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Enhanced recovery after surgery (ERAS) is a perioperative management protocol used to accelerate patient recovery. This study evaluated its benefits in patients with resectable esophageal cancer.This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After propensity score matching each group included 243 patients.There were significant differences in hospital length of stay after surgery (7.40 vs 11.17 days, P.001) and hospitalization cost (¥69380 vs ¥78075, P.001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs 7.16 days, P.001) and first bowel movement (2.87 vs 3.97 days, P.001) was significantly shorter in the ERAS group. However there was no significant difference in total postoperative complication morbidity (20.2% vs 25.1%, P = .193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P = .003), but there was no significant difference in occurrence of at least grade III complications between the 2 groups (12.3% vs 11.5%, P = .889).We demonstrated that ERAS could reduce hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore subgroup analyses revealed that ERAS was safe for older people (70 years old).

BACKGROUND: Thoracic endovascular repair (TEVAR) is considered the first-line therapy in the repair of acute complicated type B aortic dissection (AC-BAD). Given the difficulty of designing randomized trials in this surgical cohort, long-term outcome data is limited. This systematic review and meta-analysis provide a complete aggregation of reported long-term survival and freedom from reintervention of AC-BAD patients based on the existing literature. METHODS: Three databases were searched from date of database inception to January 2021. The relevant references were identified and baseline cohort characteristics, survival and freedom from reintervention were extracted. The primary endpoints were survival and freedom from reintervention, whilst secondary endpoints were post-operative outcomes such as cord ischemia and endoleak. Kaplan-Meier curves were digitized and aggregated as per established procedure. RESULTS: A total of 2,812 references were identified in the literature search for review, with 46 selected for inclusion. A total of 2,565 patients were identified, of which 1,920 (75%) were male. The mean age of the cohort was 59.8±5.8. Actuarial survival at 2, 4, 6 and 10 years was 87.5%, 83.2%, 78.5% and 69.7%, respectively. Freedom from all secondary reintervention at 2, 4, 6, 8 and 10 years was 74.7%, 69.1%, 65.7%, 63.9% and 60.9%, respectively. When accounting for study quality, actuarial survival at 2, 4, 6 and 8 years was 85.4%, 79.1%, 69.8% and 63.1%, respectively. Freedom from all secondary reintervention at 2, 4, 6 and 8 years was 73.2%, 67.6%, 63.7% (maintained), respectively. CONCLUSIONS: TEVAR is associated with promising long-term survival extended to 10 years, though rates of freedom from reintervention remain an ongoing point for improvement. Randomized controlled trials comparing endovascular with open repair in the setting of acute, complicated type B aortic dissection are needed.

Background Prenatal stress (PS) can cause brain retardation, reduce the learning and memory ability of the offspring and significantly increase the incidence of depression in offspring. Paeoniflorin (PF), a kind of monoterpenoid glycoside, is one of the main active ingredients of Chinese Medicine Paeonia lactiflora Pall, has anti-inflammation and potential neuroprotective effects. However, few reports have shown that the neuroprotective effects of PF are exerted through ameliorating Glutamate toxicity in vivo and in vitro. Methods Here, we used a prenatal restraint stress model and Glu-induced excitotoxic neurotoxicity in SH-SY5Y cells to study the effects of PF. Results Our results showed that PF can ameliorate learning and memory impairments and increases the density of hippocampal neurons, typical Golgi-positive pyramidal cells, and neuronal Neurogranin (Ng) expression in PS rat offspring. Furthermore, PF can significantly up-regulate the decrease of Glu-induced SH-SY5Y cell viability. At the same time, PF can significantly reduce apoptosis, ROS, NO levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. Besides, PF significantly increased the expression of Nrf2 and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active-caspase-3, and active-caspase-9. Conclusions Our results demonstrate that PF may be an effective treatment in preventing the development of PS-induced learning and memory impairment and have therapeutic potential in Glu-related neurological diseases.

Carrier transport was studied both numerically and experimentally using scanning photocurrent microscopy (SPCM) in two-dimensional (2D) transport structures, where the structure size in the third dimension is much smaller than the diffusion length and electrodes cover the whole terminal on both sides. Originally, one would expect that with increasing width in 2D transport structures, scanning photocurrent profiles will gradually deviate from those of the ideal one-dimensional (1D) transport structure. However, the scanning photocurrent simulation results surprisingly showed almost identical profiles from structures with different widths. In order to clarify this phenomenon, we observed the spatial distribution of carriers. The simulation results indicate that the integrated carrier distribution in the 2D transport structures with finite width can be well described by a simple-exponential-decay function with the carrier decay length as the fitting parameter, just like in the 1D transport structures. For ohmic-contact 2D transport structures, the feasibility of the fitting formula from our previous 1D analytical model was confirmed. On the other hand, the application of a simple-exponential-decay function in scanning photocurrent profiles for the diffusion length extraction in Schottky-contact 2D transport structures was also justified. Furthermore, our simulation results demonstrate that the scanning photocurrent profiles in the ohmic- or Schottky-contact three-dimensional (3D) transport structures with electrodes covering the whole terminal on both sides will reduce to those described by the corresponding 1D fitting formulae. Finally, experimental SPCM on a p-type InGaAs air-bridge two-terminal thin-film device was carried out. The measured photocurrent profiles can be well fitted by the specific fitting formula derived from our previous 1D analytical model and the extracted electron mobility-lifetime product of this thin-film device is 6.6 × 10–7 cm2·V−1. This study allows us to extract the minority carrier decay length and to obtain the mobility-lifetime product which can be used to evaluate the performance of 2D carrier transport devices.

Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. Results SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. Conclusions Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis. Graphic abstract

This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy.

Objective. To evaluate the stress status of fracture site caused by femoral neck shortening and to analyze the stress of fracture site and the implants from the finite element point of view. Methods. CT scan data of hip of a normal adult female were collected. Three-dimensional reconstruction MICs and related module function simulation was used to establish the postoperative shortening model of femoral neck fracture with Pauwels angle > 50 ° , which was treated with cannulated screws. The models were divided into four groups: normal femoral neck, shortening in 2.5 mm, shortening in 7.5 mm, and shortening in 12.5 mm. The finite element analysis software msc.nastran2012 was used, and the data of maximum stress and stress nephogram of fracture site and implants were carried out. Results. From normal femoral neck to shortening in 12.5 mm of the femoral neck, the maximum tensile stress increased gradually in the fracture site above the cannulated screws while compressive stress decreased gradually in the fracture site below the cannulated screws, and the maximum stress of the cannulated screws increased gradually with obvious stress concentration at the screw holes in the fracture site, and the peak value of stress concentration was about 179 MPa. Conclusion. The biomechanical environment of the fracture site changed by femoral neck shortening. With the increasing of femoral neck shortening, the stress of the fracture site and implants would be uneven; then, the stability of fracture site would become worse, and the possibility of implant sliding or even breakage would be increased.

Background and Aims Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with the invasion depth of early squamous cell neoplasia and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy for early squamous cell neoplasia where appropriate. Methods One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. Magnification endoscopy narrow-band imaging videos of squamous mucosa were labeled as dysplastic or normal according to their histology, and IPCL patterns were classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67,742 high-quality magnification endoscopy narrow-band images by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the Japanese Endoscopic Society IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Results Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1%, respectively. The CNN average F1 score was 94%, sensitivity 93.7%, and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. Conclusions We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable with an expert panel of endoscopists.

Hepatitis C virus (HCV) is responsible for a variety of human life-threatening diseases, which include liver cirrhosis, chronic hepatitis, fibrosis and hepatocellular carcinoma (HCC) . Computational study of protein-protein interactions between human and HCV could boost the findings of antiviral drugs in HCV therapy and might optimize the treatment procedures for HCV infections. In this analysis, we constructed a prediction model for protein-protein interactions between HCV and human by incorporating the features generated by pseudo amino acid compositions, which were then carried out at two levels: categories and features. In brief, extra-tree was initially used for feature selection while SVM was then used to build the classification model. After that, the most suitable models for each category and each feature were selected by comparing with the three ensemble learning algorithms, that is, Random Forest, Adaboost, and Xgboost. According to our results, profile-based features were more suitable for building predictive models among the four categories. AUC value of the model constructed by Xgboost algorithm on independent data set could reach 92.66%. Moreover, Distance-based Residue, Physicochemical Distance Transformation and Profile-based Physicochemical Distance Transformation performed much better among the 17 features. AUC value of the Adaboost classifier constructed by Profile-based Physicochemical Distance Transformation on the independent dataset achieved 93.74%. Taken together, we proposed a better model with improved prediction capacity for protein-protein interactions between human and HCV in this study, which could provide practical reference for further experimental investigation into HCV-related diseases in future.Communicated by Ramaswamy H. Sarma.

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

Background The superior facet arthroplasty is important for intervertebral foramen microscopy. To our knowledge, there is no study about the postoperative biomechanics of adjacent L4/L5 segments after different methods of S1 superior facet arthroplasty. To evaluate the effect of S1 superior facet arthroplasty on lumbar range of motion and disc stress of adjacent segment (L4/L5) under the intervertebral foraminoplasty. Methods Eight finite element models (FEMs) of lumbosacral vertebrae (L4/S) had been established and validated. The S1 superior facet arthroplasty was simulated with different methods. Then, the models were imported into Nastran software after optimization; 500 N preload was imposed on the L4 superior endplate, and 10 N⋅m was given to simulate flexion, extension, lateral flexion and rotation. The range of motion (ROM) and intervertebral disc stress of the L4-L5 spine were recorded. Results The ROM and disc stress of L4/L5 increased with the increasing of the proportions of S1 superior facet arthroplasty. Compared with the normal model, the ROM of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 2/5 from the apex to the base. The disc stress of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 1/5 from the apex to the base. Conclusion In this study, the ROM and disc stress of L4/L5 were affected by the unilateral S1 superior facet arthroplasty. It is suggested that the forming range from the ventral to the dorsal should be less than 3/5 of the S1 upper facet joint. It is not recommended to form from apex to base. Level of evidence Level IV

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P P P = 0.001) than survivors did. Kaplan–Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Introduction: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. Methods: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. Results: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. Conclusion: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count.

Background: CRF01_AE and CRF07_BC are the two major HIV-1 virus strains circulating in China. The proportion of dominant subtypes (CRF01_AE and CRF07_BC) among MSM in Jiangsu province was over 80%. A large number of URFs have been found in China in recent years. Objective: This study aimed to report on novel HIV-1 recombinants. Method: We constructed Phylogenetic trees using the maximum likelihood (ML) method with 1000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination breakpoints using SimPlot 3.5.1. Results: We identified a novel, second-generation HIV-1 recombinant (JS020202) between CRF01_ AE and CRF07_BC. The analysis of near full-length genome (NFLG) showed there were at least 8 breakpoints in the virus, which differed from any previously identified CRF and URF around the world. Conclusion: Novel diverse CRF01_AE/07_BC suggested the complexity trends of HIV-1 genetics. The emergency situation of diverse recombinant strains should be monitored continuously.

INTRODUCTION Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch. METHODS ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

To combat severe soil desertification and sandstorms, the application of appropriate hydrogels to dry land/desert is a promising solution to advance sustainable water irrigation and retention, and even realize “intelligent” agriculture. To this end, the development of a hydrogel with stable monitoring functions and good mechanical properties to maintain the swelling capability under soil would be significant for “intelligent” agriculture applications. Herein, we report a robust bio-based hydrogel with excellent mechanical properties and unique fluorescence performance for monitoring irrigation applications. This bio-hydrogel possesses a double cross-linked interpenetrating supramolecular network in a bacterial cellulose (BC) porous matrix, which provides its high tensile/compressive strength (∼0.96/1.3 MPa) and excellent Young's modulus (∼6.67 MPa, vs. 0.01–1.0 MPa for reported agricultural hydrogels), as well as high strength retention after experiencing repeated swelling/drying and long-term compressive processes. Furthermore, the hydrogel displays unique non-traditional fluorescence with excellent stability even under extreme environmental conditions, such as high/low temperature and various organic solvents. The excellent fluorescence characteristics offer the potential to realize “visualized” agricultural irrigation. This study not only provides a distinctive bio-based hydrogel with broadened applications, but also presents new insight to promote the development of sustainable agriculture.

Despite HCV cure, patients remain at risk for HCC, but risk factor data for HCC following SVR are limited for Asian patients. To address this gap, we analyzed 5814 patients (5646 SVR, 168 non-SVR) from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) who did not have HCC or a history of HCC at baseline (pre-DAA treatment) and did not develop HCC within 6 months of baseline. To assess the effect of SVR on HCC incidence, we used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and baseline AFP] to balance the SVR and non-SVR groups. In the PSM cohort (160 non-SVR and 612 SVR), the HCC incidence rate per 100 person years was higher in the non-SVR compared to the SVR group (5.26 vs. 1.94, p

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.

Purpose Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. Patients and Methods The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. Results We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.

We conducted a multicenter retrospective cohort study of metabolic dysfunction‐associated hepatocellular carcinoma. In this cohort, cirrhosis was not associated with poorer survival, while history of liver imaging was., Metabolic‐associated fatty liver disease (MAFLD) is a major cause of liver‐related complications, including hepatocellular carcinoma (HCC). While MAFLD‐related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD‐related HCC in this setting is limited. Here, we characterize MAFLD‐related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD‐related HCC. MAFLD was defined based on the presence of race‐adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan‐Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12 months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer‐related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD‐related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD‐related HCC was disappointingly low in a multicenter cohort.

Background: Data from the USA suggest that chronic hepatitis B (CHB) patients have aged in the past decade. However, the burden of nonliver comorbidities has not been well characterized in Taiwan, where CHB is very prevalent. Aim: Our study examined this issue as it presented between 2001 and 2011 in Taiwan. Methods: This study identified adult patients (≥18 years) who were diagnosed with CHB in 2001, 2006, and 2011, from the Taiwan National Health Insurance Research Database (NHIRD). Changes in demographic characteristics, prevalence of nonliver comorbidities, and medication usage over the decade were examined. Non-CHB controls were adults without CHB diagnosis from the Longitudinal Health Insurance Database 2000 (LHID2000). Results: A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The mean age significantly advanced from 45.4 to 52.3 years over the decade (p < 0.001). The prevalence of comorbidities, including diabetes mellitus, hypertension, stroke, chronic kidney disease, and bone fracture, significantly increased between 2001 and 2011 (all p < 0.001), as so were medication usage (all p < 0.001). Moreover, within each study period, compared to non-CHB controls, CHB patients were also older and more likely to have metabolic and cardiovascular comorbidities (all p < 0.001). In addition, the annual nonliver mortality in the CHB population significantly increased from 2001 to 2011. Conclusions: Over a decade, the CHB population in Taiwan has aged with a higher nonliver comorbidity burden and increasing nonliver mortality. These findings may provide information to care providers in the monitoring and management of CHB patients.

Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality.This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed.Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratiolsqb;HR], 1.26; 95% confidence intervallsqb;CI], 1.20 to 1.33; P.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database.

With increasing numbers of patients surviving acute intoxication phase, long-term complication after paraquat intoxication is a topic worth exploring, such as osteonecrosis (ON) of femoral head. We reviewed 86 paraquat-intoxicated survivors between 2000 and 2012 in Chang Gung Memorial Hospital, a 3700-bed tertiary hospital in Taiwan. With all the patients underwent same detoxification protocol in the acute stage, 17.4% of paraquat poisoning survivors developed ON of femoral head requiring surgery during follow up. Most of ON episodes occurred within 2 to 4 years after paraquat intoxication and then plateau after 6 years. ON patients exhibited higher SOFA scores than non-ON patients (2.80 ± 2.14 vs. 1.76 ± 1.52, p = 0.028). Furthermore, AKIN scores are also higher in the ON patients than non-ON patients (0.87 ± 1.13 vs. 0.38 ± 0.74, p = 0.040). Multivariate logistic regression showed higher AKIN score and higher partial pressure of carbon dioxide in the blood 48 hours after admission significantly predicted ON of femoral head after paraquat intoxication (p = 0.002 and p = 0.006 respectively). Larger studies with longer follow-up durations are warranted to confirm our finding.

Background and aim Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been shown to reduce incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This systematic review aims to evaluate the magnitude, change over time, and prediction of residual HCC risks in CHB patients treated with ETV/TDF therapy. Methods Available literature was systematically reviewed through searches of PubMed and EMBASE databases from January 1, 2006 to September 1, 2019, to identify cohort studies that reported HCC incidence in CHB patients during ETV/TDF therapy. Studies were screened by title and abstract and then evaluated for eligibility in terms of full text. Results We identified 141 studies for full-text review, and 34 were eligible for analysis. From 19 studies with data separated by cirrhosis status, the 5-year cumulative incidence of HCC was 0.5-6.9% in patients without cirrhosis, 4.5-21.6% in compensated cirrhosis, and 36.3-46.5% in decompensated cirrhosis. All four studies that addressed temporal changes in HCC risks consistently found the incidence rate decreased over time in patients with cirrhosis, although the findings were inconsistent in patients without cirrhosis. Six predictive scores were developed and validated to predict incident HCC during ETV/TDF therapy in CHB patients. Common scoring variables included age, sex, cirrhosis (fibrosis grade), and hepatic function. Conflicting results were reported in seven individual studies and two meta-analyses that compared ETV versus TDF. Conclusions The residual risk of HCC remains during ETV/TDF treatment in CHB patients with cirrhosis but declines over time. Risk stratification is attainable by validated predictive scores.

Glioblastoma (GBM) is the most common and malignant primary adult brain tumor. Current care includes surgical resection, radiation, and chemotherapy. Recent clinical trials for GBM have demonstrated extended survival using interventions such as tumor vaccines or tumor-treating fields. However, prognosis generally remains poor, with expected survival of 20 months after randomization. Chemokine-based immunotherapy utilizing CCL21 locally recruits lymphocytes and dendritic cells to enhance host antitumor response. Here, we report a preliminary study utilizing CPZ-vault nanoparticles as a vehicle to package, protect, and steadily deliver therapy to optimize CCL21 therapy in a murine flank model of GBM. GL261 cells were subcutaneously injected into the left flank of eight-week-old female C57BL/6 mice. Mice were treated with intratumoral injections of either: (1) CCL21-packaged vault nanoparticles (CPZ-CCL21), (2) free recombinant CCL21 chemokine empty vault nanoparticles, (3) empty vault nanoparticles, or 4) PBS. The results of this study showed that CCL21-packaged vault nanoparticle injections can decrease the tumor volume in vivo. Additionally, this study showed mice injected with CCL21-packaged vault nanoparticle had the smallest average tumor volume and remained the only treatment group with a negative percent change in tumor volume. This preliminary study establishes vault nanoparticles as a feasible vehicle to increase drug delivery and immune response in a flank murine model of GBM. Future animal studies involving an intracranial orthotopic tumor model are required to fully evaluate the potential for CCL21-packaged vault nanoparticles as a strategy to bypass the blood brain barrier, enhance intracranial immune activity, and improve intracranial tumor control and survival.

Early epoxy vitrimers in the literature rely on an inequivalent epoxy/anhydride stoichiometry and a large amount of catalyst to achieve a decent transesterification rate within the crosslinked netw...

Purpose A consensus about the pathogenesis of torus palatinus (TP) in patients receiving dialysis still eludes the scientific community. This prospective observational study investigated the epidemiology of TP in peritoneal dialysis and hemodialysis patients and analyzed the influences of multiple pathogenic factors such as mineral and bone disorders, genetic, environmental or nutritional triggers, progression of age, heredity, climatologic or biomechanical causes, and hyperparathyroidism on the formation of TP. Methods Between 2013 and 2016, a total of 575 chronic dialysis patients (441 on hemodialysis and 134 on peritoneal dialysis) were recruited from Chang Gung Memorial Hospital, Taiwan. Patients were stratified into two groups based on the presence (n = 179) or absence (n = 396) of TP. Demographic, oral examination, laboratory, and dialysis data were collected for analysis. Student's t-test was used to analyze the quantitative variables and Chi-square or Fisher's exact test for categorical variables. Univariate binary logistic regression analysis was conducted to determine the predictors for TP and multivariate binary logistic regression analysis to identify significant associated factors. Results The prevalence of TP in dialysis patients in this study was 31.1% (28.3% for hemodialysis and 40.3% for peritoneal dialysis). Patients with TP were younger (54.6 ± 13.4 versus 58.9 ± 14.7 years, P = 0.001) and mostly female (60.3 versus 41.2%, P < 0.001). Most TP cases (55.3%) were small in size (

Background Radioresistance of some non-small cell lung cancer (NSCLC) types increases the risk of recurrence or metastasis in afflicted patients, following radiotherapy. As such, further improvements to NSCLC radiotherapy are needed. The expression of oncogene TP53-regulated inhibitor of apoptosis 1 (TRIAP1) in NSCLC is increased following irradiation. Furthermore, gene set enrichment analysis (GSEA) has suggested that TRIAP1 might be involved in maintaining redox homeostasis. This in turn might enhance cell radioresistance. Methods In this study we irradiated human NSCLC cell lines (A549 and H460), while knocking down TRIAP1, to determine whether a disrupted redox homeostasis could attenuate radioresistance. Results Irradiation notably increased both mRNA and protein levels of TRIAP1. In addition, TRIAP1 knockdown decreased the expression of several antioxidant proteins, including thioredoxin-related transmembrane protein (TMX) 1, TMX2, thioredoxin (TXN), glutaredoxin (GLRX) 2, GLRX3, peroxiredoxin (PRDX) 3, PRDX4, and PRDX6 in A549 and H460 cells. In addition, silencing TRIAP1 impaired the radiation-induced increase of the aforementioned proteins. Continuing along this line, we observed a radiation-induced reduction of cell viability and invasion, as well as increased apoptosis and intracellular reactive oxygen species following TRIAP1 knockdown. Conclusions In summary, we identified TRIAP1 as a key contributor to the radioresistance of NSCLC by maintaining redox homeostasis.

The esophageal gland duct may serve as a pathway for the spread of early esophageal squamous cell neoplasia (ESCN) to a deeper layer. Deep intraductal tumor spreading cannot be completely eradicated by ablation therapy. However, the risk factors of ductal involvement (DI) in patients with ESCNs have yet to be investigated. We consecutively enrolled 160 early ESCNs, which were treated with endoscopic submucosal dissection. The resected specimens were reviewed for the number, morphology, resected margin, distribution and extension level of DI, which were then correlated to clinical factors. A total of 317 DIs (median:3, range 1–40 per-lesion) in 61 lesions (38.1%) were identified. Of these lesions, 14 have DIs maximally extended to the level of lamina propria mucosa, 17 to muscularis mucosae, and 30 to the submucosa. Multivariate logistic regression analysis showed that tumors located in the upper esophagus (OR = 2.93, 95% CI, 1.02–8.42), large tumor circumferential extension (OR = 5.39, 95% CI, 1.06–27.47), deep tumor invasion depth (OR = 4.12, 95% CI, 1.81–9.33) and numerous Lugol-voiding lesions in background esophageal mucosa (OR = 2.65, 95% CI, 1.10–6.37) were risk factors for DI. The maximally extended level of ducts involved were significantly correlated with the cancer invasion depth (P

Background Cure rates of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared with HCV/non-HCC patients. Methods Using data from the Real-World Evidence from the Asia Liver Consortium (REAL-C) registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin levels to evaluate DAA treatment outcomes in a large population of HCV/HCC compared with HCV/non-HCC patients. Results We included 6081 patients (HCC, n = 465; non-HCC, n = 5 616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs 93.7%; P = .03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR, 0.28; P = .01) when compared with non-HCC. Conclusions Active HCC but not inactive HCC was independently associated with lower SVR compared with non-HCC patients undergoing DAA therapy, although cure rate was still relatively high (85%) in active HCC patients.

This study aims to examine ionoregulatory parameters during exercise and cortisol elevation in common carp fed different food rations. Fish subjected to two different feeding regimes (0.5 or 3.0% body mass (BM) daily) received no implant or an intraperitoneal cortisol implant (250 mg/kg BM) or sham, and were monitored over a 168-h post-implant (PI) period under resting, low aerobic swimming or exhaustive swimming conditions. Plasma osmolality was maintained at relatively stable levels without much influence of feeding, swimming or cortisol, especially in low feeding groups. Nevertheless, a transient hyponatremia was observed in all low feeding fish implanted with cortisol. The hyponatremia was more pronounced in fish swum to exhaustion but even in this group, Na+ levels returned to control levels as cortisol levels recovered (168 h-PI). Cortisol-implanted fish also had lower plasma Cl- levels, and this loss of plasma Cl- was more prominent in fish fed a high ration during exhaustive swimming (recovered at 168 h-PI). Cortisol stimulated branchial NKA and H+ ATPase activities, especially in high ration fish. In contrast, low ration fish upregulated kidney NKA and H+ ATPase activities when experiencing elevated levels of cortisol. In conclusion, low feeding fish experience an ionoregulatory disturbance in response to cortisol implantation especially when swum to exhaustion in contrast to high feeding fish.

Grain size composition, crack pattern, and crack length have a significant influence on the crack characteristics, mechanical characteristics, and acoustic emission characteristics of rock masses. In this paper, the crack characteristics, mechanical characteristics, and acoustic emission characteristics of rock masses with different grain size compositions, different crack patterns, and different crack lengths were investigated under uniaxial compression. The rock masses were made of rock-like materials. The crack initiation locations and crack propagation directions were different for a specimen comprised of one grain size range compared with specimens comprised of two or three grain size ranges. The specimens comprised of one and three grain size ranges crack progressively. The specimen comprised of two-grain size ranges brittle fracture. The highest peak axial load was found in the specimens comprised of one grain size range. The results showed that tensile wing crack, anti-tensile wing crack, transverse shear crack, compression induced tensile crack, and surface spalling were produced in specimens with different crack orientations. The rock mass with 2 cm long crack started to produce cracks from the tip of the crack extending to the top and bottom surface, soon forming through cracks. The rock was brittle fracture. The axial load reached the maximum and then fell rapidly. The acoustic emission energy reached a rapid maximum and then decreased rapidly. The rock mass with 3 cm long fissures started to produce cracks that only extended from the tip of the fissures to the top surface but not to the bottom surface. The rock mass was progressively fractured. The axial load was progressively decreasing. The acoustic emission energy also rose and fell rapidly several times as the rock mass was progressively fractured. Different rock crack lengths led to different crack processes and crack patterns, resulting in very different acoustic emission characteristics.

Mental health issues caused by the COVID-19 pandemic greatly impact people’s daily lives. Individuals with an at-risk mental state are more vulnerable to mental health issues, and these may lead to onset of full psychotic illnesses. This study aimed to develop and evaluate an online health-promotion program for physical and mental health of the individuals with at-risk mental state during the COVID-19 pandemic. A single group study with pre- and post-tests was conducted in 39 young adults with at-risk mental state. The participants were provided with the online health-promotion program after completing the pretest. Via social media, the online counseling program released one topic of material (about 15–20 min) every two weeks and provided interactive counseling for specific personal health needs on the platform. Study questionnaires, physiological examination, and blood serum examination were completed at both pre- and post-tests. The participants showed significant improvements in mental risk, anxiety, and physical activity after participating in the program. Furthermore, those who did not complete the program had significantly more severe negative symptoms. These results imply that the online health-promotion program is effective and accessible under certain barriers such as the COVID-19 pandemic, but not for individuals with higher risk of more negative mental health symptoms.

Acupuncture is an alternative treatment for primary dysmenorrhea (PDM). However, mechanisms by which acupuncture exerts its analgesic properties are still unclear. This study aimed to explore the cerebral blood flow (CBF) response to verum and sham acupuncture treatments, and further investigate whether pre-treatment CBF is capable of assessing symptom changes after interventions. A total of 11 PDM patients in the verum group and 12 patients in the sham group participated in this study. Pain rating index (PRI), CBF, and gonadal hormone levels were acquired before and after 8-week treatments. Both verum and sham acupuncture treatments exert its analgesic effect on PDM after intervention as PRI reduced (p < 0.05). Blood gonadal levels were not significantly different after acupuncture in both groups (all p > 0.05). In the verum group, intervention-related decreases in CBF were observed in the right dorsal anterior cingulate cortex. In the sham group, regions identified as showing reductions in CBF after acupuncture included the left ventromedial prefrontal cortex, left caudate, and left insula. Patients with higher baseline CBF in the left precuneus and right hippocampus were accompanied with worse treatment response to acupuncture intervention. Mechanisms of verum and sham acupuncture treatments are dissimilar as manifested by different brain responses.

Primary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. Acupuncture has been suggested as an effective treatment of PDM that may modulate descending pain modulation systems. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation systems after acupuncture treatment in women with PDM. Thirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention to measure the spontaneous activity in brain. After the 8-week intervention, both verum and sham groups reported decreased menstrual pain. However, the cessation of decreased functional connectivity (FC) between periaqueductal gray matter and the regions associated with affective pain modulation and attention-related pain modulation were found in the verum but not in the sham group after the 8-week intervention. More decreased FC has been found in the region associated with non-specific effects of acupuncture intervention after the early stage of acupuncture intervention. These results indicated that verum acupuncture may intercept the altered FC in descending pain modulation systems in PDM.

Background. Anemia and pancytopenia are not uncommon in patients with chronic kidney disease (CKD). Nevertheless, there is insufficient literature analyzing bone marrow pathology in patients with CKD or end-stage kidney disease (ESKD) receiving dialysis. Methods. This observational cohort study included 22 patients with ESKD and 23 patients with CKD that received bone marrow biopsy and aspiration at Chang Gung Memorial Hospital. Demographic, hematological, and biochemical data were collected at the time of bone marrow study for analysis. Results. Bone marrow aspiration demonstrated that patients with ESKD had a lower percentage of blasts than patients with CKD (0.52 ± 0.84 versus 1.06 ± 0.78 %, p = 0.033). Bone marrow biopsy revealed that the overall incidence of hypocellular bone marrow was 55.6%. Furthermore, patients with ESKD had higher proportion of hypocellular bone marrow than patients with CKD (72.7% versus 39.1%, p = 0.023). In a multivariate logistic regression model, it was revealed that ESKD status (odds ratio 9.43, 95% confidence interval 1.66–53.63, p = 0.011) and megakaryocyte count within bone marrow (odds ratio 0.48, 95% confidence interval 0.29–0.79, p = 0.004) were significant predictors for bone marrow hypocellularity. Conclusion. Bone marrow hypocellularity is common in patients with kidney dysfunction. Hypocellular marrow occurs more frequently in patients with ESKD than patients with CKD.

We read with great interest the meta-analysis by Hall et al ,1 and congratulate the authors on their accomplishment of such a comprehensive literature review. However, we would like to raise a few concerns to caution readers on the study limitations regarding their data aggregation and analysis. First , the analysis included several studies that appeared duplicate considerably in their patient populations and thus similar data from the same patients were counted more than once (table 1).2 For example, four publications from the same study group at the Kaohsiung Chang Gung Memorial Hospital in Taiwan were included to calculate the cumulative incidence of clinical relapse after discontinuation of entecavir or tenofovir. The latest and also largest study by Ma et al 3 presumably contained data from most, if not all, patients enrolled in the three earlier studies. Second , some studies were composed of highly selected participants whose features differed significantly from those of a general population of patients with chronic hepatitis …

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.

The global aviation industry has been experiencing catastrophic disruption since the beginning of 2020 due to the unprecedented impact of the COVID-19 pandemic on air traffic. Although the decline in regular commercial air travel has caused tremendous economic loss to aviation stakeholders, it has also led to the reduction in the amount of recorded air pollutants. Most of the aircraft emissions are released during the cruise phase of flight, however they have relatively small impact on humans due to the fact that those emissions are released directly into the upper troposphere and lower stratosphere. Therefore, the scope of this study is to investigate the ground-level aircraft emissions from landing and take-off (LTO) cycles, as they have a greater influence on the ambient environment of the airports in a specific region. In this paper, we study the variation of typical air pollutant concentrations (i.e., HC, CO, and NOx) from the LTO cycles during the outbreak of COVID-19 pandemic in both temporal and spatial scales. These ground-level emissions are estimated for the 22 airports in the Yangtze River Delta, China. The results indicate that the variation pattern of the three air pollutants were significantly influenced by the dramatic onset of the COVID-19 pandemic, as well as the pertinent policies to suppress the spread of the virus. The results also reveal non-uniform distribution of the emission quantified at different airports. It is noticeable that the emission quantity generally declined from the east coast to the central and western part of the research region. Furthermore, discrepancies in the target markets also create disparities in the variation pattern of the emissions at different airports under the context of COVID-19.

Reports on the prevalence of torus mandibularis among dialysis patients have been limited and inconclusive. A wide variety of oral manifestations has been found in patients with hyperparathyroidism. Furthermore, uremia-related changes in facial bone structures have been described in the literature. This prospective observational study examined 322 hemodialysis patients treated at the Chang Gung Memorial Hospital from 1 August to 31 December 2016. Two subgroups were identified: patients with torus mandibularis (n = 25) and those without (n = 297). Clinical oral examinations including inspection and palpation were employed. Our study found that most mandibular tori were symmetric (84.0%), nodular (96.0%), less than 2 cm in size (96.0%), and located in the premolar area (92.0%). Poor oral hygiene was observed among these patients, with 49.7% and 24.5% scoring 3 and 4, respectively, on the Quigley-Hein plaque index. More than half (55.0%) of patients lost their first molars. Multivariate logistic regression analysis revealed that blood phosphate level (odds ratio = 1.494, p = 0.029) and younger age (odds ratio = 0.954, p = 0.009) correlated significantly with torus mandibularis. The prevalence of torus mandibularis in patients receiving hemodialysis in this study was 7.8%. Younger age and a higher blood phosphate level were predictors for torus mandibularis in these patients.

Simple Summary Systemic therapies for advanced biliarty tract cancers (BTC) are limited. The combination of gemcitabine with cisplatin (GC) has been the standard first-line treatment for advanced BTC from 2010 until now. In order to improve therapeutic effect, especially response rate, we added a novel schedule and dosage of bevacizumab to standard GC regimen. In our real world date, we found this regimen could increase the overall response rate to 50.0%, and side effects were managable. For patients with advanced BTC, especially whose tumors need rapid response to treatment, our regimen can provide an alternative choice. Abstract Background: Biliary tract cancer (BTC) is a heterogenous collection of biliary tract cancer at different primary sites, and the prognosis of advanced BTC is dismal. Systemic chemotherapy with gemcitabine and cisplatin (GC) has been the reference regimen since 2010. How to improve therapeutic effects of GC regimen is an urgent mission at present. Methods: Bevacizumab with a reduced dosage and modified schedule (10 mg/Kg/triweekly, 1 day before GS at the first 2 cycles) was combined with standard GC for patients with advanced BTC. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 every 2 months. Kaplan–Meier curves were estimated for time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS). Result: A total of thirty cases of advanced BTC accepted this treatment, and the overall response rate (ORR) was 50.0%, and the disease control rate was 80.0% for all patients. The median TTF was 5.8 months, the median PFS was 8.4 months, and the median OS was 13.6 months. Most responses were noted at the first evaluation. Adverse effects (AEs) were mostly tolerable. Conclusions: After modifying the schedule, adding bevacizumab to a traditional GC regimen could increase the ORR with a shorter time-to-response, a better PFS and OS than GC alone but without the addition of AE. This regimen can be applied to patients with advanced BTC, especially those who are with a big tumor burden and who need a rapid response.

The clinical presentation and survival of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication as compared to HCC in viremic patients are not well characterized. We aimed to investigate the characteristics and survival between HCV patients with and without viremia at HCC diagnosis.: We retrospectively analyzed overall survival outcomes in 1389 HCV-related HCC patients, including 301 with HCC developed after HCV eradication (post-SVR HCC) and 1088 with HCV viremia at HCC diagnosis (viremic HCC). We also evaluated overall survival in the two groups using propensity score-matching methods.: At HCC diagnosis, post-SVR HCC patients were older, less obese, less likely cirrhotic, with better liver function, lower alfa-fetoprotein levels, earlier BCLC stages, and higher rate of treatment with surgery. Overall, post-SVR HCC patients had higher median survival than viremic patients (153.3 vs. 55.6 months, p &lt, 0.01), but post-SVR HCC was not independently associated with survival on multivariate analysis (adjusted HR: 1.05, 95% CI: 0.76–1.47). However, on sub-analysis, viremic HCC patients who subsequently received anti-viral treatment and achieved SVR had higher median survival than post-SVR HCC patients (p &lt, 0.01). Viremic HCC with subsequent SVR was also significantly associated with lower mortality as compared to post-SVR HCC (adjusted HR: 0.18, 95% CI: 0.11–0.29). In addition, we observed similar findings in our analysis of the propensity score-matched cohorts.: The advantages in clinical and tumor characters at HCC diagnosis determined the better overall survival of post-SVR HCC patients, however, HCV eradication after HCC development was also associated with improved survival.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation). These cell lines were characterized in terms of pluripotency and differentiation potential. They serve as useful platforms to study alcohol metabolism and other chronic diseases associated with alcohol consumption.

Accurate risk prediction for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) may guide treatment strategies including initiation of antiviral therapy and also inform implementation of HCC surveillance. There have been 26 risk scores developed to predict HCC in CHB patients with (n = 14) or without (n = 12) receiving antiviral treatment; all of them invariably include age in the scoring formula. Virological biomarkers of replicative activities (i.e., hepatitis B virus DNA level or hepatitis B envelope antigen status) are frequently included in the scores derived from patients with untreated CHB, whereas measurements that gauge severity of liver fibrosis and/or reserve of hepatic function (i.e., cirrhosis diagnosis, liver stiffness measurement, platelet count, or albumin) are essential components in the scores developed from treated patients. External validation is a prerequisite for clinical application but not yet performed for all scores. For the future, higher predictive accuracy may be achieved with machine learning based on more comprehensive data.

Spectroscopic analysis has been widely used in medical research and healthcare testing including trace chemical, biochemical and immunoassay. We have developed a chip based spectrometer - SpectroChip based on novel MEMS technology. It has a spectral resolution of 5 nm with a spectral range of 350 1100 nm and a signal to noise ratio of 300:1. We have built a rapid test reader for COVID-19 antibody and antigen detection using our SpectroChip. Our SpectroChip technology will play a key role not only in disease control for COVID-19 pandemic but also in telemedicine and homecare health monitoring.

Blinatumomab, a bispecific T cell engager (BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive tumor cells and has been approved to treat relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce T cells’ number and cytotoxic function, leading to an inadequate response to blinatumomab treatment in patients. In addition, it was reported that a substantial portion of R/R B-ALL patients failing blinatumomab treatment had the extramedullary disease, indicating the poor ability of blinatumomab in treating extramedullary disease. In this study, we investigated whether the adoptive transfer of ex vivo expanded γ9δ2 T cells could act as the effector of blinatumomab to enhance blinatumomab’s antitumor activity against B-cell malignancies in vivo. Repeated infusion of blinatumomab and human γ9δ2 T cells led to more prolonged survival than that of blinatumomab or human γ9δ2 T cells alone in the mice xenografted with Raji cells. Furthermore, adoptive transfer of γ9δ2 T cells reduced tumor mass outside the bone marrow, indicating the potential of γ9δ2 T cells to eradicate the extramedullary disease. Our results suggest that the addition of γ9δ2 T cells to the blinatumomab treatment regimens could be an effective approach to enhancing blinatumomab’s therapeutic efficacy. The concept of this strategy may also be applied to other antigen-specific BiTE therapies for other malignancies.

Background: Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks.Methods: We analyzed stroke incidence rates in Taiwan’s Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke.Results: In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52–3.20; p < 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53–2.46; p < 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26–0.79; p < 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44–0.68; p < 0.001).Conclusion: These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.