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Li-Hong Lu, Yu-Qing Song, Qi-Ming Wu, Zhao Wang, Yong-Fu Chen, Qian Dong, Xiao-Tao Han Department of Cardiology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qi-Ming WuDepartment of Cardiology, Beijing Ditan Hospital, Capital Medical University, No. 8 of Jingshun Street, Chaoyang District, Beijing, 100015, People’s Republic of ChinaTel +86 138 0100 9058Fax +86 10-84322988Email lulihong1954@163.comObjective: To improve our knowledge of cardiac manifestations caused by brucellosis through analyzing abnormal electrocardiograms of patients infected with brucella.Methods: A total of 108 cases were enrolled, and their electrocardiograms were analyzed and summarized retrospectively.Results: Among 108 cases, 77 (71.3%) had a normal electrocardiogram, and 31 (28.7%) had an abnormal electrocardiogram. There were 13 cases with nodal tachycardia (12%), 9 cases with sinus bradycardia (8%), 7 cases with sinus arrhythmia (6%), 8 cases with left ventricular high voltage (7%), 13 cases with abnormal ST segment and T wave (12%), 2 cases with abnormal Q wave (1.85%), 3 cases with complete right bundle branch block (2.78%), 3 cases with ventricular premature beat (2.78%), 1 case with left anterior fascicular block (0.9%), 1 case with first degree a-v block (0.9%), 1 case with QT internal prolongation (0.9%), 1 case with poor R wave progression (0.9%), and 1 case with short PR interval (0.9%).Conclusion: The cardiac manifestations of brucellosis were rare, but the mortality was high. Patients with abnormal electrocardiogram should have improved echocardiography in time. Early detection of the abnormal electrocardiogram could give a hint of cardiac damage to avoid the serious consequences.Keywords: brucella, brucellosis, ECG, manifestations, cardiac manifestations

Jie Mei,1,2,&ast; Xu-Qi Sun,3,&ast; Wen-Ping Lin,1,2,&ast; Shao-Hua Li,1,2 Liang-He Lu,1,2 Jing-Wen Zou,1,2 Wei Wei,1,2 Rong-Ping Guo1,2 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Ping Guo; Wei Wei Email guorp@sysucc.org.cn; weiwei@sysucc.org.cnBackground: Inflammatory response is related to cancer progression and patient survival. However, the value in predicting survival in hepatocellular carcinoma (HCC) patients who received anti-PD-1 therapy has not been elucidated. This study aimed to compare the predictive ability of inflammation-based scores for the prognosis of HCC patients after anti-PD-1 therapy.Methods: A total of 442 patients who received anti-PD-1 therapy were included in the study. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan–Meier survival curves, time-dependent receiver operating characteristic (ROC) and Harrell’s concordance index (C-index) analyses.Results: All the inflammation-based prognostic scores exhibited good discriminatory ability in overall survival (OS) (all P < 0.01), while the PNI score was a unique independent predictor for OS in multivariate analysis (hazard ratio, 1.770; confidence interval, 1.309– 2.393; P < 0.001). The areas under the ROC curves at 6, 12, 18 and 24 months and the C-index (0.65) demonstrated that the predictive accuracy of the PNI score was superior to that of the other inflammation-based scores.Conclusion: The PNI score is a discriminatory prognostic indicator for OS in HCC patients with anti-PD-1 therapy and is superior to the other inflammation-based prognostic scores in terms of predictive ability.Keywords: inflammation-based score, hepatocellular carcinoma, anti-PD-1 therapy, overall survival, prognostic nutritional index

Yong-Fa Zhang,1,2,* Liang-He Lu,3,4,* Chong Zhong,5,* Min-Shan Chen,3,4 Rong-Ping Guo,3,4 Lu Wang1,2 1Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 4State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 5Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaTel/Fax +8620-64175590Email cms024mm@163.comRong-Ping GuoDepartment of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of ChinaTel/Fax +8620-87342266Email guorp@sysucc.org.cnPurpose: This study aimed to evaluate the prognostic value of the lymphocyte-C-reactive protein ratio (LCR) score, a novel inflammation-based score based on lymphocytes and C-reactive protein, in hepatocellular carcinoma (HCC) patients treated with curative intent.Patients and Methods: A total of 1158 HCC patients undergoing surgical resection or radiofrequency ablation with curative intent were recruited from 3 different centres and divided into a primary cohort (n=716) and a validation cohort (n=442). Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS). The discriminatory accuracy of seven inflammation-based scores was compared by using the concordance index (C-index).Results: The LCR score differentiated HCC patients into two groups with distinct prognoses (1-, 3-, and 5-year OS rates and median OS: 92.9%, 81.9%, 73.3% and 99.2 months and 79.8%, 56.6%, 49.7% and 69.1 months; P< 0.001). Multivariate analysis showed that LCR score, AFP, ALBI score, tumour size, and TNM stage were independently associated with OS. When patients were stratified according to different disease states, the LCR score could still differentiate HCC patients into two groups with distinct prognoses (all P< 0.005). The LCR score demonstrated a markedly superior C-index of 0.621 compared with the other inflammation-based scores (0.503– 0.590). These findings were supported by the validation cohort.Conclusion: The preoperative LCR score is a novel, stable, and clinically feasible prognostic marker for patients with HCC, independent of liver function, tumour characteristics, and treatment allocation and is superior to other inflammation-based scores in terms of its prognostic ability.Keywords: hepatocellular carcinoma, resection, radiofrequency ablation, prognosis, LCR, inflammation-based score

Ming-Ta Hsieh,1– 3 Li-Hui Lu,2 Chi-Wei Lin,1,4 Yun-Wen Chen5 1Department of Family Medicine and Community Medicine, E-Da Hospital, Kaohsiung City, Taiwan; 2College of Law, National University of Kaohsiung, Kaohsiung City, Taiwan; 3Department of Nursing, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 4School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 5Pediatrician, Local Clinic, Kaohsiung City, TaiwanCorrespondence: Ming-Ta HsiehDepartment of Family Medicine and Community Medicine, E-Da Hospital, No. 1, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung City, 82445, TaiwanEmail kaplan210@yahoo.com.twBackground: The annual medical litigation rate has increased yearly since 1987 in Taiwan. Policy makers keep going medical legislation reforms. The effectiveness of legislation reforms to reduce malpractice litigation risk is uncertain.Objective: To determine whether medical legislation reform helps reduce the risk of medical litigation.Design, Setting, and Participants: This retrospective study used national data obtained from Ministry of Health and Welfare in Taiwan. The period analyzed was from 1987 to 2018. The annual medical litigation rate was determined, types of medical negligence litigation were compared, medical appraisal results were summarized, and the importance of medical legislation was identified.Interventions: After legislation reform vs before legislation reform.Measurements: The main outcome showed trends in medical dispute assessments over time by adjusting for the general population (per 1,  000,  000 people). We established 2004 and 2012 as the 2 cut-points for further analysis of medical appraisal results due to legislation reform.Results: With legislation reforms, the annual medical litigation rate decreased from 26.68 cases per million people in 2012 to 16.41 cases per million people in 2018. The annual medical litigation rate declined by approximately 38% from 2012 to 2018. Medical appraisal results were malpractice cases in 22.1% before Medical Care Act (2004 Reform) compared with 18.8% from 2004 to 2012 (odds ratio [OR], 0.82; 95% CI, 0.727– 0.924; p=0.001), and 6.4% after mediation system introduced in 2012 (odds ratio [OR], 0.243; 95% CI, 0.205– 0.288; p< 0.001).Conclusion: Medical legislation reform has reduced the risk of malpractice litigation over time.Keywords: medical malpractice, medical legislation reform, health policy

Yong-Fa Zhang,1,2,* Ming Shi,3,* Liang-He Lu,3 Lu Wang,1,2 Rong-Ping Guo3 1Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3The Department of Hepatobiliary Oncology of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of ChinaTel/Fax +8620-64175590Email cms024mm@163.comRong-Ping GuoDepartment of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of ChinaTel/Fax +8620-87342266Email guorp@sysucc.org.cnPurpose: It remains unknown which staging system is best in predicting the survival of patients with intermediate stage hepatocellular carcinoma (HCC). We aimed to investigate the performance of nine currently used HCC staging systems.Patients and Methods: Between 2005 and 2014, a large cohort of 880 consecutive patients with intermediate stage HCC and sufficient data for utilization in all staging systems were enrolled. The prognostic performance of each staging system was compared. Independent prognostic variables were also identified.Results: Multivariate analysis revealed that alkaline phosphatase (ALP), aspartate aminotransferase (AST), etiology, alpha-fetoprotein (AFP), Child-Pugh stage, tumor size, and tumor number were independent prognostic factors for survival. In the entire cohort, the Hong Kong Liver Cancer (HKLC) staging system was associated with the highest Harrell’s c-index and lowest Akaike information criterion value in comparison with other systems. In subgroup analysis according to treatment strategy, the HKLC staging system remained the best prognostic model in patients undergoing hepatic resection (n=222) or transarterial chemoembolization (n=658). Additional prognostic factors of AST, ALP, etiology, and AFP improved the discriminatory ability of HKLC.Conclusion: The HKLC staging system is stable and consistently the best prognostic model in all patients with intermediate-stage HCC and in patients subjected to different treatment strategies. Selecting an optimal staging system is helpful in improving the design of future clinical trials in intermediate stage HCC.Keywords: hepatocellular carcinoma, intermediate-stage, staging system, prognosis, overall survival, hepatic resection, transarterial chemoembolization

Jie Mei,1,2,* Shao-Hua Li,1,2,* Qi-Jiong Li,1,2,* Xu-Qi Sun,1,2 Liang-He Lu,1,2 Wen-Ping Lin,1,2 Lie Zheng,1,3 Min-Shan Chen,1,2 Ming Shi,1,2 Wei Wei,1,2 Rong-Ping Guo1,2 1Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Medical Imaging, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong-Ping Guo; Wei Wei Email guorp@sysucc.org.cn; weiwei@sysucc.org.cnBackground: Hepatic artery infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC), respectively. However, the combination of the two treatments has not been reported. In this study, we compared the efficacy of HAIC combined with anti-PD-1 immunotherapy (HAICAP) and HAIC in patients with advanced HCC.Methods: Between November 2018 and December 2019, advanced HCC patients that were treated with either HAICAP or HAIC were retrospectively recruited and reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.Results: As a result, 229 patients were included in this study. Patients were divided into HAICAP group (n = 81) and HAIC group (n = 148) accordingly. The follow-up time ranged from 1.0 to 21.6 months, with a median of 11.0 months. The median overall survival was 18.0 months in the HAICAP group and 14.6 months in the HAIC group (p = 0.018; HR = 0.62; 95% CI 0.34– 0.91). The median progression-free survival was 10.0 months in the HAICAP group and 5.6 months in the HAIC group (p = 0.006; HR = 0.65; 95% CI 0.43– 0.87). The disease control rate in overall response (83% vs 66%; p = 0.006) and intrahepatic response (85% vs 74%, respectively; p = 0.045) were higher in the HAICAP group than in the HAIC group.Conclusion: In comparison to HAIC, HAICAP was associated with a better treatment response and survival benefits for patients with advanced HCC.Keywords: hepatocellular carcinoma, hepatic artery infusion chemotherapy, programmed cell death protein-1, FOLFOX, combination therapy

Objective: The aim of the study was to assess the clinical features of women infected with the human immunodeficiency virus (HIV) using Holter monitoring., Methods: Thirty-five female patients infected with HIV using a Holter monitor at the Ditan Hospital were retrospectively analyzed., Results: In terms of basic rhythms, there were 30 cases of sinus rhythm, 27 cases of ventricular premature beat, 26 cases of supraventricular premature beat, 12 cases of mild reduction of HRV, 9 cases of normal heart rate variability (HRV), 8 cases of supraventricular tachycardia, 5 cases of abnormal ST-segment changes and 2 cases of sinus bradycardia 2 cases of paroxysmal atrial fibrillation 2 cases of junctional escape rhythm. There was only one case in each of the following ECG changes: persistent atrial fibrillation, sinus tachycardia, couplet supraventricular premature beats, accelerated idioventricular rhythm, sinoatrial block, second-degree Mobitz type I atrioventricular block, second-degree Mobitz type II atrioventricular block, complete right bundle branch block, T-wave abnormality, and significant reduction of HRV., Conclusion: The Holter monitor can show more changes in the electrocardiogram (ECG) of HIV-- positive patients, particularly significant ECG abnormalities, such as paroxysmal atrial fibrillation, and can direct early clinical treatment to serious adverse results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: To explore the efficacy of electroacupuncture (EA) based on the "ascending lucidity and descending turbidity" theory in patients with diabetic gastrointestinal dysfunction and its regulatory effect on gut microbiota., Methods: A total of 48 patients with diabetic gastrointestinal dysfunction were randomly divided into the EA group (24 cases, 3 cases dropped-off) and the control group (24 cases, no dropped off). Both groups received blood glucose control and basic symptomatic treatment. EA (15 Hz/100 Hz) was applied to Zhongwan (CV12), Tianshu (ST25), Zhongfu (LU1), bilateral Zhangmen (LR13), bilateral Taibai (SP3), bilateral Taiyuan (LU9), bilateral Zusanli (ST36), and bilateral Shangjuxu (ST37) in the EA group. Sham EA was applied to corresponding non-acupoints without electric stimulation in the control group. Both groups received treatment for 30 min per time, once daily, for a total of 5 treatments followed by a 2-day break, over a consecutive period of 2 weeks. Symptoms were evaluated by gastrointestinal symptom rating scale (GSRS) and gastroparesis cardinal symptom index (GCSI) before and after treatment, and 4 weeks after treatment. During the treatment period, fasting blood glucose levels were monitored daily. Stool samples were collected before and after treatment for 16S rDNA sequencing analysis to examine changes in gut microbiota., Results: Compared with the control group, GSRS and GCSI scores in the EA group were significantly decreased ( P <0.001) after treatment and at follow-up at the same time point, and compared with those before treatment, GSRS and GCSI scores in the EA group were significantly decreased after treatment and at follow-up ( P <0.001). After treatment, the 16S rDNA sequencing showed that at the phylum level, the ratio of Proteobacteria in the EA group was higher than that in the control group ( FDR <0.05). At the genus level, a total of 18 different gut microbiota were identified between the two groups. Compared to the control group, patients in the EA group showed a significant decrease in the abundance of Pseudomonas and Alkalibacter ( FDR <0.05), while the abundance of the remaining 16 gut microbiota was significantly increased ( FDR <0.05). Compared to the baseline, the EA group showed a significant up-regulation of Olsenella ( FDR <0.05) and a significant down-regulation of Pseudomonas ( FDR <0.05) after treatment., Conclusions: EA based on the "ascending lucidity and descending turbidity" theory can effectively improve the symptoms of patients with diabetic gastrointestinal dysfunction. EA can also affect the distribution of gut microbiota by up-regulating the levels of certain beneficial bacteria and suppressing pathogenic bacteria .

Objective: Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI)., Participants: Thirty-three military personnel with persistent headache post-mTBI., Main Outcome Measures: Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI., Results: Baseline COMPASS-31 versions were comparable and highly correlated ( r  = 0.72, p  < 0.001), they were moderately correlated at best to the NSI ( r  < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI ( r  = 0.39) score, but not to NSI ( r  = 0.28)., Conclusion: The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Research has found that service members (SMs) with mild traumatic brain injury (mTBI) and co-occurring bodily injuries endorse lower chronic postconcussive symptom severity than SMs with mTBI and no bodily injuries. Investigations were conducted with primarily post-9/11 war-era SMs with blast injuries. The current study explores these findings in a cohort of more heterogeneous and recently evaluated military SM. Possible reasons suggested for the earlier findings include SMs with bodily injuries report fewer postconcussive symptoms due to (1) focusing attention on extra-cranial injuries and associated pain; (2) receiving more interpersonal and medical support, lowering distress; (3) using analgesics such as morphine or opioids; or (4) experiencing delayed postconcussive symptoms. The current investigation evaluates each of these hypothesized reasons for the earlier findings and the generalizability of the findings to a more recent sample. Data were extracted from 165 SMs in a TBI repository at a U.S. military medical center. All participants reported a history of an mTBI, confirmed by a clinical interview to meet Veterans Affairs and Department of Defense criteria. Other bodily injuries received at the time of the mTBI were documented with the Abbreviated Injury Scale (AIS). Multiple regression models evaluated the ability of the four hypothesized mechanisms to predict postconcussive symptom severity, measured by the Neurobehavioral Symptom Inventory. SMs with bodily injuries ( n = 48) reported nonsignificantly lower postconcussive symptoms than SMs with no bodily injuries ( n = 117). The level of subjective pain was a determinant of postconcussive symptom severity among SMs with a history of mTBI, with or without associated bodily injuries. Social support was a weaker negative predictor of postconcussive symptoms among SMs with no associated bodily injuries., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Objective: Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis. Methods: We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University. Results: The mean and median age at onset were 47 and 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and some had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P ＜0.05). Conclusions: SMMN-FGT had a relatively good clinical prognosis, and even advanced patients could benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions were seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

Background: The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC-related radiological studies still focus on the prediction of VETC status., Purpose: This study aimed to build and compare VETC-MVI related models (clinical, radiomics, and deep learning) associated with recurrence-free survival of HCC patients., Study Type: Retrospective., Population: 398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22-80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40)., Field Strength/sequence: 3-T, pre-contrast T1-weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2-weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP)., Assessment: Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical-radiomic (CR) nomogram, deep learning model. The follow-up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow-up. Patients were followed up until December 31, 2022., Statistical Tests: Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier curves, log-rank test, C-index, and area under the curve (AUC). P < 0.05 was considered statistically significant., Results: The C-index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1-80 months)., Data Conclusion: MR deep learning model based on VETC and MVI provides a potential tool for survival assessment., Evidence Level: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood., Methods: Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B 1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups., Results: From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group ( P <0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group ( P< 0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group ( P <0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group ( P <0.05)., Conclusion: The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.

Introduction: Many service members (SMs) have been diagnosed with traumatic brain injury. Currently, military treatment facilities do not have access to established normative tables which can assist clinicians in gauging and comparing patient-reported symptoms. The aim of this study is to provide average scores for both the Neurobehavioral Symptom Inventory (NSI) and Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) for active duty SMs based upon varying demographic groups., Methods: Average scores were calculated for both the NSI and PCL-5 surveys from SMs who attended a military outpatient traumatic brain injury clinic. For this analysis, only the initial surveys for each SM were considered. The identifying demographics included age group, gender, grade, and race., Results: Four normative tables were created to show the average scores of both the NSI and PCL-5 surveys grouped by demographics. The tables are grouped by Age Group/Gender/Race and Grade/Gender/Race., Conclusion: Clinicians and healthcare administrators can use the scores reported in this study to determine where SM NSI or PCL-5 scores fall within the average for their demographic group., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Circular RNAs (circRNAs) play a role in sepsis-related autophagy. However, the role of circRNAs in autophagy after sepsis-induced cardiomyopathy (SICM) is unknown, so we explored the circRNA expression profiles associated with autophagy in an acute sepsis mouse model. At a dose of 10 mg/kg, mice were intraperitoneally administered with lipopolysaccharides. The myocardial tissue was harvested after 6 h for microarray analysis, qRT-PCR, and western blotting. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were evaluated, and a competing endogenous RNA network was constructed, to evaluate the role of circRNAs related to autophagy in SICM. In total, 1,735 differently expressed circRNAs were identified in the LPS-treated group, including 990 upregulated and 745 downregulated circRNAs. The expression level of the autophagy-specific protein p62 decreased, while the ratio of LC3 II to LC3 I increased. Additionally, 309 mRNAs and 187 circRNAs were correlated with autophagy in myocardial tissue after SICM. Of these, 179 circRNAs were predicted to function as "miRNA sponges". Some distinctive circRNAs and mRNAs found by ceRNA analysis might be involved in autophagy in SICM. These findings provide insights into circRNAs and identified new research targets that may be used to further explore the pathogenesis of SICM., (© 2023. The Author(s).)

Objective: To determine correspondence between the statistically derived 8-point reliable change index for the Neurobehavioral Symptom Inventory (NSI) against clinically significant item-level change in symptom severity from intake to discharge for mild traumatic brain injury (mTBI)., Setting: Brain Injury Rehabilitation Service at Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas., Patients: In total, 655 active-duty service members with a diagnosis of mTBI who received treatment and completed self-report measures between 2007 and 2020., Design: Observational retrospective analysis of outpatient clinical outcomes data., Main Measures: NSI total score change was used to divide patients into responder and nonresponders based on whether they met an 8-point decrease between intake and discharge. In addition, patients who had at least one NSI item that changed from a rating of 3 (severe) or 4 (very severe) at intake to a rating of 0 (none) or 1 (mild) at discharge were coded as an individual with significant item-level change., Results: Forty-five percent of the sample had significant item-level change and were classified as responders according to the reliable change method. Eight percent of the sample had significant item-level change but did not meet the 8-point reliable change threshold. Fifteen percent of the sample did not experience significant item-level change but were classified as responders according to reliable change. Thirty-one percent did not meet either method's criterion for change. Classification agreement between the reliable change and item-level change methods was 76%, which was statistically significant ( = 181.32, P < .001)., Conclusion: There is good correspondence between reliable change and item-level change on the NSI in this population. Reliable change is easily calculated and thus much more accessible than the item-level change method. There may be some situations where calculating item-level change may be helpful., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To systematically evaluate the efficacy and safety of acupuncture in the treatment of the vascular cognitive impairment (VCI) associated with cerebral small vessel disease (CSVD-VCI) and to provide a theoretical basis for clinical acupuncture treatment for CSVD-VCI., Method: Various databases, including China National Knowledge Infrastructure, Wanfang Data, Chinese Science and Technology Journal Database, Chinese BioMedical Literature Service System, PubMed, the Cochrane Library, and EBSCOhost, were searched for randomized controlled trials (RCTs) related to acupuncture treatment for CSVD-VCI. The quality of the included trials was evaluated, and a meta-analysis was conducted using the Review Manager 5.4 software., Results: Ten articles on RCTs were included, involving 761 patients, i.e., 381 in the acupuncture group and 380 in the control group. The meta-analysis results indicated that the use of acupuncture alone and acupuncture alongside other therapies for CSVD-VCI could improve the overall clinical response rate [odds ratio = 3.51, 95% confidence interval (CI) = (2.05, 6.00), P < 0.00001], increase the patients' Montreal Cognitive Assessment scores [mean difference (MD) = 3.33, 95%CI (2.98, 3.68), P < 0.00001], Mini-Mental State Examination scores [MD = 2.78, 95%CI (2.51, 3.06), P < 0.00001], and activities of daily living scores [MD = 6.30, 95%CI (4.22, 8.37), P < 0.00001], and shorten the latency of auditory evoked potential P300 [MD = -14.67, 95%CI (-19.54, -9.80), P < 0.00001]., Conclusion: Acupuncture alone and acupuncture alongside other therapies are superior to non-acupuncture-based therapies in the treatment of CSVD-VCI. However, due to the small number of relevant available articles and their general low quality, this conclusion may be biased. More clinical RCTs with a larger sample size and higher quality are needed to support this theory., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel., Method: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates., Results: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results., Conclusion: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.

The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and hyperuricemia is still undefined. Therefore, the aim of this study was to investigate the relationship between hyperuricemia and heavy metals. A total of 2447 participants (977 males and 1470 females) residing in southern Taiwan were enrolled, and levels of the following heavy metals were measured: lead in blood, and nickel, chromium, manganese, arsenic (As), copper, and cadmium in urine. Hyperuricemia was defined as a serum uric acid level greater than 7.0 mg/dL (416.5 μmol/L) in men and 6.0 mg/dL (357 μmol/L) in women. The participants were divided into two groups: those without hyperuricemia ( n = 1821; 74.4%) and those with hyperuricemia ( n = 626; 25.6%). Multivariate analysis showed that only high urine As (log per 1 μg/g creatinine; odds ratio, 1.965; 95% confidence interval, 1.449 to 2.664; p < 0.001), young age, male sex, high body mass index, high hemoglobin, high triglycerides, and low estimated glomerular filtration rate were significantly associated with hyperuricemia. In addition, the interactions between Pb × Cd ( p = 0.010), Ni × Cu ( p = 0.002), and Cr × Cd ( p = 0.001) on hyperuricemia were statistically significant. Increasing levels of Pb and Cr yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cd. Moreover, increasing levels of Ni yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cu. In conclusion, our results show that high urine As is associated with hyperuricemia, and some interactions of heavy metals on hyperuricemia are noted. We also found that young age, male sex, high BMI, high hemoglobin, high triglycerides, and low eGFR were significantly associated with hyperuricemia.

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar-capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The present study evaluated whether Grooved Pegboard (GPB), when used as a performance validity test (PVT), can incrementally predict psychiatric symptom report elevations beyond memory-apparent PVTs. Participants ( N  = 111) were military personnel and were predominantly White (84%), male (76%), with a mean age of 43 ( SD =  12) and having on average 16 years of education ( SD  = 2). Individuals with disorders potentially compromising motor dexterity were excluded. Participants were administered GPB, three memory-apparent PVTs (Medical Symptom Validity Test, Non-Verbal Medical Symptom Validity Test, Reliable Digit Span), and a symptom validity test (Personality Assessment Inventory Negative Impression Management [NIM]). Results from the three memory-apparent PVTs were entered into a model for predicting NIM, where failure of two or more PVTs was categorized as evidence of non-credible responding. Hierarchical regression revealed that non-dominant hand GPB T-score incrementally predicted NIM beyond memory-apparent PVTs ( F (2,108) = 16.30, p < .001; R 2 change = .05, β = -0.24, p < .01). In a second hierarchical regression, GPB performance was dichotomized into pass or fail, using T -score cutoffs (≤29 for either hand, ≤31 for both). Non-dominant hand GPB again predicted NIM beyond memory-apparent PVTs ( F (2,108) = 18.75, p <.001; R 2 change = .08, β = -0.28, p < .001). Results indicated that noncredible/failing GPB performance adds incremental value over memory-apparent PVTs in predicting psychiatric symptom report.

Purpose: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI)., Patients and Methods: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety., Results: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups., Conclusion: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Objective: This work was developed to compare the effects of transversus abdominis plane block (TAPB) and thoracic epidural anesthesia (TEA) mediated activation of inflammasome on postoperative medication, pain, and recovery in patients undergoing laparoscopic colorectal surgery. Then, the effects of two anesthesia methods on postoperative analgesia of patients were investigated and compared, aiming to provide reference for the selection of postoperative analgesia methods of laparoscopy., Patients and Methods: In this work, patients undergoing laparoscopic colorectal surgery were rolled into a TAPB group (30 patients) and a TEA group (30 patients). The blood pressure and stress indexes of the patients at different time points were observed and compared, and the doses of anesthetic drugs were recorded. Postoperative pain scores were evaluated, and postoperative recovery of the two groups was compared. Meanwhile, the peripheral venous bloods were extracted from the two groups before and after surgery for the determination of inflammasome proteins, and the detection results were compared., Results: Data showed that the dose of sufentanil in TEA group was notably inferior to that in TAPB group (p<0.05). The blood pressure indexes in the TEA group decreased remarkably (p<0.05), while their changes in the TAPB group were stable. The slower point heart rate (HR), lower mean arterial pressure (MAP), and lower levels of cortisol (Cor) and norepinephrine (NE) in the TEA group were found when compared with the TAPB group during the period from pneumoperitoneum establishment to post-ventilation. After pneumoperitoneum establishment, blood oxygen saturation (SpO2) in the TEA group was lower than that in the TAPB group at the same time point (p<0.05). The postoperative visual analog scales (VAS) score and numerical rating scale (NRS) score in TEA group were lower than those in TAPB group (p<0.05). After surgery, the protein level in TEA group was significantly lower than that in TAPB group (p<0.05)., Conclusions: In short, the activation of inflammasome mediated by TEA could reduce the anesthetic agents used after laparoscopic colorectal cancer surgery and reduce the surgical stress response. In addition, TEA exerted a little effect on early immunity, which was safe and feasible, contributing to postoperative analgesia and recovery. In addition, its application value in laparoscopic postoperative analgesia was higher than TAPB.

Objectives: To examine and categorize symptoms occurring within 60 s of vertebrobasilar-insufficiency (VBI) testing (left- and right-neck rotation) in individuals with persistent post-traumatic headache., Background: As part of routine clinical cervical screening in our patients, we found extended VBI testing often triggered additional symptoms. Therefore, we aimed to document the prevalence and precise symptoms occurring during each movement direction of this test and determine any demographic or baseline signs or symptoms associated with a positive test., Methods: A retrospective medical record review on military personnel receiving treatment for persistent post-traumatic headache was performed. Participants were grouped according to presence of non-headache related symptoms triggered during the tests. Frequency, onset, and symptom characteristics reported were categorized as potentially vascular and/or possible autonomic or cranial nerve in nature., Results: At least one symptom was reported by 81.3% of 123 patients. Of these, 54% reported symptoms in one and 46% in both directions of rotation, yielding 146 abnormal tests. Most reported symptoms were tear disruption (41%), altered ocular-motor-control (25%), and blepharospasm (16%). Enlisted individuals and those with altered baseline facial sensation were more likely to have a positive test., Conclusions: The majority reported symptoms not typical of VBI within 60 seconds of sustained neck rotation. Further study is needed to better understand the mechanisms and clinical relevance.

Objectives: To compare sub-occipital muscle pressure sub pain thresholds (PPTs) in individuals with persistent-post-traumatic-headache (PPTH) in relation to the presence or not of cranial nerve and/or autonomic symptoms reported during sustained neck rotation (SNR)., Background: Previously 81% of military service members with PPTH demonstrated symptoms with SNR up to 60 seconds. Of these, 54% reported symptoms in one (Uni-Symp) and 46% in both directions of rotation (Bi-Symp). Sub-occipital PPTs, in relation to SNR direction, were of interest., Methods: Retrospective review of records of 77 individuals, with PPTH with both SNR and PPTs. Average suboccipital and scalene PPTs were compared between Asymptomatic (n = 13), upon SNR testing, or Symptomatic (Uni-Symp, n = 32, Bi-Symp, n = 32), groups., Results: The Bi-Symp group had significantly reduced sub-occipital PPTs relative to the Asymptomatic group on both sides [p < 0.009] with no side-to-side differences in either group. The Uni-Symp group had significantly lower sub-occipital PPTs on the symptomatic SNR test direction compared to the asymptomatic side [t(31) = 3.37, p = 0.002]. There were no differences within or between groups in the scalene PPTs(p's > 0.08)., Conclusions: An upper cervical mechanical trigger of symptoms during SNR tests in some individuals with PPTH is possible. The direction of symptomatic SNR tests may indicate direction of guarded hypermobile dysfunction and direct treatment.

Rivers are often blocked by barriers to form different habitats, but it is not clear whether this change will affect the accumulation of N 2 O and CH 4 in rivers. Here, low barriers (less than 2 m, LB) increased N 2 O concentration by 1.13 times and CH 4 decreased by 0.118 times, while high barriers (higher than 2 m, less than 5 m high, HB) increased N 2 O concentration by 1.19 times and CH 4 by 2.76 times. Co-occurrence network analysis indicated LB and HB can promote the enrichment of Cyanobium and Chloroflexi , further limiting complete denitrification and increasing N 2 O accumulation. The LB promotes methanotrophs ( Methylocystis, Methylophilus , and Methylotenera ) to compete with denitrifiers ( Pseudomonas ) in water, and reduce CH 4 accumulation. While the HB can promote the methanotrophs to compete with nitrifiers ( Nitrosospira ) in sediment, thus reducing the consumption of CH 4 . LB and HB reduce river velocity, increase water depth, and reduce dissolved oxygen (DO), leading to enrichment of nirS -type denitrifiers and the increase of N 2 O concentration in water. Moreover, the HB reduces DO concentration and pmoA gene abundance in water, which can increase the accumulation of CH 4 . In light of the changes in the microbial community and variation in N 2 O and CH 4 accumulation, the impact of fragmented rivers on global greenhouse gas emissions merits further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xing, Li, Li, Lu and Li.)

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ&#95;(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ&#95;(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ&#95;(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ&#95;(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ&#95;(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Background: Immune-related adverse events (irAEs) are side effects that reflect the activation of patients' immune systems after treatment with immune checkpoint inhibitors (ICIs). However, there is no meta-analysis on the effect of early irAEs on patient survival. Thus, we assessed the association between early irAEs and the survival of patients treated with ICIs., Methods: PubMed, Embase, and Web of Science were searched from May 2010 to May 2020 for all the retrospective and prospective comparative studies to evaluate the hazard ratios (HRs) for death. A random-effects model was used to calculate the pooled HR for death, and heterogeneity was assessed using I² statistics. The main outcomes were overall survival (OS) and progression-free survival (PFS)., Results: A total of 11 reports with 2077 patients were included. A significant association was observed between early irAEs and a favorable clinical outcome. Patients with early irAEs had prolonged OS (HR: 0.62, 95% confidence interval (CI): 0.53-0.74, p < 0.001) and PFS (HR: 0.53, 95% CI: 0.41-0.66, p < 0.001) compared to those without; these results were confirmed using a sensitivity analysis. The irAE types, malignancy types, and sample size were correlated with patients' clinical outcomes., Conclusions: Early irAEs, especially cutaneous irAEs, correlated with a better clinical outcome in patients treated with ICIs.

Background/purpose: The treatment effects of Invisalign® are still obscure due to methodological limitations of previous studies. We introduced a method to comprehensively evaluate the dental and skeletal changes of Class II malocclusion treated non-extraction with Invisalign® and compare with the virtual simulation of ClinCheck® using digital models integrated into maxillofacial cone-beam computed tomography (CBCT)., Materials and Methods: The pretreatment (T1) and posttreatment (T2) scanned digital images of actual dentitions were integrated into maxillofacial CBCT images. To evaluate three-dimensional movement of maxillary teeth and change of mandible position, T1 and T2 digital model-integrated maxillofacial CBCT images were superimposed using voxel-based registrations of stable cranial base structures. To evaluate movement of mandibular teeth, model-integrated mandibular CBCT superimposition was registered on mandibular basal bone. To compare achieved and predicted tooth movements, the actual dental images and the virtual digital models created by ClinCheck® were registered on the T1 dentitions., Results: For simulated upper first molar (U6) distalization of more than 1 mm, treatment accuracy ranged from 31.1% to 40.1%, which was significantly less than virtual planning and previous reports. In unilateral Class II subjects, the amount of U6 distalization on the Class II side was not significantly different from contralateral side, indicating efficacy of sequential distalization was questionable. Those with favorable overjet correction showed evidence of condylar distraction., Conclusion: Digital model-integrated CBCT superimpositions reflected the actual treatment changes in comparison with the virtual simulation, and showed that ideal occlusion was not achieved in mild to moderate Class II adult patients treated non-extraction with Invisalign®., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

We aimed to determine the effect of vibration frequency and direction on upper-limb muscle activation using a handheld vibrator. We recruited 19 healthy participants who were instructed to hold a handheld vibrator in their dominant hand and maintain the elbow at 90° flexion, while vertical and horizontal vibrations were applied with frequencies of 15, 30, 45, and 60 Hz for 60 s each. Surface electromyography (EMG) measured the activities of the flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), extensor carpi ulnaris (ECU), extensor carpi radialis (ECR), biceps, triceps, and deltoid anterior muscles. EMG changes were evaluated as the difference in muscle activity between vibration and no-vibration (0 Hz) conditions. Muscle activity was induced under vibration conditions in both vertical and horizontal (p < 0.05) directions. At 45 Hz, FDS and FCR activities increased during horizontal vibrations, compared with those during vertical vibrations. ECU activity significantly increased under 15-Hz vertical vibrations compared with that during horizontal vibrations. Vibrations from the handheld vibrator significantly induced upper-limb muscle activity. The maximum muscle activations for FDS, ECR, ECU, biceps, and triceps were induced by 45-Hz horizontal vibration. The 60-Hz vertical and 30-Hz horizontal vibrations facilitated maximum muscle activations for the FCR and deltoid anterior, respectively.

Pre-frail older adults require appropriate exercise to enhance muscle strength as well as upper limb functionality. We developed a handheld vibrator and evaluated its effectiveness in enhancing muscle strength compared to conventional exercises among pre-frail community-dwelling older adults. Thirty-one pre-frail older adults (aged 75.5 ± 5.1 years) were recruited and randomly allocated to a vibration group (VG) and control group (CG). The VG underwent 20 minutes of vibration (frequency: 30 Hz, amplitude: 5 mm, horizontal vibration) using a handheld vibrator as well as 40 minutes of conventional exercise. The CG received 60 minutes of conventional exercise only. The primary outcome was muscle strength assessment (kg), and the secondary outcome included activities of daily living and instrumental activities of daily living scores. The comparisons between the outcome measures revealed no significant differences at the baseline level. Muscle strength of the dominant ( ß = 2.49, p = 0.002) and non-dominant ( ß = 1.89, p = 0.02) wrist flexion, brachioradialis ( ß = 3.8, p = 0.01), and biceps brachii ( ß = 3.02, p = 0.02) in the dominant upper limbs was significantly increased among the VG. The vibration intervention can enhance muscle strength in the upper limbs among pre-frail older adults., Competing Interests: The authors declare no conflicts of interest.

This study reported the cloning, expression, and characterization of a new salt-tolerant leucine dehydrogenase (PrLeuDH) from Pseudoalteromonas rubra DSM 6842. A codon-optimized 1038 bp gene encoding PrLeuDH was successfully expressed on pET-22b( +) in E. coli BL21(DE3). The purified recombinant PrLeuDH showed a single band of about 38.7 kDa on SDS-PAGE. It exhibited the maximum activity at 40 °C and pH 10.5, while kept high activities in the range of 25-45 °C and pH 9.5-12. The K m value and turnover number k cat for leucine of PrLeuDH were 2.23 ± 0.12 mM and 35.39 ± 0.05 s -1 , respectively, resulting in a catalytic efficiency k cat /K m of 15.87 s -1 /mM. Importantly, PrLeuDH remained 92.1 ± 2.67% active in the presence of 4.0 M NaCl. The study provides the first in-depth understanding of LeuDH from marine Pseudoalteromonas rubra, meanwhile the unique properties of high activity at low temperature and high salt tolerance make it a promising biocatalyst for the synthesis of non-protein amino acids and α-ketoacids under special conditions in pharmaceutical industry., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Using embedded performance validity (PVT) comparisons, Erdodi et al. suggested that Grooved Pegboard (GPB) T-score cutoffs for either hand ( ≤ 29) or both hands ( ≤ 31) could be used as additional embedded PVTs. The current study evaluated the relationship between these proposed cutoff scores and established PVTs (Medical Symptom Validity Test [MSVT]; Non-Verbal Medical Symptom Validity Test [NV-MSVT], and Reliable Digit Span [RDS])., Method: Participants (N = 178) were predominately Caucasian (84%) males (79%) with a mean age and education of 41 (SD = 11.7) and 15.8 years (SD = 2.3), respectively. Participants were stratified as "passing" or "failing" the GPBviaErdodi's proposed criteria. "Failures" on the MSVT, NV-MSVT, and RDS were based on conventional recommendations., Results: Moderate correlations between GPB classification and a condition of interest (COI; i.e. at least two failures on reference PVTs) were observed for dominant (χ 2 (1, n = 178) = 34.72, ϕ = .44, p < .001), non-dominant (χ 2 (1, n = 178) = 16.46, ϕ = .30, p = .001), and both hand conditions (χ 2 (1, n = 178) = 32.48, ϕ = .43, p < .001). Sensitivity, specificity, and predictive power were generally higher than Erdodi et al.'s initial findings., Conclusion: These findingsprovide supportfor the clinical utility of the GPB as an additional embedded PVT. More specifically, dominant and both hand cutoffs were found to be more robust measures ofnon-genuine performance in those without motor deficits. While promising, sensitivity continues to be low; therefore, it is ill-advised to use the GPB as a sole measure of -performance validity.

Objective: To characterize treatment responders and nonresponders as measured by the Neurobehavioral Symptom Inventory (NSI) in order to understand whether certain traits in our patient population would characterize favorable response., Setting: Brain Injury Rehabilitation Service at Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas., Patients: In total, 655 active duty military patients with a diagnosis of mild traumatic brain injury (mTBI) who received treatment between 2007 and 2020 and completed self-report measures as part of routine care., Design: Observational retrospective analysis of outpatient clinical outcomes data., Main Measures: The primary outcome measure was the NSI, divided into the responder and nonresponder groups. Responders were defined by reliable change in NSI total score (decrease of ≥8 points from intake to discharge)., Findings: Responders ( n = 395) reported a higher level of symptom burden at intake on the NSI. Women responded proportionally more (70%) than men (58%). After treatment, responders reported improvements on all measures evaluated while nonresponders reported no change or slightly worse symptoms. Logistic regression analysis showed that posttraumatic stress symptoms at intake decreased odds of favorable treatment response while satisfaction with social relationships increased odds of favorable treatment response., Conclusion: The results from this process improvement project suggested that posttraumatic symptoms warrant programmatic attention in TBI clinics while social relationships may be a protective factor that can be capitalized to enhance troop readiness. Systematic examination of these characteristics should be conducted on a larger population within the military health system., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Osteoarthritis (OA) is common in aged adults and can result in muscle weakness and function limitations in lower limbs. Knee OA affects the quality of life in the elderly. Technology-supported feedback to achieve lower impact on knee joints and individualized exercise could benefit elderly patients with knee OA. Herein, a computer-aided feedback rowing exercise system is proposed, and its effects on improving muscle strength, health conditions, and knee functions of older adults with mild knee OA were investigated., Methods: Thirty-eight older adults with mild knee OA and satisfying the American College of Rheumatology (ACR) clinical criteria participated in this randomized controlled clinical trial. Each subject was randomly assigned to a computer-aided rowing exercise (CRE) group (n = 20) or a control group (CON) (n = 18) that received regular resistance exercise programs two times per week for 12 weeks. Outcome measurements, including the Western Ontario and MacMaster Universities (WOMAC), muscle strength and functional fitness of the lower limbs, were evaluated before and after the intervention., Results: Participants' functional fitness in the CRE group exhibited significantly higher adjusted mean post-tests scores, including the WOMAC (p = 0.006), hip abductors strength (kg) (MD = 2.36 [1.28, 3.44], p = 5.67 × 10 -5 ), hip adductors strength (MD = 3.04 [1.38, 4.69], p = 0.001), hip flexors strength (MD = 4.01 [2.24, 5.78], p = 6.46 × 10 -5 ), hip extensors strength (MD = 2.88 [1.64, 4.12], p = 4.43 × 10 -5 ), knee flexors strength (MD = 2.03 [0.66, 3.41], p = 0.005), knee extensors strength (MD = 1.80 [0.65, 2.94], p = 0.003), and functional-reach (cm) (MD = 3.74 [0.68, 6.80], p = 0.018), with large effect sizes (η 2  = 0.17-0.42), than those in the CON group after the intervention., Conclusions: Older adults with knee OA in the CRE group exhibited superior muscle strength, health conditions, and functional fitness improvements after the 12-week computer-aided rowing exercise program than those receiving the conventional exercise approach., Trial Registration: The Institutional Review Board of the Taipei Medical University approved the study protocol (no. N201908020, 27/05/2020) and retrospectively registered at ClinicalTrials.gov (trial registry no. NCT04919486, 09/06/2021)., (© 2022. The Author(s).)

Objective: This study aims to compare the electrocardiogram (ECG) abnormalities and QT interval prolongation in 2,886 patients with viral hepatitis cirrhosis and 643 patients with alcoholic cirrhosis in order to understand the characteristics of ECG in patients with cirrhosis and provide information and evidence for clinical diagnosis and treatment., Methods: The ECG data of patients with viral hepatitis cirrhosis and alcoholic liver cirrhosis in the outpatients and inpatients of our hospital from August 2012 to July 2018 were reviewed. The ECG data were recorded, and the ECG report was issued by ECG experts to analyze the abnormal ECG and QT interval of patients in these two groups., Results: In the present study, 1,132 (39.22%) of the 2,886 patients with viral liver cirrhosis and 322 (50.08%) of the 643 patients with alcoholic liver cirrhosis had an abnormal ECG ( P  < 0.001). Among patients with QT prolongation, 388 patients had viral liver cirrhosis (13.44%) and 170 patients had alcoholic liver cirrhosis (26.44%, P  < 0.001)., Conclusion: The hemodynamics and electrophysiology of the myocardium are often changed in patients with cirrhosis, and ECG changes may also occur. QT interval prolongation is one of the most common electrophysiological abnormalities in patients with cirrhosis, and QT prolongation is more common in patients with alcoholic liver cirrhosis. Prolonged QT is associated with severe arrhythmia and sudden death and can warn of malignant arrhythmia and sudden death. Therefore, the routine detection of abnormal ECG and QT interval in patients with liver cirrhosis is of significant importance for preventing malignant events., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Li-Hong Lu et al.)

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA-miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA-mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM., (© 2022. The Author(s).)

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a "malignant" phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy., (© 2022. The Author(s).)

Background: We aimed to assess and compare kinetics and kinematic variables of bed turning ability using a mobility detection system in patients with and without chronic low back pain and to observe the impacts of the disease on bed turning kinetics and kinematics., Methods: Thirty-five patients with chronic low back pain were enrolled and compared to healthy controls (n = 34). Pain scores and disability level were assessed by Numeric Pain Rating Scale and the function questionnaires including Oswestry Disability Index and Roland Morris Disability Questionnaire. Bed turning ability was tested using the Mobile Detection System. Univariate and multivariate regression analysis were applied to compare the differences between groups., Findings: Patients with chronic low back pain had significantly lower turning over and back force/weight ratio (p < 0.001) than those healthy controls. Turning over time was significantly longer in patients with Numeric Rating Scale score 3 than in those with Numeric Rating Scale score 2 (p = 0.015). Turning over and back force were significantly higher in male patients and patients with higher BMI after adjusting BMI and sex, respectively (all p < 0.001). When turning back, chronic low back pain patients with Numeric Rating Scale scores of 3 had lower turning back force/weight ratio than those with Numeric Rating Scale scores of 2 (p = 0.014). Male patients had higher turning back force/weight ratio after adjusting pain score (p = 0.001)., Interpretation: The novel Mobility Detection System can provide more objective assessments of bed turning kinetics and kinematics in patients with chronic low back pain., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To evaluate the correlations between the Neurobehavioral Symptom Inventory (NSI) and other questionnaires commonly administered within military traumatic brain injury clinics., Setting: Military outpatient traumatic brain injury clinics., Participants: In total, 15,428 active duty service members who completed 24,162 NSI questionnaires between March 2009 and May 2020., Design: Observational retrospective analysis of questionnaires collected as part of standard clinical care., Main Measures: NSI, Post-Traumatic Stress Disorder Checklist for DSM-5 and Military Version, Patient Health Questionnaire (PHQ), Generalized Anxiety Disorder, Headache Impact Test (HIT-6), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Activities-Specific Balance Confidence Scale (ABC), Dizziness Handicap Inventory (DHI), Alcohol Use Disorders Identification Test (AUDIT), and the World Health Organization Quality of Life Instrument-Abbreviated Version. Only questionnaires completed on the same date as the NSI were examined., Results: The total NSI score was moderately to strongly correlated with all questionnaires except for the AUDIT. The strongest correlation was between the NSI Affective Score and the PHQ9 (r  = 0.86). The NSI Vestibular Score was moderately correlated with the ABC (r = -0.55) and strongly correlated with the DHI (r = 0.77). At the item level, the HIT-6 showed strong correlation with NSI headache (r = 0.80), the ISI was strongly correlated with NSI difficulty sleeping (r = 0.63), and the ESS was moderately correlated with NSI fatigue (r = 0.39)., Conclusion: Clinicians and healthcare administrators can use the correlations reported in this study to determine if questionnaires add incremental value for their clinic as well as to make more informed decisions regarding which questionnaires to administer., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)