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B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

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Peripheral nerve injury (PNI) is a structural event with harmful consequences worldwide. Due to the limited intrinsic regenerative capacity of the peripheral nerve in adults, neural restoration after PNI is difficult. Neurological remodeling has a crucial effect on the repair of the form and function during the regeneration of the peripheral nerve after the peripheral nerve is injured. Several studies have demonstrated that acupuncture is effective for PNI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve the nervous system remodeling in the process of nerve repair. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating related neurotrophins retrograde transport, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), N-cadherin, and MicroRNAs. Peripheral nerve injury enhances the perceptual response of the central nervous system to pain, causing central sensitization and accelerating neuronal cell apoptosis. Together with this, the remodeling of synaptic transmission function would worsen pain discomfort. Neuroimaging studies have shown remodeling changes in both gray and white matter after peripheral nerve injury. Acupuncture not only reverses the poor remodeling of the nervous system but also stimulates the release of neurotrophic substances such as nerve growth factors in the nervous system to ameliorate pain and promote the regeneration and repair of nerve fibers. In conclusion, the neurological remodeling at the peripheral and central levels in the process of acupuncture treatment accelerates nerve regeneration and repair. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of PNI.

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INTRODUCTION: We implemented a two-sample multivariable Mendelian randomisation (MR) analyses to estimate the causal effect of socioeconomic status and leisure sedentary behaviours on gastro-oesophageal reflux disease (GERD). METHODS: Independent single-nucleotide polymorphisms associated with socioeconomic status and leisure sedentary behaviours at the genome-wide significance level from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) UK Biobank were selected as instrumental variables. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. Univariable and multivariable two-sample MR analyses, using inverse variance weighted method for primary analyses, were performed to jointly evaluate the effect of socioeconomic status and leisure sedentary behaviours on GERD risk. RESULTS: Three socioeconomic status, including educational attainment (OR 0.46; 95% CI 0.30 to 0.69; p<0.001), average total household income before tax (OR 0.65; 95% CI 0.47 to 0.90; p=0.009) and Townsend Deprivation Index at recruitment (OR 1.60; 95% CI 1.06 to 2.41; p=0.026), were independently and predominately responsible for the genetic causal effect on GERD. In addition, one leisure sedentary behaviour, such as time spent watching television, was independently and predominately responsible for genetic causal effect on GERD (OR 3.74; 95% CI 2.89 to 4.84; p<0.001). No causal effects of social activities and driving on GERD were observed. CONCLUSIONS: Genetically predicted Townsend Deprivation Index at recruitment and leisure watching television were causally associated with increased risk of GERD, and age at completion of full-time education and average total household income before tax were causally associated with decreased risk of GERD.

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BACKGROUND: Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD. OBJECTIVE: First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD. METHODS AND ANALYSIS: This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network. CONCLUSION: To collect sufficient medical records and establish models to speed up the process of TCM diagnosis.

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BACKGROUND/AIMS: Metabolic syndrome (MS) has been widely proved as a predictor of cardiovascular disease, all-cause, and cardiovascular mortality in general population. But its effects on mortality and technique failure have not been well illustrated in peritoneal dialysis (PD) patients. We aimed to investigate the association of MS and clinical outcomes in Chinese continuous ambulatory PD (CAPD) patients. METHODS: A single-center, prospective, observational cohort study was conducted in CAPD patients enrolled from September 1 to December 31, 2011, and followed up until December 31, 2016. Demographic, clinical, biochemical and anthropological data were collected. The relationships between MS and mortality and technique failure were assessed using Kaplan-Meier and Cox Regression Survival Functions. RESULTS: A total of 511 patients were enrolled. The baseline mean age was 48.4 ± 14.4 years, 282 patients (55.2%) were male, and 130 patients (25.4%) were diabetic. In total, 213 patients (41.7%) met the diagnostic criterion of MS. During a median of 4.4 years (interquartile range 2.3-5.3 years) follow-up period, 114 patients died, of whom, 65 patients (48%) died in MS group versus 49 patients (30%) in non-MS group. Patients who died tended to be older, higher in inflammation markers and with poorer nutritional state. Kaplan-Meier Survival Functions found patients with MS had a significant rising of all-cause mortality (log-rank test = 12.811, p < 0.001) and cardiovascular mortality (log-rank test = 14.529, p < 0.001) in all patients, and a significant rising of cardiovascular mortality (log-rank test = 4.486, p = 0.034) in non-diabetic patients. After adjusting for confounders, Cox Regression showed that MS was significantly associated with higher cardiovascular mortality in all patients (hazard ratio [HR] 2.21, 95% CI 1.12-4.36, p = 0.022) and in non-diabetic patients (HR 2.60, 95% CI 1.07-6.35, p = 0.036), but it has no significant effect on technique failure. CONCLUSION: In CAPD patients, MS predicted mortality, especially cardiovascular mortality. No relationship was found between MS and technique survival.

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Leaching dynamics of dissolved organic matter (DOM) from agricultural soil are influenced by the chemistry of irrigation water. This study used multiple spectroscopy methods to investigate the dynamics of DOM in column leaching process by utilizing selected solutions. DOC was leached out by Na solutions more effectively than by Ca, despite the additional contributions of the ligand exchange of SO42- and the hydrolysis of HCO3-. The concentration ranking corresponding to solutions is Na2SO4 > NaHCO3 > NaCl > CaCl2. Furthermore, the aromaticity and molecular weights of DOM leached by Na solutions increased with the leaching, whereas contrary trends were reared by Ca. Thus, specific cation substantially affects DOM concentration and composition. Parallel factor analysis of the three-dimensional fluorescence spectra (EEM-PARAFAC) determined the characteristics of DOM components. (1) The long-wavelength, humic-like components (HLC, i.e., C1, C3, and C5) were largely accumulated at the early water saturating stage but attenuated toward dynamic stability in the salt-solution leaching (SSL) stage. (2) Reactive functional group-related HLC (i.e., C2, and C4) remarkably increased in response to the solutions chemistry. (3) The protein-like component (PLC, i.e., C6) was released with insignificant dynamic differences between the solutions. Despite approximately stable DOC concentration at the late stage of each SSL, HLC exhibited accelerating release in sodium salts but declining trend in calcium salt whereas PLC showed a roughly constant dynamic in the both. Ca-bridging reactions with the detachment of OM-Ca-clay complex prompting HLC release and its formation to stabilize the HLC well explain the contrast dynamics of HLC with Na or Ca leaching. The diffusion process that was defined for the slow, lasting and small concentration of leaching of inactive components could contribute to the steady dynamic of PLC, given its insensitivity to either the salt cation. This study identified distinct release kinetics of DOM compositions from those of DOC by EEM-PARAFAC and correspondingly the potential mechanisms, which offers promising advantages in monitoring DOM transport and fractionation in dynamic leaching process.

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Purpose: To investigate the association of T stage and serum carcinoembryonic antigen (CEA) levels in determining oncologic outcomes of rectal cancer. Methods: Patients diagnosed with stage I-II rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results database. Results: In stage T1N0M0 disease, elevated level of serum CEA (C1) was associated with 227.6% increased risk of mortality compared to normal level of serum CEA (C0; hazard ratio = 3.276, 95% confidence interval = 2.781-3.858, P < 0.001). Conclusions: Stage T1N0M0 rectal cancer, when involved in preoperative serum CEA elevation, may be a surrogate of biologically aggressive disease and correlate with unfavorable oncologic outcomes. Moreover, this subgroup of rectal cancer deserves more clinical attention of oncologists.

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AIM: MicroRNAs (miRs) are endogenous substances that act as important diagnostic and treatment targets in renal diseases. miR-146 plays an important role in the development of endotoxin tolerance through NF-κB pathway, but the underlying mechanism is not clearly understood. The aim of this study was to determine the molecular regulation and function of miR-146 and also the expression of miR-146 in an experimental model of renal ischemia reperfusion injury (IRI). METHODS: IRI was induced in mouse by bilateral IRI for 45 min followed by reperfusion. The male mice were randomized as: sham, I/R, I/R+miR-146, and I/R+antago-miR-146 groups. Renal function, histological damage, and cell apoptosis were evaluated at 24 h after reperfusion. RESULTS: Overexpression of miR-146 protected renal function. Renal cells with upregulated miR-146 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, decreased apoptosis and active caspase-3 protein expressions. miR-146 was shown to have a role in renal IR injury. miR-146 has a protective effect on renal function and plays a significant role in apoptosis. IGSF1 acts as a target of miR-146. IGSF1 rescued the effects of miR-146 on renal IRI. miR-146 protected renal function by activation of PI3K/AKT. CONCLUSION: These findings suggest that miR-146 might regulate apoptosis and can cause injury in I/R via targeting IGSF1 and also exert renal protection property.

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The major aim of the present study was to explore the effects of cullin 4B (CUL4B) on the proliferation and invasion of human gastric cancer cells. Gastric tumor tissues and paired adjacent non­tumor tissues were obtained from 21 gastric cancer patients, and gastric cancer cell lines (AGS, MGC­803, KATO­III, MKN­45, SGC­7901, BGC­823 and MKN­74) were cultured. BGC­823 cells were transfected with CUL4B small interfering (si)RNA or control siRNA. Reverse transcription­quantitative polymerase chain reaction analysis was performed to detect the mRNA expression of CUL4B. Western blot analysis was performed to measure the protein levels of Wnt, ß­catenin, glutathione synthase kinase (GSK)­3ß, caspase­3 and cyclin E. MTT and Transwell assays were performed to examine cell proliferation and invasion following CUL4B knockdown. In addition, the effect of CUL4B knockdown on the cell cycle and apoptosis of BGC­823 cells was evaluated by flow cytometric analysis. The results indicated that compared with the adjacent non­tumor tissues and a normal gastric epithelial cell line, gastric cancer tissues and cell lines exhibited significantly higher expression of CUL4B. Knockdown of CUL4B in gastric cancer cells suppressed cell proliferation, caused G1 arrest and inhibited cell invasion. Silencing of CUL4B also resulted in decreased Wnt and ß­catenin expression, but increased expression of GSK­3ß, caspase­3 and cyclin E. These results indirectly demonstrate that CUL4B enhances the proliferation and invasion abilities of gastric cancer cells by upregulating the constituent factors Wnt and ß­catenin, as well as by negatively regulating the mRNA and protein expression of GSK­3ß, caspase­3 and cyclin E. The potential mechanism of CUL4B highlighted in the present study may be helpful for the treatment of patients with gastric cancer.

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BACKGROUND: Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. METHODS: This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. DISCUSSION: We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

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Manganese oxides exhibit an excellent microwave absorption performance that could increase the degradation efficiency of organic pollutants in contaminated water. Incorporation of various transition metals into manganese oxides could bring about changes in their crystal structure and improve their physicochemical performance. In this work, a better microwave absorption material was obtained by adjusting and controlling the electron spin magnetic moments of Fe-doped birnessite. The powder X-ray diffraction, inductive coupled plasma emission spectrometer, X-ray photoelectron spectroscopy, and network analyses were performed to characterize the crystal structure, chemical composition, valence and content of the elements, and the microwave absorption performance of the obtained samples. Doping Fe into birnessite resulted in little changes to their crystal structure. The narrow energy spectrum of Fe (2p) revealed that the doped Fe was in the form of Fe (III) in birnessite structure. As the content of Fe (III) increased, the content of Mn (III) decreased accordingly. Substitution of Mn (III) by Fe (III) in the birnessite crystal lattice, confirmed by combining the characterization analyses with structure refinements for each doped sample, increased the overall numbers of unpaired electrons in birnessite structure, resulting in a higher electron spin magnetic moment and better microwave response. Compared with the non-doped sample, Fe-doped birnessite improved the efficiency of tetracycline degradation, which proved that Fe-doped birnessite indeed had better response towards the microwave, and thus, could be utilized for better removal of organic pollutants under microwave irradiation.

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Acupuncture therapy for regaining consciousness activates soreness, numbness, distention, heaviness, radiating and moving, electric shock and ant climbing sensations at the specific acupoints in the stroke patients. Radiating and moving sensations are the summary of needling sensations such as soreness, numbness and twitching presenting during lifting and thrusting manipulation. These sensations are the essential factors of the therapeutic effect of regaining consciousness. Radiating sensation refers to the conduction along meridians and radiation of soreness and numbness. Moving sensation refers to the local muscular twitching at acupoints and the involuntary movement of limbs, joints and the distal. Acupuncture at the specific acupoints achieves radiating and moving sensations for promoting the circulation in meridians, regulating qi and mind and balancing yin and yang in stroke patients. This therapy was introduced in the paper in view of acupoint location, needle insertion and manipulation.

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BACKGROUND: Recent studies have shown that a protective stoma can reduce morbidity in low anterior resection for rectal cancer; however, the necessity of it is still controversially discussed. METHODS: We performed this meta-analysis to provide a comprehensive evaluation of the role of defunctioning stoma in low anterior resection for rectal cancer on the rates of anastomotic leakage and reoperation related to leakage with or without defunctioning stoma by calculating the pooled risk ratio. RESULTS: Studies and relevant literature published between 2004 and 2014 regarding the construction of a protective stoma after low anterior resection were searched though PubMed and EMBASE databases. Finally, a total of 13 studies including 8,002 patients were included in this meta-analysis. The results indicated that protective stomas significantly reduced the rate of postoperative anastomotic leakage and reoperation after low anterior rectal resection. The pooled risk ratios were 0.47 (95% CI: 0.33-0.68, P <0.0001) and 0.36 (95% CI: 028-0.46, P <0.00001), respectively. CONCLUSIONS: The findings from this present meta-analysis suggest that a defunctioning stoma could effectively reduce the clinical consequences of anastomotic leakage and reoperation, it is recommended in patients undergoing low rectal anterior resection for rectal cancer.

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OBJECTIVE: To observe the effects of blood activating wind dissipating acupuncture (BAWDA) on blood pressure (BP) of prehypertension (PHT) patients. METHODS: Totally 60 PHT patients were assigned to the control group and the acupuncture group according to random digit table, 30 in each group. All patients were intervened by life style. BAWDA was additionally performed in patients in the acupuncture group for 6 weeks (30 times). The improvement of BP after intervened by acupuncture was observed. BP success rates and the proportion of PHT progressing to hypertension (HT) were also observed after 6-week intervention of acupuncture and at 1-year follow-up. RESULTS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased after 6-week intervention in the acupuncture. The BP control rate was 56.7% (17/30 cases) in the acupuncture group vs.10.0% (3/30 cases) in the control group with statistical difference (chi2 = 14.70, P < 0.01). At 1-year follow-up BP success rate was 36.7% (11/30 cases) in the acupuncture group, remarkably higher than that of the control group [13.3%, (4/30 cases)] (chi2 = 4.36, P < 0.05). CONCLUSIONS: BAWDA showed BP regulating roles in a gradually stable decreasing tendency. It also could elevate BP success rate of PHT, and reduce the risk of PHT progressing to HT.

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BACKGROUND: Metabolic syndrome (MS) is prevalent and widely proved as a predictor of cardiovascular disease (CVD) and Type 2 diabetes mellitus (T2DM) in general population. However, there was no large sample study concerning MS in patients on continuous ambulatory peritoneal dialysis (CAPD). We aimed to study the prevalence, risk factors of MS, and the relationship between CVD and MS in CAPD patients in South China. METHODS: This singlecenter cross-sectional study was conducted in patients on CAPD. Demographic, clinical, and anthropometric data were collected and compared between the patients with and without MS. Logistic Regression analysis was used to identify the independent risk factors of MS. RESULTS: A total of 511 CAPD patients were enrolled. Compared to patients without MS, patients with MS tended to be diabetic, female, and older. Fasting waist circumference, waist-to-hip ratio, visceral fat area, as well as white blood cell, platelet, globulin, and high sensitivity C reactive protein in peripheral blood were significantly higher in MS than in non-MS group. But diastolic blood pressure was significantly lower in patients with MS than in patients without MS. Logistic regression showed old age (OR: 1.50, p < 0.001), higher level of WBC (OR: 1.41, p < 0.001), and glucose load of dialysate (GLD) (OR: 1.50, p = 0.002) were independent associated factors of MS and MS was an independent associated factor of CVD (OR: 2.37, p < 0.001). CONCLUSIONS: MS was prevalent in CAPD patients in our center and an independent associated factor of CVD. Old age, higher levels of WBC, and GLD were associated with MS independently.

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