKT1, TNF, IL6, VEGFA, IL1B, TP53, CASP3, SRC, EGFR, JUN, and EGFR were the main targets of action. The main biological processes involved apoptosis, inflammatory response, cell migration, lipopolysaccharide response, hypoxia response, and aging. PI3K/Akt appeared to be a key signaling pathway for GBLs in the treatment of VD. Molecular docking displayed strong binding affinity between the active ingredients and the targets. Molecular dynamics simulation results further verified the stability of their interactions. CONCLUSION SUBSECTIONS: This study revealed the potential molecular mechanisms involved in the treatment of VD by GBLs using multi-ingredient, multi-target, and multi-pathway interactions, providing a theoretical basis for the clinical treatment and lead drug development of VD.

Deep muscle stimulator in the treatment of post-stroke spasticity: A protocol for systematic review and meta-analysis.

BACKGROUND: Spasticity is one of the most common complications and sequelae of stroke, with the main clinical manifestations being increased muscle tension, pain, stiffness, and other disorders. It not only increases the length of hospitalization and medical costs but also affects the quality of daily life and the stress of returning to society, increasing the burden on patients and their families. At present, 2 driver types of deep muscle stimulator (DMS) have been used in the clinical treatment of post-stroke spasticity (PSS) with good clinical results, but there is no evidence of clinical efficacy and safety. Therefore, this study aims to integrate direct and indirect comparative clinical evidence through a systematic review and network meta-analysis (NMA). According to the data, different driver types for DMS with the same body of evidence will be collected, analyzed, and sequenced in a quantitative and comprehensive manner and then screened for the optimal driver type of DMS device for PSS treatment. The study also aims to provide reference value and an evidence-based theoretical basis for the clinical optimization of DMS equipment selection. METHODS: A comprehensive retrieval of China National Knowledge Infrastructure, Chinese scientific journal database, China biological feature database, Wanfang Chinese databases and the Cochrane Library, PubMed, Web of Science, and Embase foreign databases will be conducted. Randomized controlled trials of these 2 driver types of DMS devices combined with conventional rehabilitation training of PSS will be searched and published. The retrieval time is from the establishment of the database to December 20, 2022. The 2 first authors will screen references that meet the inclusion criteria, independently extract data according to predesigned rules, and assess the quality of the included studies and the risk of bias according to the Cochrane 5.1 Handbook criteria. R programming and Aggregate Data Drug Information System software will be used to perform a combined NMA of the data and to evaluate the probability of ranking for all interventions. RESULTS: The NMA and probability ranking will determine the best driver type of DMS device for PSS. CONCLUSION: This study will offer a comprehensive evidence-based approach to DMS therapy and assist doctors, PSS patients, and decision-makers in selecting a more efficient, secure, and cost-effective treatment option.

Exploring the molecular mechanism of Nux Vomica in treating ischemic stroke using network pharmacology and molecular docking methods.

BACKGROUND: Nux Vomica (NV) has the effects of dredging collaterals, relieving pain, dispersing knots, and detumescence, and has a verified effect in treating ischemic stroke (IS), but its molecular mechanism for treating IS remains unclear. In this study, network pharmacology and molecular docking methods were adopted to explore the pharmacological mechanism of NV in treating IS. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the HERB database were searched to screen the active components and targets of NV. IS disease targets were retrieved from the DisGeNET, DrugBank, GeneCards, and Therapeutic Target Database. Venn diagram and intersection targets were obtained from the Venny website. Subsequently, the STRING database was employed to analyze the interrelationship of the intersection targets. Metascape database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection targets. Furthermore, Cytoscape was employed to plot a drug-component-target network, and other networks, and molecular docking method was adopted to predict the effective components and targets of NV for treating IS. RESULTS: A total of 14 active compounds and 59 targets of NV were screened, of which 35 targets were related to IS. Stigmasterol, brucine, isobrucine, isostrychnine N-oxide (I), (S)-stylopine, icaride A, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one were the main active ingredients, and SLC6A4, NR3C1, SLC6A3, HTR3A, CHRNA7, MAOA, PTGS2, ESR1, catalase (CAT), ADRB2, and AR were the core targets. Molecular docking shows that these compounds bind well to the core targets. In addition, the treatment of IS by NV may mainly involve salivary secretion, serotonergic synapse, calcium signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. CONCLUSIONS: This study revealed that NV exerts its therapeutic effect on IS through multi-component, multi-target, and multi-pathway, which provides a basis for clinical treatment of IS.

Efficacy and safety of Jiuhua hemorrhoid suppository plus diosmin for the treatment of hemorrhoid hemorrhage: a multicenter, randomized, and controlled trial / 数字中医药（英文）

Objective@# To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage.@*Methods@#The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration.@*Results@#The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug.@*Conclusion@#Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

Repetitive transcranial magnetic stimulation in patients with fibromyalgia: A protocol for systematic review and network meta-analysis.

BACKGROUND: Fibromyalgia is a chronic disease characterized by widespread pain. Repetitive transcranial magnetic stimulation (rTMS) effectively relieves pain intensity in patients with fibromyalgia. The frequency and target site of rTMS have significant roles in therapy effectiveness. However, there is disagreement over the best rTMS protocol. Thus, we will conduct a thorough systematic review and network meta-analysis to rank the efficacy of these various rTMS protocols and determine which is most beneficial in lowering pain and enhancing the quality of life. METHODS: Databases PubMed, Web of Science, Embase, and Cochrane Library will be searched for clinical randomized controlled trials of rTMS in fibromyalgia. The retrieval time is from the inception of the database until October 1, 2022. Following the Cochrane Handbook, 2 reviewers will independently review the literature, extract data, and evaluate the risk of bias of included articles. Pain intensity and quality of daily life are outcome indicators. Stata 17.0 and ADDIS 1.16.8 software will be used for pairwise meta-analysis and network analysis to evaluate the effectiveness of rTMS and the ranking probability of all protocols. The recommended grading assessment, development, and evaluation will be used to assess the overall quality of the evidence. RESULTS: The meta-analysis and probability ranking of the network determined the best TMS protocol for fibromyalgia. CONCLUSION: This study will provide systematic support of evidence-based medicine for TMS in fibromyalgia, integrate the results of direct and indirect comparisons of the efficacy of different rTMS protocol, and provide the best one.

Theoretical study on thermal decomposition mechanism of 1-nitroso-2-naphthol.

1-nitroso-2-naphthol has thermal instability of thermal decomposition, spontaneous combustion and even explosion. Its thermal decomposition characteristics were tested by synchronous thermal analyzer (TGA/DSC); The activation energy of the thermal decomposition process was calculated by Kissinger method; The infrared absorption characteristic spectra of the gas products produced in the thermal decomposition process were measured by TGA/DSC-FTIR, and the thermal decomposition reaction process was speculated. The results show that the initial temperature (Tonset) of TGA exothermic decomposition of 1-nitroso-2 naphthol is between 129.01 and 155.69 °C, and the faster the heating rate(ß), the higher the Tonset, but the faster the thermal decomposition rate, the greater the heat release and the worse the thermal stability. The activation energy (E) of the thermal decomposition process is 83.323 kJ/mol calculated by Kissinger method. The dynamic test results of TGA/DSC-FTIR show that the main reaction of 1-nitroso-2 naphthol during heating is intermolecular dehydration to form ether, and the secondary reaction is decomposition into aliphatic nitro compounds, carbonyl compounds and amines. Sodium hydroxide will reduce the thermal stability of 1-nitroso-2 naphthol. After adding sodium hydroxide, the thermal decomposition process of 1-nitroso-2 naphthol has changed. The main reaction is that 1-nitroso-2-naphthol reacts with sodium hydroxide to produce sodium nitrophenol, which is further decomposed into aliphatic nitro compounds. The research results have guiding significance for finding the reasonable conditions and temperature of 1-nitroso-2 naphthol during storage and transportation.

Mechanistic Insights into the Protection Effect of Argonaute-RNA Complex on the HCV Genome.

While host miRNA usually plays an antiviral role, the relentless tides of viral evolution have carved out a mechanism to recruit host miRNA as a viral protector. By complementing miR-122 at the 5' end of the genome, the hepatitis C virus (HCV) gene can form a complex with Argonaute 2 (Ago2) protein to protect the 5' end of HCV RNA from exonucleolytic attacks. Experiments showed that the disruption of the stem-loop 1(SL1) structure and the 9th nucleotide (T9) of HCV site 1 RNA could enhance the affinity of the Ago2 protein to the HCV site 1 RNA (target RNA). However, the underlying mechanism of how the conformation and dynamics of the Ago2: miRNA: target RNA complex is affected by the SL1 and T9 remains unclear. To address this, we performed large-scale molecular dynamics simulations on the AGO2-miRNA complex binding with the WT target, T9-abasic target and SL1-disruption target, respectively. The results revealed that the T9 and SL1 structures could induce the departing motion of the PAZ, PIWI and N domains, propping up the mouth of the central groove which accommodates the target RNA, causing the instability of the target RNA and disrupting the Ago2 binding. The coordinated motion among the PAZ, PIWI and N domains were also weakened by the T9 and SL1 structures. Moreover, we proposed a new model wherein the Ago2 protein could adopt a more constraint conformation with the proximity and more correlated motions of the PAZ, N and PIWI domains to protect the target RNA from dissociation. These findings reveal the mechanism of the Ago2-miRNA complex's protective effect on the HCV genome at the atomic level, which will offer guidance for the design of drugs to confront the protection effect and engineering of Ago2 as a gene-regulation tool.

m6A Regulator-Based Exosomal Gene Methylation Modification Patterns Identify Distinct Microenvironment Characterization and Predict Immunotherapeutic Responses in Colon Cancer.

Recent studies have highlighted the biological significance of exosomes and m6A modifications in immunity. Nonetheless, it remains unclear whether the m6A modification gene in exosomes of body fluid has potential roles in the tumor microenvironment (TME). Herein, we identified three different m6A-related exosomal gene modification patterns based on 59 m6A-related exosomal genes, which instructed distinguishing characteristics of TME in colon cancer (CC). We demonstrated that these patterns could predict the stage of tumor inflammation, subtypes, genetic variation, and patient prognosis. Furthermore, we developed a scoring mode-m6A-related exosomal gene score (MREGS)-by detecting the level of m6A modification in exosomes to classify immune phenotypes. Low MREGS, characterized by prominent survival and immune activation, was linked to a better response to anti-PDL1 immunotherapy. In contrast, the higher MREGS group displayed remarkable stromal activation, high activity of innate immunocytes, and a lower survival rate. Hence, this work provides a novel approach for evaluating TME cell infiltration in colon cancer and guiding more effective immunotherapy strategies.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity. Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients. Design, Setting, and Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle. Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion. Main Outcomes and Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12. Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] µg/dL vs 6.1 [3.4] µg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population. Conclusions and Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression. Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.

Prognostic Factors in Stage IV Colorectal Cancer Patients With Resection of Liver and/or Pulmonary Metastases: A Population-Based Cohort Study.

Importance: Currently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient. Objective: To explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC. Methods: The SEER database was used to identify eligible CRC LM and/or PM patients who underwent resection of the primary tumor and distant metastases from January 1, 2010, to December 31, 2018. The Kaplan-Meier method was used to calculate survival, and comparisons were performed using the log-rank test for univariate analysis. A Cox proportional hazards regression model was used to identify prognostic factors for the multivariate analysis. The outcomes included overall survival (OS) and cancer-specific survival (CSS). Results: A total of 3,003 eligible colorectal cancer patients with LM and/or PM were included in this study. The 3-year and 5-year OS rates were 53% and 33.6%, respectively, and the 3-year and 5-year CSS rates were 54.2% and 35.3%, respectively. In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined ≥ 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors. Conclusion: Age < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined ≥ 12 and liver metastases.

Elucidation of the conformational dynamics and assembly of Argonaute-RNA complexes by distinct yet coordinated actions of the supplementary microRNA.

Argonaute (AGO) proteins, the core of RNA-induced silencing complex, are guided by microRNAs (miRNAs) to recognize target RNA for repression. The miRNA-target RNA recognition forms initially through pairing at the seed region while the additional supplementary pairing can enhance target recognition and compensate for seed mismatch. The extension of miRNA lengths can strengthen the target affinity when pairing both in the seed and supplementary regions. However, the mechanism underlying the effect of the supplementary pairing on the conformational dynamics and the assembly of AGO-RNA complex remains poorly understood. To address this, we performed large-scale molecular dynamics simulations of AGO-RNA complexes with different pairing patterns and miRNA lengths. The results reveal that the additional supplementary pairing can not only strengthen the interaction between miRNA and target RNA, but also induce the increased plasticity of the PAZ domain and enhance the domain connectivity among the PAZ, PIWI, N domains of the AGO protein. The strong community network between these domains tightens the mouth of the supplementary chamber of AGO protein, which prevents the escape of target RNA from the complex and shields it from solvent water attack. Importantly, the inner stronger matching pairs between the miRNA and target RNA can compensate for weaker mismatches at the edge of supplementary region. These findings provide guidance for the design of miRNA mimics and anti-miRNAs for both clinical and experimental use and open the way for further engineering of AGO proteins as a new tool in the field of gene regulation.

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that is involved in the development of neuropathic pain. P2X7 receptor (P2X7) belongs to a class of ATP-gated nonselective cation channels that plays an important role in neuropathic pain. Nevertheless, little is known about the interaction between them for neuropathic pain. In this paper, we investigated role of TRPV4-P2X7 pathway in neuropathic pain. We evaluated the effect of TRPV4-P2X7 pathway on neuropathic pain in a chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) model. We analyzed the effect of P2X7 on mechanical and thermal hyperalgesia mediated by TRPV4 in CCD. Furthermore, we assessed the effect of TRPV4 on the expression of P2X7 and the release of IL-1ß and IL-6 in DRG after CCD. We found that intraperitoneal injection of TRPV4 agonist GSK-1016790A led to a significant increase of mechanical and thermal hyperalgesia in CCD, which was partially suppressed by P2X7 blockade with antagonist Brilliant Blue G (BBG). Then, we further noticed that GSK-1016790A injection increased the P2X7 expression of CCD, which was decreased by TRPV4 blockade with antagonist RN-1734 and HC-067047. Furthermore, we also discovered that the expressions of IL-1ß and IL-6 were upregulated by GSK-1016790A injection but reduced by RN-1734 and HC-067047. Our results provide evidence that P2X7 contributes to development of neuropathic pain mediated by TRPV4 in the CCD model, which may be the basis for treatment of neuropathic pain relief.

Femoral nerve block versus fascia iliaca block for pain control in knee and hip arthroplasties: A meta-analysis.

BACKGROUND: This meta-analysis aimed to compare the efficiency of fascia iliaca compartment block (FICB) and femoral nerve block (FNB) for pain management in knee and hip surgeries. METHODS: We searched four electronic databases (Pubmed, Embase, Cochrane library database, Web of Science) from inception to January 2019. Only randomized controlled trials (RCTs) were included. Two review authors independently extracted data for each included study. Primary outcomes were visual analogue scale at 12 hours, 24 hours, 48 hours, total morphine consumption, the length of hospital stay and the occurrence of nausea and vomiting. Standardized mean difference (SMD) or risk ratio (RR) and 95% confidence intervals (CIs) were calculated for continuous outcomes and discontinuous outcomes respectively. We used the Cochrane Risk of Bias tool to assess risk of bias. Stata 12.0 was used for meta-analysis. RESULTS: Finally, 7 RCTs involving 508 patients (FICB = 254, FNB = 254) were included in this meta-analysis. Compared with FNB group, FICB has no benefit for visual analogue scale at 12 hours (SMD = 0.02, 95% CI, -0.15 to 0.19; P = .820), 24 hours (SMD = -0.02, 95% CI, -0.22 to 0.18; P = .806), and 48 hours (SMD = -0.02, 95% CI, -0.22 to 0.19; P = .872). No significant differences were found regarding total morphine consumption (SMD = -0.07, 95% CI, -0.29 to 0.15; P = .533). What's more, there was no significant difference between the length of hospital stay and the occurrence of nausea and vomiting (P > .05). CONCLUSION: FICB has equivalent pain control and morphine-sparing efficacy when compared with FNB. More high-quality RCTs are needed to identify the optimal drugs and volume of local infiltration protocols.

Survival outcomes following laparoscopic vs open surgery for non-metastatic rectal cancer: a two-center cohort study with propensity score matching.

BACKGROUND?>: Laparoscopic surgery for rectal cancer is commonly performed in China. However, compared with open surgery, the effectiveness of laparoscopic surgery, especially the long-term survival, has not been sufficiently proved. METHODS?>: Data of eligible patients with non-metastatic rectal cancer at Nanfang Hospital of Southern Medical University and Guangdong Provincial Hospital of Chinese Medicine between 2012 and 2014 were retrospectively reviewed. Long-term survival outcomes and short-term surgical safety were analysed with propensity score matching between groups. RESULTS: Of 430 cases collated from two institutes, 103 matched pairs were analysed after propensity score matching. The estimated blood loss during laparoscopic surgery was significantly less than that during open surgery (P = 0.019) and the operative time and hospital stay were shorter in the laparoscopic group (both P < 0.001). The post-operative complications rate was 9.7% in the laparoscopic group and 10.7% in the open group (P = 0.818). No significant difference was observed between the laparoscopic group and the open group in the 5-year overall survival rate (75.7% vs 80.6%, P = 0.346), 5-year relapse-free survival rate (74.8% vs 76.7%, P = 0.527), or 5-year cancer-specific survival rate (79.6% vs 87.4%, P = 0.219). An elevated carcinoembryonic antigen, <12 harvested lymph nodes, and perineural invasion were independent prognostic factors affecting overall survival and relapse-free survival. CONCLUSIONS?>: Our findings suggest that open surgery should still be the priority recommendation, but laparoscopic surgery is also an acceptable treatment for non-metastatic rectal cancer.

Rapid rehabilitation technique with integrated traditional Chinese and Western medicine promotes postoperative gastrointestinal function recovery.

BACKGROUND: During the perioperative period, the characteristic therapy of traditional Chinese medicine is effective in improving postoperative rehabilitation. In large-scale hospitals practicing traditional Chinese medicine, there is accumulating experience related to the promotion of fast recovery in the perioperative period. AIM: To evaluate the efficacy and safety of Yikou-Sizi powder hot compress on Shenque acupuncture point combined with rapid rehabilitation technique. METHODS: This prospective, multicenter, randomized, controlled study included two groups: Treatment group and control group. The patients in the treatment group and control group received Yikou-Sizi powder hot compress on Shenque acupuncture point combined with rapid rehabilitation technique and routine treatment, respectively. Clinical observation regarding postoperative recovery of gastrointestinal function was performed, including the times to first passage of flatus, first defecation, and first normal bowel sounds. The comparison between groups was conducted through descriptive analysis, χ 2, t, F, and rank-sum tests. RESULTS: There was a statistically significant difference in the time to postoperative first defecation between the treatment and control group (87.16 ± 32.09 vs 109.79 ± 40.25 h, respectively; P < 0.05). Similarly, the time to initial recovery of bowel sounds in the treatment group was significantly shorter than that in the control group (61.17 ± 26.75 vs 79.19 ± 33.35 h, respectively; P < 0.05). However, there was no statistically significant difference in the time to initial exhaust between the treatment and control groups (51.54 ± 23.66 vs 62.24 ± 25.95 h, respectively; P > 0.05). The hospitalization expenses for the two groups of patients were 62283.45 ± 12413.90 and 62059.42 ± 11350.51 yuan, respectively. Although the cost of hospitalization was decreased in the control group, the difference was not statistically significant (P > 0.05). This clinical trial was safe without reports of any adverse reaction or event. CONCLUSION: The rapid rehabilitation technique with integrated traditional Chinese and Western medicine promotes the recovery of postoperative gastrointestinal function and is significantly better than standard approach for patients after colorectal surgery.

Do cerebral and somatic tissue oxygen saturation measurements correlate with each other during surgery?

Intraoperative maintenance of optimal tissue oxygenation is critical; however, it is uncertain whether measurements of different tissue beds correlate with each other. Cerebral tissue oxygen saturation (SctO2) measured on the forehead and somatic tissue oxygen saturation (SstO2) measured on limbs, using a tissue near-infrared spectroscopy, were simultaneously recorded every 2 s in patients having spine surgery or robotic hysterectomy. Simple linear regression was used to determine the static correlation between SctO2 and SstO2 using the median values of each min for each patient. The dynamic correlation between SctO2 and SstO2 was assessed by Pearson's correlation coefficient (CC) for each non-overlapping 2-min epoch. In patients having spine surgery (n = 99), SctO2 and SstO2 (mean ± SD) were 69.8 ± 4.9% and 75.5 ± 8.7%, whereas in patients having robotic hysterectomy (n = 106), the corresponding values were 74.9 ± 6.8% and 83.7 ± 6.2%. The static correlation between SctO2 and SstO2 was inconsistent (r ranging from - 0.86 to 0.93 in spine surgery and from - 0.74 to 0.85 in robotic hysterectomy). The proportional durations with CC ≤ - 0.3 (negative correlation), - 0.3 < CC < 0.3 (poor correlation) and CC ≥ 0.3 (positive correlation) were 18.3 ± 9.6%, 52.6 ± 12.1% and 29.0 ± 9.6%, respectively, in patients having spine surgery and 19.6 ± 9.0%, 58.6 ± 13.1% and 21.8 ± 8.0%, respectively, in patients having robotic hysterectomy. There are a large discrepancy and inconsistent correlation between intraoperative SctO2 and SstO2 measurements, suggesting their non-interchangeability.

Erosion Failure of a Soil Slope by Heavy Rain: Laboratory Investigation and Modified GA Model of Soil Slope Failure.

Rainfall has been identified as one of the main causes for slope failures in areas where high annual rainfall is experienced. The slope angle is important for its stability during rainfall. This paper aimed to determine the impact of the angle of soil slope on the migration of wetting front in rainfall. The results proved that under the same rainfall condition, more runoff was generated with the increase of slope angle, which resulted in more serious erosion of the soil and the ascent of wetting front. A modified Green-Ampt (GA) model of wetting front was also proposed considering the seepage in the saturated zone and the slope angle. These findings will provide insights into the rainfall-induced failure of soil slopes in terms of angle.

Rational design of type-IA receptor-derived cyclic peptides to target human bone morphogenic protein 2.

Human bone morphogenetic protein 2 (BMP2) is a bone-growth regulatory factor involved in the formation of bone and cartilage, and has been recogn ized as an attractive therapeutic target for a variety of bone diseases and defects. Here, we report successful design of a head-to-tail cyclic peptide based on crystal structure to target BMP2. Computational alanine scanning identifies two hotspot regions at the crystal complex interface of BMP2 with its type-IA receptor; promising one is stripped from the interface to derive a linear self-inhibitory peptide RPS2[r78-94] that covers residues 78-94 of the receptor protein. Dynamics simulation and energetics analysis reveal that the peptide is highly flexible in isolated state and cannot spontaneously bind to BMP2. The RPS2[r78-94] peptide is further extended from its N- and C-termini until reaching two spatially vicinal residues 74 and 98 in the crystal structure of intact BMP2-receptor complex system, consequently resulting in a longer peptide RPS2[r74-98], which is then cyclized in a head-to-tail manner to obtain its cyclic counterpart cycRPS2[r74-98]. Computational analysis suggests that the cyclic peptide can well maintain in a conformation similar with its active conformation in complex crystal structure, exhibiting a smaller disorder and a larger potency than its linear counterpart. Further assays confirm that the two linear peptides RPS2[r78-94] and RPS2[r74-98]are nonbinders of BMP2, whereas, as designed, the cyclic peptide cycRPS2[r74-98] can bind to BMP2 with a moderate affinity. The cyclic peptide is expected as a lead molecular entity to develop new and potent peptide-based drugs for BMP2-targeted therapy.

Peroxisome proliferators-activated receptor gamma polymorphisms and colorectal cancer risk.

AIMS: Several studies evaluated the association between peroxisome proliferators-activated receptor gamma (PPARγ) Pro12Ala (rs1801282), and His477His (rs3856806) polymorphisms and the risk of colorectal cancer (CRC). However, the results were not stable. MATERIALS AND METHODS: We searched databases containing PubMed and EMBASE. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: A significantly decreased CRC risk was found for PPARγ Pro12Ala polymorphism (OR = 0.88, 95% CI 0.83-0.94, P < 0.0001). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.89, 95% CI 0.83-0.95, P = 0.0003) but not in Asian population (OR = 0.76, 95% CI 0.57-1.02, P = 0.07). In the subgroup analysis by CRC location, significantly decreased risks were found in rectal cancer (OR = 0.88, 95% CI 0.77-1.00, P = 0.05) and colon cancer (OR = 0.82, 95% CI 0.73-0.92, P = 0.0008). In addition, a significantly decreased CRC risk was also detected for PPARγ His477His polymorphism (OR = 0.66, 95% CI 0.44-1.00, P = 0.05). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.43, 95% CI 0.26-0.69, P = 0.0006) but not in Asian population (OR = 0.95, 95% CI 0.73-1.25, P = 0.72). CONCLUSIONS: PPARγ Pro12Ala and His477His polymorphisms might be associated with susceptibility of CRC.

[A multicenter, randomized controlled trial of wheat cellulose particles in the treatment of internal hemorrhoids].

OBJECTIVE: To evaluate the efficacy and safety of wheat cellulose particles (testa triticum tricum purify, Fiberform) in the treatment of internal hemorrhoid. METHODS: A multicenter randomized controlled clinical trial was adopted. From October 2015 to July 2016, 60 patients with internal hemorrhoid were enrolled from three medical centers, including Department of Anorectum, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Department of Anorectum, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Anorectum, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine. Enrollment criteria: Patients aging from 18 to 65 years old; being diagnosed with the second or third grade internal hemorrhoid; having good communication skills and being able to complete the records and follow-ups according to the research program requirements. EXCLUSION CRITERIA: Patients combined with other anal diseases, or whose anus tube or rectum suffering occupying lesions; patients currently using other methods and defecation drugs in the treatment of their hemorrhoids; patients in pregnancy or with diseases of heart, liver, kidney or metabolic disorders; patients suffering from constipation due to other diseases and drugs, and long-term laxatives abusers. According to the random number table method, 60 patients were randomly divided into the combined treatment group [30 cases, wheat cellulose particles 1 bag each time, 2 times per day; Diosmin tablet 2 pills, 2 times per day] and the single treatment group [30 cases, Diosmin tablet 2 pills, 2 times per day]. The treatment courses for both groups were 7 days. According to the four-grade scoring method, the efficacy evaluation would be made on six indicators, which were the degree of hematochezia or bleeding, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration. The higher the score a participant got, the more severe the symptom was. The effectiveness was evaluated by the scoring reduction rate, and marked effectiveness and effectiveness were both found to be effective. Incidence of adverse events was compared between two groups before the treatment, and on postoperative 3-day and 7-day respectively. RESULTS: There were no significant differences between two groups in gender, age, internal hemorrhoids gradings, disease course, and onset time as well as the baseline data, such as the degree of hematochezia or bleeding before the treatment, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration (all P>0.05). After the seven-day treatment, there was significant difference in effective rate between combination group and single group [96.7%(29/30) vs. 66.7%(20/30), Z=-4.376, P=0.000]. Meanwhile, the scores of combined group and single group in hematochezia or bleeding were 0(0, 1) and 0(0, 2) (Z=9.241, P=0.002); in shapes and properties of stool were 0(0, 1) and 0(0, 1) (Z=5.364, P=0.021); in defecation frequency were 0(0, 1) and 0(0, 2) (Z=7.552, P=0.006); and in defecation duration were 0(0, 1) and 0(0, 2) (Z=4.425, P=0.035), whose differences were all significant. The scores of pain degree and hemorrhoid prolapse of two groups also decreased, but the difference was not statistically significant (P>0.05). During the treatment, abdominal pain, diarrhea and other adverse reactions were not observed in participants of two groups. CONCLUSION: Combination therapy of wheat cellulose particles (testa triticum tricum purify, Fiberform) can significantly improve the efficacy of internal hemorrhoid with safety and tolerance.