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The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd–6th min ( post A), and 7th–10th min ( post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased significantly ( post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly ( post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat−1·mmHg−1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings.

Xianglong Cao, Jian Cui, Zijian Li, Gang Zhao Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Gang Zhao Email zhaogang3221@163.comBackground: Systemic inflammation and malnutrition may promote tumor progression. C-reactive protein/albumin ratio (CAR) is linked to the poor long-term survival of several malignant tumors.Purpose: To explore the predictive value of CAR in gastrointestinal stromal tumors (GISTs).Methods: A retrospective study was conducted on 325 patients with primary GIST surgically treated with curative intent from 2009 to 2018. The cut-off point of CAR was set using X-tile software. Kaplan–Meier method and multivariate Cox regression model were used to study the prognostic value of CAR. The time-dependent receiver operating characteristic curve (tROC) was drawn, and the prognostic accuracy of CAR, Glasgow prognostic score (GPS), and National Institute of Health (NIH) risk classification was compared by the area under the curve (AUC).Results: The best cut-off point of CAR was 0.55. Increased CAR was associated with the location of the lower digestive tract, larger tumor size, higher mitotic index, higher NIH risk classification, lower ALB, higher CRP, and higher GPS (all p< 0.05). Multivariable analysis revealed that CAR (hazard ratio [HR] 2.598, 95% confidence interval [CI] 1.385– 4.874; p=0.003) was an independent predictor of overall survival. Additionally, the AUC of CAR was lower than that of NIH risk classification at 2 years (0.601 vs. 0.775, p=0.002) and 5 years (0.629 vs 0.735, p=0.069). However, the AUC of NIH risk classification significantly increased (2-year OS 0.801, p=0.251; 5-year OS 0.777, p=0.011) when combined with CAR.Conclusion: CAR is a new independent predictor of poor survival in patients with GIST. CAR combined with NIH risk classification can effectively improve the performance of prognosis prediction.Keywords: gastrointestinal stromal tumor, C-reactive protein, C-reactive protein/albumin ratio, prognosis

Background Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects. Case Presentation Here, we report a case of a patient with NSCLC with an EML4-ALK fusion and was treated with alectinib but who developed grade 4 hyperbilirubinemia after five months on therapy. Alectinib was discontinued, and an artificial liver support system (ALSS) was used with an impressive decline in bilirubin levels. After two months drug-free, the patient experienced disease progression. Ensartinib was initiated as second-line treatment with a best response of stable disease after three months of therapy with no evidence of hyperbilirubinemia. Conclusion This is the first report of ensartinib treatment after alectinib-induced hyperbilirubinemia which was successfully relieved by ALSS treatment and targeted drug cessation.

To investigate the impact of the COVID-19 pandemic on patients with colorectal cancer undergoing elective surgery. The medical records of patients with colorectal cancer who underwent elective surgery in our department during the COVID-19 pandemic (February 1 to May 31, 2020) were collected and analyzed. We compared the clinical data with colorectal cancer during the same 4-month period in 2018 and 2019. Sixty-seven patients with colorectal cancer underwent elective surgery during the COVID-19 pandemic. This was 66% of the number of patients that underwent the procedure during the same period in 2018 and 2019. During the COVID-19 pandemic, the proportion of patients without any digestive system symptoms decreased to 3% and severe clinical symptoms decreased by 20.9%. The proportion of right colon cancer decreased by 17.9%, while the proportion of rectal cancer increased by 52.2%, as compared with 2018 and 2019. The fraction of protective stoma was significantly higher than in 2018 (23.9% vs. 8.7%, p = 0.011). Compared with 2019, the average post-operative stay was significantly shorter than in 2018 (9.6 ± 3.7 vs. 12.1 ± 9.1, p = 0.015). Compared with 2019, the number of patients with perineural invasion (a feature of adverse prognosis) significantly increased (p = 0.009). During the COVID-19 pandemic, the number of patients undergoing elective surgery for colorectal cancer was reduced. However, the tumor stage of patients did not change substantially. We suggest that the clinical diagnosis and treatment of colorectal cancer should strictly comply with national and professional standards.

Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3rd agent, were enrolled from 2017. Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow. The correlation between Bregs and clinical characters were further analyzed. This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM. The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here. This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM. Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.

Background Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value. Materials and Methods The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan-Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model. Results CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls (P < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage (P = 0.039) and distant metastasis (P = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels (P = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS. Conclusion Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma.

Background and Introduction: Collateral circulation is very crucial for the prognosis of stroke patients. Transcranial color-coded duplexsonography (TCCD) is used widely to evaluate the intracranial arterial blood flow. However, approximately 20% - 30% of the patients with cerebral infarction cannot be detected via TCCD due to the interruption of thickened temporal bones. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (CE-TCCD) in stroke patients with limited bone windows. Methods: CE-TCCD was applied to 70 patients (51 males and 19 females) who presented with ischemic symptoms, to detect the openness of the anterior communicating artery (ACoA) and posterior communicating artery (PCoA) of the Willis ring before Computed Tomography angiography (CTA) or Magnetic Resonance Angiography (MRA) examination. The results from CETCCD is used to compare with CTA/MRA result to verify the diagnostic efficacy. Results: Forty-one communicating artery openings were detected by CE-TCCD, among which 37 were PCoA and 4 were ACoA. Among the 70 patients, 23 of 70 patients indicated severe stenosis within intracranial and/or extracranial arteries. Eighteen out of the 23 patients showed collateral circulation, accounting for 78.3% (18/23). Moderate stenosis were 23 cases in total, in which 7 cases showed collateral circulation, accounting for 30.4% (7/23). Slight stenosis were 24 cases in total, none of which showed collateral circulation. Conclusion : In the stroke patients with limited bone windows, CE-TCCD can evaluate intracranial collateral circulation.

Objective: This study was aimed to elucidate the feasibility of using right ventricular (RV) strain and strain rate to evaluate right heart function of Ebstein anomaly (EA) patients before and after operation. Methods: Sixty EA patients and 30 healthy controls underwent echocardiography (UCG) for evaluation of right heart function. Preoperative UCG and 1-week and 3-month postoperative UCG were performed in EA patients. RV strain and strain rate were measured on the four-chamber section of tissue Doppler imaging (TDI). Results: The strain and strain rate representative of right ventricle systolic function were reduced prior to operation. RV strain and strain rate improved after the operation (P < .001), most significantly in the basal segment and middle segment of the free wall of the right ventricle as well as the basal segment of the interventricular septum (P < .001). Conclusions: The measurement of RV strain and strain rate on tissue Doppler imaging can be employed to assess the preoperative and postoperative RV function, proves the positive effect of tricuspid valve repair on right heart function, and offers more insight on right heart function evaluation.

Background Defunctioning stoma is widely used to reduce anastomotic complications in rectal cancer surgery. However, the complications of stoma and stoma reversal surgery should not be underestimated. Furthermore, in some patients, stoma reversal failed. Here, we investigated the complications of defunctioning stoma surgery and subsequent reversal surgery and identify risk factors associated with the failure of getting stoma reversed. Methods In total, 154 patients who simultaneously underwent low anterior resection and defunctioning stoma were reviewed. Patients were divided into two groups according to whether their stoma got reversed or not. The reasons that patients received defunctioning stoma and experienced stoma-related complications and the risk factors for failing to get stoma reversed were analysed. Results The mean follow-up time was 47.54 (range 4.0–164.0) months. During follow-up, 19.5% of the patients suffered stoma-related long-term complications. Only 79 (51.3%) patients had their stomas reversed. The morbidity of complications after reversal surgery was 45.6%, and these mainly consisted of incision-related complications. Multivariate analyses showed that pre-treatment comorbidity (HR = 3.17, 95% CI 1.27–7.96, P = 0.014), postoperative TNM stage (HR = 2.55, 95% CI 1.05–6.18, P = 0.038), neoadjuvant therapy (HR = 2.75, 95% CI 1.07–7.05, P = 0.036), anastomosis-related complications (HR = 4.52, 95% CI 1.81–11.29, P = 0.001), and disease recurrence (HR = 24.83, 95% CI 2.90–213.06, P = 0.003) were significant independent risk factors for a defunctioning stoma to be permanent. Conclusions Defunctioning stoma is an effective method to reduce symptomatic anastomotic leakage, but the stoma itself and its reversal procedure are associated with high morbidity of complications, and many defunctioning stomas eventually become permanent. Therefore, surgeons should carefully assess preoperatively and perform defunctioning stomas in very high risk patients. In addition, doctors should perform stoma reversal surgery more actively to prevent temporary stomas from becoming permanent.

Background China media reported infant deaths following hepatitis B vaccination in late 2013, leading to temporary suspension of hepatitis B vaccine (HepB Event) until the deaths were shown to be coincidental and the vaccine was of standard, good quality. In 2016, a criminal ring in Shandong province that had been purchasing, improperly storing, and reselling Category 2 vaccines (private-sector) to 60 (of 200,000) clinics for 5 years, was exposed, publicized, and prosecuted, and the potential health and epidemiological impacts were investigated to determine whether revaccination was necessary (Shandong Vaccine Event). Methods We assessed parental confidence in vaccines through 9 telephone surveys in 6 and 11 provinces before, during, and after the two events. Provider confidence was assessed through in-person interviews following each event. Vaccine utilization was assessed using Immunization Information Management System data from township clinics. Results In the early stages of each event, approximately 30% of parents indicated vaccine hesitancy and 18% said they would refuse routine immunization. Five and nine months after each event, hesitancy and refusal decreased, but not to pre-event levels. During the Shandong Vaccine Event, 49·1% of parents indicated refusal to use Category 2 vaccines; six months later, the rate was 32·8%. Use of HepB decreased by 21% during the first 2 weeks of the HepB Event and by 12·6% during the first 4 weeks of Shandong Vaccine Event, but returned to baseline in less than 3 months. Use of Category 2 vaccine decreased by 49·5% in the first 3 weeks of the Shandong Vaccine Event and by 28·7% 6 months later. After the Shandong Vaccine Event, 64% of clinicians held high confidence in routine immunization, lower than at baseline. Conclusions The two events caused mistrust, loss of confidence, and decreases in use of vaccines by parents and providers. In addition to ensuring immunization program integrity, effective communications and ongoing monitoring of vaccine use and confidence should be included to restore confidence and trust in vaccines.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: does percutaneous transthoracic needle biopsy (PTNB) increase the risk of pleural recurrence in patients with stage I lung cancer? Altogether, 298 papers were found using the reported search, of which 7 cohort studies and 1 meta-analysis represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Four cohort studies suggested an association between PTNB and pleural recurrence in patients with stage I lung cancer, while the other 3 cohort studies found that PTNB had no impact. One meta-analysis (the largest study) including 5 of the cohort studies above concluded that PTNB increased the risk of pleural recurrence among patients with stage I lung cancer with subpleural lesions. Based on the available evidence, it was suggested that there may be an association between PTNB and pleural recurrence in patients with stage I lung cancer, especially for patients with subpleural lesion.

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([Formula: see text]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [Formula: see text] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Background and objective As a common pathological pulse, unsmooth pulse has important diagnostic value in traditional Chinese medicine (TCM). In modern pulse diagnosis, unsmooth pulse plays an important role in the diagnosis of disease location and nature, but there are few studies on it. In this paper, a pulse diagnosis approach based on acoustic waveforms was proposed, the wrist pulse was divided into five layers vertically for the first time. Five layers acoustic waves of the radial artery in stable coronary heart disease (CHD) patients and relatively healthy people were compared to explore whether there are abnormal changes in acoustic pulse in stable CHD patients. Methods The acoustic features of unsmooth pulse in patients with stable CHD were analyzed in time domain, frequency domain and empirical mode decomposition, combined with shannon entropy and multi-scale entropy. Sixteen pulse characteristics were discovered, and one-way analysis of variance were performed. The characteristics of the two groups were tested by T test. 13 features were used to identify patients with stable CHD by support vector machine (SVM). Results Compared to healthy people, all parameters of the third layer of the stable CHD left Cun pulse were significantly different from those of the healthy people. The identification rates of the fourth and third layer of the left Cun pulse were the first (90.79%) and the second (88.16%), respectively. Conclusion Abnormal acoustic pulse appeared in the radial artery in patients with stable CHD. According to these changes, patients with stable CHD can be effectively identified from the perspective of pulse.

Smoking is a risk factor for cardiovascular diseases. Prior reports showed a transient increase in blood pressure (BP) following a spontaneous burst of muscle sympathetic nerve activity (MSNA). We hypothesized that this pressor response would be accentuated in smokers. Using signal-averaging techniques, we examined the BP (Finometer) response to MSNA in 18 otherwise healthy smokers and 42 healthy nonsmokers during resting conditions. The sensitivities of baroreflex control of MSNA and heart rate were also assessed. The mean resting MSNA, heart rate, and mean arterial pressure (MAP) were higher in smokers than nonsmokers. The MAP increase following a burst of MSNA was significantly greater in smokers than nonsmokers (Δ3.4 ± 0.3 vs. Δ1.6 ± 0.1 mmHg, P < 0.001). The baroreflex sensitivity (BRS) of burst incidence, burst area, or total activity was not different between the two groups. However, cardiac BRS was lower in smokers than nonsmokers (14.6 ± 1.7 vs. 24.6 ± 1.5 ms/mmHg, P < 0.001). Moreover, the MAP increase following a burst was negatively correlated with the cardiac BRS. These observations suggest that habitual smoking in otherwise healthy individuals raises the MAP increase following spontaneous MSNA and that the attenuated cardiac BRS in the smokers was a contributing factor. We speculate that the accentuated pressor increase in response to spontaneous MSNA may contribute to the elevated resting BP in the smokers.

To assess patients with multiple myeloma (MM), the whole-body positron-emission tomography/computed tomography (PET/CT) occupies a pivotal position for diagnostic stratification, response evaluation, and survival prediction, while important limitations are recognized as incapable of representing tumor microenvironment. Regulatory B cells (Bregs) have been reported to have an inhibitory immune function, contributing to bone marrow (BM)-immunosuppressive microenvironment for MM. Therefore, to investigate the role of PET/CT in combination with Bregs’ ratios to predict therapeutic response and survival, we sequentially enrolled 120 patients with newly diagnosed MM (NDMM) who were treated with novel agents in our center, while conventional PET/CT parameters including maximum standard uptake value (SUVmax), ratios of BM-derived Bregs within CD19+ B cells, and patients’ clinical characteristics were collected. After a median follow-up of 28.20 months (range 7.00–46.93 months), SUVmax > 4.2 at onset, accounting for 53.2% of NDMM, was uncovered to predict inferior progression-free survival (PFS) as well as overall survival (OS). With regard to the ratios of BM-derived Bregs within CD19+ B cells, the cohort with the Bregs’ proportions lower than 10%, accounting for 46.2%, exerted poorer OS. Additionally, the patients with both SUVmax > 4.2 and Bregs’ ratios < 10%, accounting for 31.7%, yielded compromised therapeutic response and long-term survival. Collectively, this study may draw attention on the prognostic value of combination of PET/CT and Bregs’ ratios when clinical decisions are made for MM in the era of novel agents.

Crosstalk between coagulation and innate immunity contributes to the progression of many diseases, including infection and cardiovascular disease. Venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis (DVT), is among the most common causes of cardiovascular death. Here, we show that inflammasome activation and subsequent pyroptosis play an important role in the development of venous thrombosis. Using a flow restriction–induced mouse venous thrombosis model in the inferior vena cava (IVC), we show that deficiency of caspase-1, but not caspase-11, protected against flow restriction–induced thrombosis. Interleukin-1β expression increased in the IVC following ligation, indicating that inflammasome is activated during injury. Deficiency of gasdermin D (GSDMD), an essential mediator of pyroptosis, protected against restriction-induced venous thrombosis. After induction of venous thrombosis, fibrin was deposited in the veins of wild-type mice, as detected using immunoblotting with a monoclonal antibody that specifically recognizes mouse fibrin, but not in the caspase-1–deficient or GSDMD-deficient mice. Depletion of macrophages by gadolinium chloride or deficiency of tissue factor also protected against venous thrombosis. Our data reveal that tissue factor released from pyroptotic monocytes and macrophages following inflammasome activation triggers thrombosis.

Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing ‘disorderliness’ of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular ‘order’ and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.

Prior reports show that whole body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole body heating (WBH; e.g., increase in internal temperature Tcore of ∼0.4°C–0.5°C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remain unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and heart rate (HR) in 14 older (62 ± 2 yr) healthy subjects during fatiguing isometric handgrip exercise and postexercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH, and local limb (i.e., forearm) heating conditions during three visits. During the mild WBH stage (increase in Tcore of core of ∼0.4°C), BP decreased, HR increased, and MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO was lower during the WBH trial. Moreover, MSNA and MAP responses (i.e., changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature to that seen in the WBH trial (∼0.7°C–1.5°C). Limb heating did not alter resting MAP, HR, or MSNA. The MSNA and hemodynamic responses to exercise in the limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans.

Radical resection with or without adjuvant chemotherapy is a common option for stage II and III colorectal cancer. Few reports exist regarding gastric tumorigenesis, including gastric cancer, gastric intraepithelial neoplasia, and gastric stromal tumor, in patients who received this protocol as the standard treatment for colorectal cancer. We present two cases of gastric tumorigenesis in patients with colorectal cancer following radical resection combined with adjuvant chemotherapy. Both patients underwent gastrectomy and D2 lymphadenectomy for their gastric tumors; neither patient developed recurrence up to 2 years after treatment. These cases indicate that patients should be monitored closely for gastric tumorigenesis after treatment for colorectal cancer. Early detection and active surgical treatment can provide satisfactory results for colorectal cancer followed by gastric tumorigenesis. Long-term follow-up and regular examinations, especially gastroscopy, are necessary to detect gastric tumorigenesis after colorectal cancer. The focus on monitoring colorectal cancer alone in colorectal cancer patients should be changed to include a broader range of cancers in addition to precancers and other tumors, such as gastric stromal tumor.

This study was to evaluate the biomechanical characteristics of the vascular wall during virtual reality- (VR-) assisted percutaneous transluminal angioplasty (PTA) and its effect on the treatment of lower-extremity arteriosclerosis obliterans (LEAO). In this study, a three-dimensional (3D) model and a finite-element model of arteries were constructed first, and various fluid mechanics were analyzed. Then, the virtual expansion simulation (VES) of individualized PTA was performed based on the ABAQUS/Explicit module to analyze the interaction between the balloon and the blood vessel at different times and the changes in the vascular shape and structural stress distribution. Finally, an LEAO animal model was constructed. Based on conventional PTA (PTA group) and VR-assisted PTA (VR-PTA) treatment, the morphological changes of vascular lumen of the two animal models were evaluated. The results showed that the normal, stenotic blood vessels and blood models were successfully constructed; the pressure of the stenotic blood vessel at the stenosis decreased obviously and the shear stress of blood vessel wall increased compared with that of the normal blood vessels, and there may be a blood reflux area in the poststenosis stage. The simulation results of the VES showed that the maximum principal stress value at 3 mm of the marginal vessel was much lower than that at 5 mm (about 10% lower), so the maximum principal stress change within 2 mm of the balloon-expanded vessel was the most obvious. The treatment results of the animal model showed that the VR-PTA group showed an obvious increase in the diameter of the vascular lumen, a decrease in the intima and media area, and a decrease in the thickness of the vessel wall in contrast to the PTA group P < 0.05 , which had an important effect on the reconstruction and expansion of the vascular lumen. The VR-PTA treatment on LEAO was realized in this study, which provided critical reference for the follow-up application of VR technology in the evaluation of surgical plan and research on biomechanical mechanisms of restenosis after PTA.

Background Systemic inflammation and malnutrition may promote tumor progression. C-reactive protein/albumin ratio (CAR) is linked with poor long-term survival of several malignant tumors.Purpose To explore the predictive value of CAR in gastrointestinal stromal tumors (GISTs).Methods A retrospective study was conducted on 325 patients with GIST who underwent radical surgery from 2009 to 2018. The cut-off point of CAR was set using X-tile software. Kaplan-Meier method and multivariate Cox regression model were used to study the prognostic value of CAR. The time-dependent receiver operating characteristic curve(tROC) was drawn, and the prognostic accuracy of CAR, Glasgow prognosis score (GPS), and NIH risk classification was compared by the area under the curve (AUC).Results The best cut-off point of CAR was 0.55. Increased CAR was associated with the location of the lower digestive tract, larger tumor size, higher mitotic index, higher NIH risk classification, lower ALB, higher CRP, and higher GPS (all pConclusions CAR is a new independent predictor of poor survival in patients with GIST. CAR combined with NIH risk classification can effectively improve the performance of prognosis prediction.

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; −10, −20, and −30 mmHg), as renal oxygenation was measured (T2*, blood oxygen level dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured (n = 13) as LBNP was instituted. LBNP significantly reduced RBV (P = 0.041) at −30 mmHg of LBNP (Δ−8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first minute of recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla. NEW & NOTEWORTHY In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.

Inflammatory bowel disease (IBD) is a worldwide prototypical complex disease, owing to its multifactorial causes, relapsing and remitting condition and high incidence. Thus, effective therapeutic approaches need to be developed for patients with IBD. Currently, we reported the improving effect of magnesium isoglycyrrhizinate on colitis induced by dextran sulfate sodium (DSS). We found that magnesium isoglycyrrhizinate treatment significantly alleviated DSS-induced acute and chronic colitis by inhibiting the inflammatory response characterized by reduce of the infiltrations of immune cell and the level of pro-inflammatory cytokines. Besides, magnesium isoglycyrrhizinate treatment significantly inhibited the level of ROS and decreased the gut barrier destruction after DSS treatment. Furthermore, the results also showed that administration of magnesium isoglycyrrhizinate significantly reduced the colonic fibrosis. Taken together, these results revealed the potency of magnesium isoglycyrrhizinate on the intestinal inflammation, by which points to the possible use of magnesium isoglycyrrhizinate for IBD therapy in clinical applications.

Background: Nutritional status, systemic inflammation, and coagulation mechanism are closely related to tumor progression. Herein, we examined the role of fibrinogen-to-albumin ratio index (FARI) in the prognosis of gastrointestinal stromal tumors (GISTs) and developed a novel nomogram predicting recurrence-free survival (RFS).Methods: We retrospectively analyzed data from 357 GIST patients admitted at the gastrointestinal surgery of the Beijing Hospital from January 2008 to January 2018 and underwent curative resection. FARI was calculated as fibrinogen level (g/L) /albumin level (g/L). The cutoff point of FARI was set using the point with the largest Youden index on the receiver operating characteristic curve with the 5-years recurrence-free survival as an endpoint. We used the Kaplan-Meier approach and multivariable Cox regression model to study the impact of FARI on recurrence-free survival. Finally, we developed a nomogram based on tumor size, location, mitotic index, and FARI to predict RFS. The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with the National Institute of Health (NIH) risk classification system.Results: The ROC curve revealed that the best cutoff point of the FARI was set as 0.08. The patients were classified into the FARI-high (≥0.08) and FARI-low (

Aging is accompanied by a disrupted information flow, which results from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders such as skeletal muscle wasting, or sarcopenia. To estimate the growing “disorderliness” of the aging muscle system, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Although the most prominent structural and functional alterations were observed in the oldest old mice (27-29 months), we found that the escalating network entropy reached an inflection point at old age (22-24 months). To probe the potential for restoration of molecular “order” and reversal of the sarcopenic phenotype, we overexpressed the longevity protein, α-Klotho. Klotho overexpression modulated genes representing all hallmarks of aging in both old and oldest-old mice. However, whereas Klotho improved strength in old mice, intervention failed to induce a benefit beyond the entropic tipping point.

Earlier reports suggest that limb venous distension evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) (i.e., venous distension reflex). Our recent report also shows that suction of arterially occluded limb evokes venous distension reflex. We postulate that the venous distension reflex contributes to autonomic responses to orthostatic stress. In this study, we hypothesized that orthostatic tolerance would be linked to the MSNA response seen with lower limb suction. Fifteen healthy subjects were tested in the supine position. Negative pressure (−100 mmHg) was applied on an arterially occluded lower limb for 2 min. MSNA from the peroneal nerve in the limb not exposed to suction, ECG, and BP (Finometer) was recorded throughout the study. Limb occlusion without suction was used as a control trial. In a separate visit, the individual’s orthostatic tolerance was assessed using a graded lower body negative pressure (LBNP) tolerance test. Mean arterial BP and MSNA (18.6 ± 1.9 to 23.6 ± 2.0 bursts/min) significantly (both P < 0.05) increased during limb suction. Orthostatic tolerance index positively correlated ( R = 0.636, P = 0.011) with the MSNA response seen with suction during occlusion. Since the venous distension reflex strength correlates with the level of orthostatic tolerance, we speculate that lower-limb venous distension reflex engagement increases the sympathetic responses during orthostatic challenge and serves to maintain BP with postural stress.

The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow‐up time was 57.5 months. The main outcome measure was disease‐free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M‐TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M‐NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M‐TTRG and M‐NLRG (p, Lymph node regression grade is an important prognostic factor in rectal cancer patients treated with neoadjuvant chemoradiotherapy and could refine the ypTNM staging system.

Objective: To establish an animal model consistent with the occurrence and development of non-alcoholic fatty liver disease (NAFLD) with which to assess the effects of a classical traditional Chinese medicine formula known as Dachaihu Decoction (DD) on NAFLD. Methods: Sixty rats were randomized into four groups: control, model, pioglitazone hydrochloride (PH) and DD in equal. NAFLD was produced via administration of a high-fat high-sugar diet for 16 weeks in all but the control group. From the 13th week, a solution of PH or DD prepared with water was delivered via intragastric administration to the PH and DD groups; the remaining two groups received an equivalent volume of distilled water. Twelve hours from the last administration, we selected eight rats from each group in random. After anesthetization, the abdominal aorta blood and liver tissues were collected. The morphological changes were observed and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FBG), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) were tested. Results: Compared with the control group, the levels of serum ALT, AST, TC, TG, LDL-C and FBG, and TGF-β1, TNF-α, TLR4, NF-кB in the model group all showed significant increases (P

There is growing evidence that highlighted the potential effects of CD147 in atherosclerosis, but the potential implication of CD147 in diagnosis and treatment of transient ischemic attack (TIA) and acute cerebral infarction (ACI) is still unclear. In this work, we investigated the serum level of CD147 in patients with TIA and ACI, and CD147 expression in atherosclerotic plaque. The result showed significantly increasing serum level of CD147 in patients with TIA and ACI, and increasing amount of CD147 in vulnerable plaque compared with that in migrating plaque. The serum level of CD147 was correlation with risk of stroke after an episode of TIA. These results together suggest a potential involvement of CD147 in the development and progression of TIA and ACI and CD147 as a potential biomarker for stroke prediction.

This study aimed to evaluate the prognostic value of the ratio of involved to uninvolved free light chain (rFLC) levels and lactic dehydrogenase (LDH) levels in the risk stratification of patients with multiple myeloma (MM).Clinical data of 283 patients with newly diagnosed MM were retrospectively analyzed.In the traditional chemotherapy group, patients with an rFLC100 had a better prognosis than those with an rFLC ≥ 100 (40 months versus 6 months, P = 0.022), as did patients with an LDH ≤ upper limit of normal (ULN) compared to those with an LDHULN (29 months versus 6 months, P = 0.023). In patients who underwent novel drug-combined therapy, no significant difference was observed between the rFLC100 group and the rFLC ≥ 100 group (54 months versus median not reached, P = 0.508). However, patients with an LDH ≤ ULN had a better prognosis than those with an LDHULN (60 months versus 21 months, P = 0.004). Using an rFLC ≥ 100 and an LDH ≥ ULN as adverse risk factors, patients were classified into 3 groups: group 1 (no adverse risk factors), group 2 (1 adverse risk factor) and group 3 (2 adverse risk factors). The median overall survival (OS) of groups 1, 2 and 3 was 52 months, 34 months and 15 months, respectively (P = 0.001).rFLC and LDH levels were sensitive prognostic factors in MM patients, combining them could improve the risk stratification and treatment choice of patients in clinical practice.

BACKGROUND AND OBJECTIVE Breast cancer is the leading cause of death in women worldwide. There are evidences that human cytomegalovirus (HCMV) infection is associated with several malignant tumors. This study aims to investigate the infection of human cytomegalovirus (HCMV) in a large sample of breast cancer patients, and conduct a correlation analysis of clinical and pathological factors, to provide evidence for whether HCMV infection is associated with breast cancer development, progression and metastasis. MATERIALS AND METHODS A total of 438 tissue samples (including breast cancer tissue, paracancerous tissue and sentinel lymph node [SLN] tissue) obtained from 146 patients who were diagnosed with breast cancer and intraoperatively underwent unilateral axillary SLN biopsy at the Affiliated Hospital of Qingdao University from June 2013 to June 2014 were included into this study. These tissue samples were divided into two groups: SLN positive group and SLN negative group. The clinical information is collated and numbered. Normal breast tissues of 40 patients with cyclomastopathy were taken as controls. The expressions of HCMV immediate-early (IE) and late antigen (LA) proteins of breast cancer tissues, paracancerous tissues, SLN tissues and normal breast tissues were analyzed by immunohistochemistry, and HCMV infection of the samples was graded according to the percentage of the positive cells, and HCMV IE2 mRNA expression was detected by reverse transcription polymerase chain reaction. The clinical data were collated and statistically analyzed. RESULTS HCMV IE and LA proteins were highly expressed in all breast cancer tissue samples. IE proteins were detected in 47.9% (70/146) of paracancerous tissue samples, and LA proteins were detected in 53.4% (78/146) of paracancerous tissue samples. IE and LA proteins were expressed in 92.6% of metastatic SLN samples (62/68) and in most of the tumor cells. Inflammatory cells in 60% (42/70) of non-metastatic samples were positive for HCMV. HCMV DNA was present in 100% of breast cancer tissue samples, 50% of paracancerous tissue samples, and 91% of metastatic SLN samples; but this was not present in HCMV negative and non-metastatic SLN samples. Differences in HCMV infection, and estrogen receptor-α, progesterone receptor, Elston classification, Ki67 percentage, Her-2 and Luminal type and other clinical indicators were not statistically significant. CONCLUSION HCMV infection is common in breast cancer tissues, paracancerous tissues and SLN tissues. The severity of HCMV infection varied markedly with tissue type. HCMV infection might be associated with metastasis and invasion of breast cancer. The expression of HCMV IE2 was associated to breast cancer and lymph node metastasis. The expression level of estrogen receptor-α was related to HCMV infection.

Minimally invasive surgery in knee arthroplasty can reduce postoperative pain and the rehabilitation period. The goal of this study was to explore the therapeutic effect of minimally invasive arthrolysis in post-traumatic knee stiffness.From March 2002 to March 2016, a prospective investigation was performed on seventy post-traumatic knee stiffness patients treated with minimally invasive knee arthrolysis or conventional knee arthrolysis. Curative effect was evaluated according to Judet's criteria. Operative time, incision length, blood loss, the angle of intraoperative release and the final postoperative joint mobility in two groups were compared using the student's t-test.The mean follow up time was 15.37 ± 4.93 months (ranged from 6 months to 2 years).The excellent and good rate was significantly higher in minimally invasive group (95.0%) than conventional arthrolysis group (73.33%) (P 0.05). Minimally invasive arthrolysis group had shorter operative time (29.38 ± 4.84 vs. 86.00 ± 9.77 min), smaller incision length (6.59 ± 0.86 vs. 20.47 ± 2.91 cm), less intraoperative blood loss (93.25 ± 15.26 vs. 473.33 ± 79.58 ml) and better postoperative final joint activity (104.75 ± 17.87° vs. 90.67 ± 19.64°) compared to conventional arthrolysis group (P 0.001).The findings suggest that minimally invasive knee arthrolysis is a much better option for the treatment of post-traumatic knee stiffness due to its advantages such as shorter operative time, little trauma, less blood loss and better postoperative final joint activity. Further studies with a long term of follow-up are wanted.

The study aim was to evaluate the association of the expression of serum microribonucleic acid-590 (miR-590) with the risk of lung squamous cell carcinoma (LUSC), clinicopathological staging and prognosis. A total of 237 patients with LUSC and 100 healthy volunteers (control group) were included in the study. Total RNA was extracted from the peripheral blood serum of the subjects, and the expression level of miR-590 was detected by reverse transcription real-time quantitative polymerase chain reaction. The baseline clinicopathological information of LUSC patients was evaluated, and the patients were followed up with the median follow-up of 47 months. Compared with that in the control group, the expression level of serum miR-590 in LUSC patients was significantly decreased [0.532 (0.367- 0.821) vs. 1.63 (0.893-1.347), P

To investigate the association between the severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery time after catheter ablation and identify predictors of cardiac function recovery after ablation.A total of 49 children underwent successful ablation (median 2.92 years). This study included 23 patients with mild cardiac dysfunction (left ventricular ejection fraction [LVEF]: 45% ≤ LVEF ≤ 55%), 15 with moderate (30% ≤ LVEF 45%), and 11 with severe (LVEF30%). The time for mean LVEF reaching 55% was 0.75, 3, and more than 12 months, respectively. The mean LVEF of children with severe cardiac dysfunction aged ≤6 years normalized within 12 months of follow-up (63.00% ± 1.41%). Mean LVEF of those aged more than 6 years did not normalize at 12 months of follow-up (38.67% ± 10.97%). LVEF recovery time was significantly different between these two age groups (median 11 months vs12 months, χPatients with higher LVDd Z scores and lower LVEF tend to have slower improvement in cardiac function after ablation. Patients with LVEF less than 30% and aged more than 6 years need more than 12 months to fully recover, and some might not even completely recover. Early catheter ablation is suggested once ventricular pre-excitation-led cardiac dysfunction is suspected.

Background: The purpose of this study was to reevaluate the efficacy of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) with the most recent published data and to identify subgroups who may be more likely to gain benefit from PCI. Methods: We searched PubMed, Embase, and Cochrane databases for randomized trials comparing PCI with non-PCI in NSCLC patients. We pooled the data of randomized controlled trials and compared brain metastasis (BM) and overall survival (OS) between PCI group and non-PCI group. Results: Seven studies including 1,462 patients were eligible for the current meta-analysis. Compared to non-PCI group, PCI group achieved decreased BM (RR = 0.37, 95% CI: 0.26–0.52) but similar OS (HR = 1.01, 95% CI: 0.87–1.22). In subgroup analyses of BM, PCI decreased BM for subgroups by pathology (squamous cell carcinoma or non-squamous cell carcinoma) and local treatment modality (surgery or no surgery). However, PCI failed to reduce BM for patients with poor performance status (WHO 2–3). The incidence of PCI related toxicities was low and PCI was well-tolerated by the majority of NSCLC. Low grade neurocognitive function (NCF) decline was reported in NAVLT study and greater deterioration in immediate and delayed recall was reported in RTOG 0214. No significant difference in quality of life (QOL) after PCI was reported. Conclusion: PCI reduces the incidence of BM except for patients with poor performance status. However, PCI fails to prolong OS significantly for NSCLC. An individual patient data meta-analysis may identify patients that could achieve OS prolongation with PCI.

Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.

Sevoflurane is a widely used obstetric general anesthetic, but the neurotoxic effects of late-pregnancy exposure to one minimum alveolar concentration ([MAC], 2.5%) of sevoflurane on offspring remain unclear. We investigated whether exposure to 2.5% sevoflurane during late pregnancy would affect offspring hippocampal neuronal development and neurocognitive function. On gestational day 18 (G18), rats were randomly treated with 2.5% sevoflurane in 50% oxygen for 1 (Sev × 1), 3 (Sev × 3), or 6 h (Sev × 6). The neuronal apoptosis rate and mature brain-derived neurotrophic factor (mBDNF) and postsynaptic density protein 95 (PSD-95) expression levels were measured in offspring hippocampi on postnatal day 1 (P1) and P35. Dendritic spine formation and cognitive function were examined on P35. The neuronal apoptosis rate was enhanced, and mBDNF and PSD-95 levels were reduced in the Sev × 3 and Sev × 6 groups on P1. mBDNF and PSD-95 levels were also decreased in the Sev × 6 group on P35. The error rate was elevated in the maze test, whereas dendritic spine density and long-term potentiation (LTP) were reduced in the Sev × 6 group on P35. To determine whether exposure to an enriched environment (EE) would ameliorate sevoflurane’s neurotoxic effects, offspring from another Sev × 6 group were exposed to either a standard environment (SE) or an EE. Lower error rates and greater dendritic spine densities and LTP were found in the Sev × 6 + EE vs. Sev × 6 + SE group. Collectively, we showed that exposing rats to 1 MAC sevoflurane for 3 h during late pregnancy increased neuronal apoptosis in neonates but did not impair neuronal development or cognitive function in juvenile rats, whereas a 6-h exposure impaired neuronal development and cognitive function in juvenile rats, effects that were attenuated by an EE.

This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated. Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment. The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance. Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.

// Jian Cui 1 , Lin Yang 2 , Lei Guo 2 , Yongfu Shao 1 , Dongfeng Tan 1 , Ni Li 3 and Haizeng Zhang 1 1 Department of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA 2 Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 3 National Office for Cancer Prevention and Control, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Correspondence to: Haizeng Zhang, email: // Ni Li, email: // Keywords : rectal cancer, neoadjuvant chemoradiotherapy, tumor regression grade, ypT stage, TNM staging system Received : August 08, 2016 Accepted : December 01, 2016 Published : January 17, 2017 Abstract Rectal cancer patients receiving neoadjuvant chemoradiotherapy (NCRT) are currently classified using the same Tumor-Node-Metastasis staging system as those patients without NCRT. We determined whether the combination of tumor treatment response (TRG) and ypT stage more accurately assesses primary tumors in rectal cancer after NCRT. We analyzed data from 329 rectal cancer patients treated with NCRT followed by radical resection. Cox proportional hazards models were used to evaluate the effects of different staging parameters on disease-free survival (DFS). ypN stage and TRG were independently associated with 3-year DFS, but ypT stage was not. We developed a new modified T stage classification metric (M-TTRG) that categorized patients into 5 subgroups based on ypT stage and TRG, with weighting by β-coefficients from multivariate analyses. The incidence of patients developing local or distant recurrence increased with increasing M-TTRG level. All five M-TTRG classes correlated with 3-year DFS. Improvement was seen in the model with M-TTRG classification compared with ypT stage, based on area under the curve after computing receiver operating characteristic curves. Our modified ypTNM staging system significantly improved prediction of 3-year DFS. This suggests TRG could complement ypT stage, and we propose the new M-TTRG metric could be used to better classify NCRT-treated patients, thereby improving treatment and assessing prognosis. The M-TTRG metric might be applicable to other types of cancer.

The effects of whole body heat stress on sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors remains unclear. We examined the muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate in 14 young healthy subjects during fatiguing isometric handgrip exercise, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed under normothermic and whole body heat stress (increase internal temperature ~0.6°C via a heating suit) conditions. Heat stress increased the resting MSNA and heart rate. Heat stress did not alter the mean blood pressure (MAP), heart rate, and MSNA responses (i.e., changes) to fatiguing exercise. During PECO, whole body heat stress accentuated the heart rate response [change (Δ) of 5.8 ± 1.5 to Δ10.0 ± 2.1 beats/min, P = 0.03], did not alter the MSNA response (Δ16.4 ± 2.8 to Δ17.3 ± 3.8 bursts/min, P = 0.74), and lowered the MAP response (Δ20 ± 2 to Δ12 ± 1 mmHg, P < 0.001). Under normothermic conditions, passive stretch during PECO evoked significant increases in MAP and MSNA (both P < 0.001). Of note, heat stress prevented the MAP and MSNA responses to stretch during PECO (both P > 0.05). These data suggest that whole body heat stress attenuates the pressor response due to metaboreceptor stimulation, and the sympathetic nerve response due to mechanoreceptor stimulation.

Background. Clinical studies on the efficacy of warm needle moxibustion to treat lumbar disc herniation are increasing, while studies on the assessment of its efficacy are still lacking. Objective. To assess the clinical effect of warm needle moxibustion on lumbar disc herniation. Methods. We searched relevant trials that compared warm needle moxibustion with other methods for lumbar disc herniation from 9 databases. Results. Warm needle moxibustion showed statistical significance efficiency rate compared with acupuncture and manipulation but had a similar rate with nonsteroidal anti-inflammatory drugs (NSAIDs). It showed a statistically significanty excellent rate when compared with acupuncture and manipulation but had a similar rate with NSAIDs. Regarding Japanese Orthopedic Association scores, it showed statistical significance with acupuncture and manipulation, but the rate was similar with Chinese medicine and NSAIDs. Regarding visual analog scale score, it demonstrated statistical significance when compared with acupuncture, manipulation, and NSAIDs but had a similar rate with Chinese medicine. Conclusion. Warm needle moxibustion is superior to acupuncture and manipulation in terms of efficiency rate, excellent rate, and controlling of pain for lumbar disc herniation, but it is similar when compared with NSAIDs and Chinese medicine.