Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study.

OBJECTIVES: Motion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects. MATERIALS AND METHODS: A total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined. RESULTS: Of note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021). CONCLUSIONS: Needleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.

Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy.

BACKGROUND & AIMS: The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS: We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS: We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION: Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

OBJECTIVES: Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. METHODS: This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. RESULTS: CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites (log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CONCLUSION: CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy.

Background and Aims: Rifaximin is effective in preventing and treating hepatic encephalopathy (HE). This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE (CHE). Methods: In this single-center, randomized, controlled, open-label study, CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test. Cirrhotic patients with CHE were recruited and randomly assigned to low-dose rifaximin 800 mg/day, high-dose rifaximin (1,200 mg/day), and control groups, and were treated for 8 weeks. The sickness impact profile (SIP) scale was used to evaluate the health-related quality of life (HRQOL) of patients. Forty patients were included in the study, 12 were assigned to the low-dose group, 14 to the high-dose group, and 14 patients to the control group. Results: The percentage of patients with CHE reversal was significantly higher in both the low-dose (41.67%, 5/12) and high-dose (57.14%, 8/14) groups than in the control group (7.14%, 1/14) at 8 weeks (p=0.037 and p=0.005, respectively). In addition, both doses of rifaximin resulted in significant improvement of the total SIP score compared with the control group. There were no significant differences in the CHE reversal rate, total SIP score improvement, and incidence of adverse event between the low-dose and high-dose groups (p>0.05). Conclusions: Low-dose rifaximin reverses CHE and improves HRQOL in cirrhotic patients with comparable effects and safety to high-dose rifaximin.

Sustained ameliorating effects and autonomic mechanisms of transcutaneous electrical acustimulation at ST36 in patients with chronic constipation.

Background and aims: The treatment of chronic constipation is still a great challenge in clinical practice. This study aimed to determine the efficacy and sustained effects of transcutaneous electrical acustimulation (TEA) at acupoint ST36 on the treatment of chronic constipation and explore possible underlying mechanisms. Methods: Forty-four patients with chronic constipation were recruited and randomly assigned to a TEA group or sham-TEA group. A bowel diary was recorded by the patients. The Patient Assessment of Constipation Symptom (PAC-SYM) and the Patient Assessment of Constipation Quality of Life (PAC-QoL) questionnaires were administered during each visit. Anal and rectal functions were evaluated with anorectal manometry. Autonomic functions were assessed by the special analysis of heart rate variability derived from the ECG recording. Results: Compared with sham-TEA, 2-week TEA treatment significantly increased the number of spontaneous bowel movements (SBMs) (5.64 ± 0.54 vs. 2.82 ± 0.36, P < 0.001) and lowered the total scores of PAC-SYM (0.90 ± 0.14 vs. 1.35 ± 0.13, P < 0.001) and PAC-QoL (0.89 ± 0.13 vs. 1.32 ± 0.14, P < 0.05). TEA improved symptoms, as reflected by a reduction in the straining (P < 0.001), the incomplete defecation (P < 0.05), the frequency of emergency drug use (P < 0.05), the days of abdominal distension (P < 0.01) and an increase in intestinal satisfaction (P < 0.01). Interestingly, the effects of TEA on the improvement of weekly SBMs sustained four weeks after the cessation of treatment (P < 0.001). Anorectal manometry indicated that 2-week treatment of TEA lowered the threshold of first sensation (P < 0.05), desire of defecation (P < 0.01) and maximum tolerable volume (P < 0.001) compared with sham-TEA group. TEA also significantly enhanced vagal activity, reflected by high-frequency band of heart rate variability, compared with sham-TEA (57.86 ± 1.83 vs. 48.51 ± 2.04, P < 0.01). Conclusion: TEA ameliorates constipation with sustained effects, which may be mediated via improvement of rectal sensitivity and enhancement of vagal activity. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR210004267].

Treatment of patients with Covid-19 with a high dose of ulinastatin.

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

The presence of NAFLD in nonobese subjects increased the risk of metabolic abnormalities than obese subjects without NAFLD: a population-based cross-sectional study.

BACKGROUND: With lifestyle modification and over-nutrition, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing annually. Here we aimed to assess the updated prevalence of NAFLD, and to evaluate the association of NAFLD with metabolic abnormalities according to gender, body mass index and age. METHODS: A population-based cross-sectional study was conducted in Shanghai from December 2016 to July 2017. With a three-stage stratified sampling strategy, 3,717 eligible participants were enrolled for the analysis. RESULTS: In total, 1,217 subjects (32.7%) had NAFLD. Among them, 400 (16.3%) of the nonobese and 817 (65.0%) of the obese subjects had NAFLD. The prevalence of NAFLD was increased according to the quartiles of age and waist circumference (WC) in the nonobese subjects. Females with nonobese NAFLD had 1.6-, 2.6-, 2.0-, 2.3- and 3.3-fold higher risks for metabolic syndrome, diabetes mellitus, hyperglycemia, hypertriglycerdemia (high TG) and low high-density lipoprotein cholesterol than obese subjects without NAFLD, respectively. Males had comparable metabolic profiles in both groups, except for a 2.0-fold higher risk of high TG in nonobese NAFLD subjects compared with obese subjects without NAFLD. More impressively, the homeostasis metabolic assessment insulin resistance index was comparable between the two groups. CONCLUSIONS: The increase of age and WC had significant impact on the risk of NAFLD in nonobese subjects. The presence of NAFLD in nonobese subjects increased the risk of metabolic diseases than obese subjects without NAFLD, especially in female.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

BACKGROUND AND AIMS: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. METHODS: In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. RESULTS: The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. CONCLUSION: Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications. CLINICAL TRIAL NUMBER: NCT02190357.

Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein evaluates liver function and predicts prognosis in liver cirrhosis.

OBJECTIVE: Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) is a novel glycobiomarker for evaluating liver fibrosis, but less is known about its role in liver cirrhosis (LC). This study aimed to investigate the utility of WFA+ -M2BP in evaluating liver function and predicting prognosis of cirrhotic patients. METHODS: We retrospectively included 197 patients with LC between 2013 and 2016. Serum WFA+ -M2BP and various biochemical parameters were measured in all patients. With a median follow-up of 23 months, liver-related complications and deaths of 160 patients were recorded. The accuracy of WFA+ -M2BP in evaluating liver function, predicting decompensation and mortality were measured by the receiver operating characteristic (ROC) curve, logistic and Cox's regression analyses, respectively. RESULTS: WFA+ -M2BP levels increased with elevated Child-Pugh classification, especially in patients with hepatitis B virus (HBV) infection. ROC analysis confirmed the high reliability of WFA+ -M2BP for the assessment of liver function using Child-Pugh classification. WFA+ -M2BP was also significantly positively correlated with the model for end-stage liver disease (MELD) score. Multivariate logistic regression analysis indicated WFA+ -M2BP as an independent predictor of clinical decompensation for compensated patients (odds ratio 11.958, 95% confidence interval [CI] 1.876-76.226, P = 0.009), and multivariate Cox's regression analysis verified WFA+ -M2BP as an independent risk factor for liver-related death in patients with HBV infection (hazards ratio 10.596, 95% CI 1.356-82.820, P = 0.024). CONCLUSION: Serum WFA+ -M2BP is a reliable predictor of liver function and prognosis in LC and could be incorporated into clinical surveillance strategies for LC patients, especially those with HBV infection.

New formula for predicting standard liver volume in Chinese adults.

AIM: To obtain a reference range of morphological indices and establish a formula to accurately predict standard liver volume (SLV) in Chinese adults. METHODS: Computed tomography (CT)-estimated total liver volume (CTLV) was determined in 369 Chinese adults. Age, sex, body weight, body height, body mass index, and body surface area (BSA) were recorded using CT. Total splenic volume, portal venous diameter (PVD), splenic venous diameter (SVD), and portal venous cross-sectional area (PVCSA) were also measured by CT. Stepwise multiple linear regression analysis was performed to evaluate the impact of each parameter on CTLV and to develop a new SLV formula. The accuracy of the new formula was compared with the existing formulas in a validation group. RESULTS: The average CTLV was 1205.41 ± 257.53 cm3 (range, 593.80-2250.10 cm3). The average of PVD, SVD and PVCSA was 9.34 ± 1.51 mm, 7.40 ± 1.31 mm and 173.22 ± 48.11 mm2, respectively. The CT-estimated splenic volume of healthy adults varied markedly (range, 46.60-2892.30 cm3). Sex, age, body height, body weight, body mass index, and BSA were significantly correlated with CTLV. BSA showed the strongest correlation (r = 0.546, P < 0.001), and was used to establish a new model for calculating SLV: SLV (cm3) = 758.259 × BSA (m2)-124.272 (R2 = 0.299, P < 0.001). This formula also predicted CTLV more accurately than the existing formulas, but overestimated CTLV in elderly subjects > 70 years of age, and underestimated liver volume when CTLV was > 1800 cm3. CONCLUSION: Our new BSA-based formula is more accurate than other formulas in estimating SLV in Chinese adults.

The evaluation of non-invasive multi-slice spiral computed tomography-based indices for the diagnosis and prognosis prediction of liver cirrhosis.

OBJECTIVE: This study aimed to evaluate easily available computed tomography (CT)-based parameters for assessing the presence and severity of cirrhosis and predicting complications in Chinese patients with cirrhosis. METHODS: CT-based morphological indices were determined in 167 patients with cirrhosis and 244 healthy volunteers. The correlation of morphological indices with Child-Pugh score and cirrhotic complications was analyzed using Spearman's correlation analysis. The area under the receiver operating characteristic curve (AUROC) was used to analyze the diagnostic performance of the indices. Sensitivity and specificity were determined. RESULTS: Patients with cirrhosis had a lower total liver volume (TLV) and a larger total splenic volume (SV) than healthy individuals. There was a significant difference in the portal venous diameter, splenic venous diameter and portal venous cross-sectional area between the two groups. A low TLV/SV ratio was strongly associated with liver cirrhosis; with a cut-off value of 4.27 for the diagnosis of cirrhosis TLV/SV had a sensitivity of 87.7% and a specificity of 84.9%, and AUROC of 0.921. Further analysis showed that TLV/SV was accurate in discriminating between mild and moderate/severe cirrhosis and could be used for predicting complications of cirrhosis. CONCLUSION: The easily available parameters of CT can accurately evaluate the severity of cirrhosis in Chinese patients.

Differentiation therapy of hepatocellular carcinoma by inhibiting the activity of AKT/GSK-3ß/ß-catenin axis and TGF-ß induced EMT with sophocarpine.

Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-ß.

Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of different doses of rifaximin in Chinese patients with liver cirrhosis. METHODS: This random prospective study included a screening visit, a 2-week treatment period and a subsequent 4-week observation phase. Patients with liver cirrhosis were randomly assigned to a low-dose rifaximin group, a high-dose rifaximin group and the control group in a ratio of 1:1:1. The low-dose and high-dose groups received 400 mg or 600 mg rifaximin per 12 h for 2 weeks, respectively. All other therapeutic strategies remained unchanged in the three groups as long as possible. RESULTS: In total, 60 patients with liver cirrhosis were screened and 43 of them met the eligibility criteria. After 2-week treatment serum endotoxin levels in the low-dose (1.1 ± 0.8 EU/mL) and high-dose rifaximin groups (1.0 ± 0.8 EU/mL) were significantly lower than that in the control group (2.5 ± 1.8 EU/mL), while no significant difference was found between the two rifaximin-treated groups. The effect of high-dose rifaximin on endotoxemia lasted for at least 4 weeks after drug withdrawal. A significant reduction in the abundance of the Veillonellaceae taxa and an increase in the abundance of Bacteroidaceae were shown after 2 weeks of rifaximin therapy. The incidence of adverse events and severe adverse events was similar among the three groups. CONCLUSION: Low-dose (800 mg/day) rifaximin could be analogous to high-dose (1200 mg/day) rifaximin to reduce the serum endotoxin level after 2 weeks of treatment.

New proposal for the serum ascites albumin gradient cut-off value in Chinese ascitic patients.

BACKGROUND: Serum ascites albumin gradient (SAAG) has been recognized as a reliable marker in the differential diagnosis of ascites. The etiological background of cirrhosis is rather different between western countries and eastern countries. The threshold of SAAG in Chinese ascitic patients has not been evaluated yet. The aim of this study was to define a new reasonable threshold of SAAG in Chinese ascitic patients. METHODS: Adult patients with ascites admitted to the Shanghai Changzheng Hospital from Jan 2004 to Jun 2010 were retrospectively analyzed. The diagnostic criteria for cirrhotic ascites are clinical manifestations, radiological features and esophageal-gastric varicosis, or histopathology. Serum was detected by chemical method using a commercial kit. We used receiver operating characteristic (ROC) analysis to achieve maximal sensitivity and specificity of SAAG. RESULTS: The mean value of SAAG in portal-hypertension-related ascites was significantly higher than that in the non-portal-hypertension-related ascites (21.15 ± 4.38 g/L vs 7.48 ± 3.64 g/L, P = 0.002). The SAAG cut-off value under 12.50 g/L predicted portal hypertension ascites with the sensitivity of 99.20%, specificity of 95.10% and accuracy of 97.65%. CONCLUSIONS: SAAG is useful to distinguish portal-hypertension-related ascites and non-portal-hypertension-related ascites, and 12.50 g/L might present as a more reasonable threshold in Chinese ascitic patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1602582638991860.