Generation of induced pluripotent stem cells (ZZUCSBi001-A) from skin fibroblasts of a healthy donor.

Fibroblasts were extracted from the scalp of a healthy 55-year-old male and subsequently transformed into pluripotent stem cells by introducing episomal plasmids harboring essential reprogramming factors. These induced pluripotent stem cells exhibited a normal karyotype and demonstrated the capacity to differentiate into all three germ layers, as confirmed through teratoma assays. This specific cell line serves as a valuable reference for comparative investigations alongside other induced pluripotent stem cell lines generated from somatic cells of patients afflicted by genetic neurodegenerative disorders.

Esketamine-based opioid-free anaesthesia alleviates postoperative nausea and vomiting in patients who underwent laparoscopic surgery: study protocol for a randomized, double-blinded, multicentre trial.

BACKGROUND: Although opioids are commonly prescribed in clinical anaesthesia, the significant side effects attributed to their overuse are raising increasing concerns. One way to reduce perioperative opioid consumption is to apply opioid-reduced anaesthesia (ORA) and even opioid-free anaesthesia (OFA), which involves regional techniques, neuraxial anaesthesia, nonopioid analgesics or combined use. The aim of this study was to investigate whether the application of OFA by using esketamine in intraoperative analgesia could minimize the side effects of postoperative nausea and vomiting (PONV), as well as other short-term side effects related to anaesthesia. METHODS/DESIGN: The study was designed as a prospective, randomized, controlled, multicentre trial. A total of 278 patients were enrolled; participants were nonsmoking female patients aged 18-50 years and scheduled for laparoscopic appendectomy or cholecystectomy, ASA at I-III, with no serious physical or mental diseases. Both groups received usual perioperative care except for the analgesic medication of either esketamine or sufentanil. The primary outcome was the incidence of PONV 3 days after surgery. Secondary outcomes included recovery status, pain, sedation level and overall recovery, delirium and cognition, anxiety and depression and total consumption of analgesic agents. DISCUSSION: This trial may show that the synergy of esketamine and propofol anaesthesia reduces PONV as well as other short-term adverse events, thereby providing a better safety and satisfaction profile of ERAS for laparoscopic appendectomy and cholecystectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047169. Registered on June 9, 2021.

Progress in pH-Sensitive sensors: essential tools for organelle pH detection, spotlighting mitochondrion and diverse applications.

pH-sensitive fluorescent proteins have revolutionized the field of cellular imaging and physiology, offering insight into the dynamic pH changes that underlie fundamental cellular processes. This comprehensive review explores the diverse applications and recent advances in the use of pH-sensitive fluorescent proteins. These remarkable tools enable researchers to visualize and monitor pH variations within subcellular compartments, especially mitochondria, shedding light on organelle-specific pH regulation. They play pivotal roles in visualizing exocytosis and endocytosis events in synaptic transmission, monitoring cell death and apoptosis, and understanding drug effects and disease progression. Recent advancements have led to improved photostability, pH specificity, and subcellular targeting, enhancing their utility. Techniques for multiplexed imaging, three-dimensional visualization, and super-resolution microscopy are expanding the horizon of pH-sensitive protein applications. The future holds promise for their integration into optogenetics and drug discovery. With their ever-evolving capabilities, pH-sensitive fluorescent proteins remain indispensable tools for unravelling cellular dynamics and driving breakthroughs in biological research. This review serves as a comprehensive resource for researchers seeking to harness the potential of pH-sensitive fluorescent proteins.

Corrigendum: Comparative effectiveness of electroacupuncture VS neuromuscular electrical stimulation in the treatment of chronic low back pain in active-duty personals: A single-center, randomized control study.

[This corrects the article DOI: 10.3389/fneur.2022.945210.].

Alterations of actin cytoskeleton and arterial protein level in patients with obstructive jaundice.

Vascular hypo-responsiveness to vasopressors in patients with obstructive jaundice (OJ) is a common anesthetic event, which leads to perioperative complications and increased mortality. The cause of this clinical issue remains unclear. In this study, we estimated the actin cytoskeleton and arterial protein level in the artery of OJ patients by proteomic analysis. Ten patients with OJ due to bile duct diseases or pancreatic head carcinoma were enrolled, while another ten non-jaundice patients with chronic cholecystitis or liver hemangioma as the control group. Vascular reactivity to noradrenaline was measured before anesthesia on the day of surgery. Artery samples in adjacent tissues of removed tumor were collected and evaluated by 2-dimensional electrophoresis. Proteins with differential expression were detected by MALDI-TOF mass spectrometry with immunoblot confirmation. The results confirmed the phenomenon of vascular hypo-reactivity in OJ patients as suppressed aortic response to noradrenaline were existed in these patients. We also found that actin cytoskeleton and several actin-binding proteins were up- or down-regulated in the artery of OJ patients. These proteins changed in OJ patents might be the basic mechanism of vascular hypo-reactivity, further studies to uncover the role of these proteins in OJ is critical for clinical treatment of these patients.

A sensitive mitochondrial thermometry 2.0 and the availability of thermogenic capacity of brown adipocyte.

The temperature of a living cell is a crucial parameter for cellular events, such as cell division, gene expressions, enzyme activities and metabolism. We previously developed a quantifiable mitochondrial thermometry 1.0 based on rhodamine B methyl ester (RhB-ME) and rhodamine 800 (Rh800), and the theory for mitochondrial thermogenesis. Given that the synthesized RhB-ME is not readily available, thus, a convenient mitochondrial thermometry 2.0 based on tetra-methyl rhodamine methyl ester (TMRM) and Rh800 for the thermogenic study of brown adipocyte was further evolved. The fluorescence of TMRM is more sensitive (∼1.4 times) to temperature than that of RhB-ME, then the TMRM-based mito-thermometry 2.0 was validated and used for the qualitatively dynamic profiles for mitochondrial thermogenic responses and mitochondrial membrane potential in living cells simultaneously. Furthermore, our results demonstrated that the heterogenous thermogenesis evoked by ß3 adrenoceptor agonist only used overall up to ∼46% of the thermogenic capacity evoked by CCCP stimulation. On the other hand, the results demonstrated that the maximum thermogenesis evoked by NE and oligomycin A used up to ∼79% of the thermogenic capacity, which suggested the maximum thermogenic capacity under physiological conditions by inhibiting the proton-ATPase function of the mitochondrial complex V, such as under the cold activation of sympathetic nerve and the co-release of sympathetic transmitters.

Comparative effectiveness of electroacupuncture VS neuromuscular electrical stimulation in the treatment of chronic low back pain in active-duty personals: A single-center, randomized control study.

Introduction: Low back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP. Methods: The study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied via telephone visit. Results: Eighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%; P = 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%; P = 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs. Conclusion: Both the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments. Trial registration: ChiCTR, (ChiCTR2100043726); registered February 27, 2021.

Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma.

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

Obstructive Jaundice does not Change the Population Pharmacokinetics of Etomidate in Patients who Underwent Bile Duct Surgery.

BACKGROUND: Etomidate is commonly used in the induction of anesthesia. We have previously confirmed that etomidate requirements are significantly reduced in patients with obstructive jaundice and that etomidate anesthesia during Endoscopic Retrograde Cholangiopancreatography (ERCP) results in more stable hemodynamics compared to propofol. The aim of the present study is to investigate whether obstructive jaundice affects the pharmacokinetics of etomidate in patients who underwent bile duct surgery. METHODS: A total of 18 patients with obstructive jaundice and 12 non-jaundiced patients scheduled for bile duct surgery were enrolled in the study. Etomidate 0.333 mg/kg was administered by IV bolus for anesthetic induction. Arterial blood samples were drawn before, during, and up to 300 minutes after the bolus. Plasma etomidate concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A nonlinear mixed-effects population modeling approach was used to characterize etomidate pharmacokinetics. The covariates of age, gender, height, weight, Body Surface area (BSA), Body Mass Index (BMI), Lean Body Mass (LBM), Total Bilirubin (TBL), Alanine Aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), creatinine (CR), and blood urea nitrogen (BUN) were tested for significant effects on parameters using a multiple forward selection approach. Covariate effects were judged based on changes in the Objective Function Value (OFV). RESULTS: A three-compartment disposition model adequately described the pharmacokinetics of etomidate. The model was further improved when height was a covariate of total clearance [Cl1=1.30+0.0232(HT-162), ΔOFV=-7.33; P<0.01)]. The introduction of any other covariates, including bilirubin and total bile acids, did not improve the model significantly (P>0.01). For the height of 162cm, the final pharmacokinetic parameter values were as follows: V1=1.42 (95% CI, 1.01-1.83, L), V2=5.52 (95% CI, 4.07-6.97, L), V3=63.9 (95% CI, 41.95-85.85, L),Cl1= 1.30 (95% CI, 1.19-1.41, L/min), Cl2= 1.21 (95%CI, 0.95-1.47, L/min), and Cl3=0.584 (95%CI, 0.95-1.21, L/min), respectively. CONCLUSION: A 3-compartment open model might best describe the concentration profile of etomidate after bolus infusion for anesthesia induction. The pharmacokinetics of etomidate did not change by the presence of obstructive jaundice.

Association Between Procalcitonin and Post-hepatectomy Liver Failure in Hepatocellular Carcinoma Patients.

Objectives: Procalcitonin (PCT) has long been proved as an early diagnostic signal for postoperative outcomes. The purpose of this study is to explore the value of serum procalcitonin levels in predicting post-hepatectomy liver failure (PHLF), and further to declarethe relationship between postoperative PCT and short-term prognosis in patients after hepatectomy. Methods: Clinical data of patients with hepatocellular carcinoma (HCC) who underwent hepatectomy from June 1st, 2019 to September 31st, 2020 at Shanghai Eastern Hepatobiliary Surgery Hospital had been retrospectively analyzed. Logistic regression analysis was used to evaluate the risk factors related to PHLF. The Kaplan-Meier method was used to calculate the PHLF rate and 30-day survival after surgery. Results: A total of 885 patients with complete data were finally included in analysis, 311 of them with elevated serum PCT (≥1 ng/ml). Results of the logistic regression analysis suggested a significant association between PCT and PHLF [HR, 95%CI; 3.801 (1.825, 7.917), p < 0.001]. Other significant risk factors for PHLF included portal hypertension, portal blocking time (>30 min) and blood transfusion (>200 ml). Kaplan-Meier analysis also suggested a higher PHLF rate in elevated PCT patients [9.0% (95% CI, 7.3 to 12.8 VS. 1.9% (95% CI, 1.1-4.3)); p < 0.001]. For secondary outcomes, elevated PCT was also highly associated with postoperative sepsis, ICU admission, 30-day mortality and 3-month mortality. Conclusion: Elevated procalcitonin level in patients after hepatectomy is related to higher PHLF rate, with lower 30-day survival and poor short-term postoperative outcomes.

Efficacy of a Simplified Feedback Trainer for High-Quality Chest Compression Training: A Randomized Controlled Simulation Study.

Background: The most recent international guidelines recommended support training of chest compression (CC) using feedback devices. This study aimed to compare the training efficacy of a simplified feedback trainer with the traditional cardiopulmonary resuscitation (CPR) simulator in CPR training. Methods: A total of 60 soldiers were randomly allocated into three groups equally, trained with a simplified external cardiac massage (ECM) trainer named Soul SheathTM (SS) (SS group), a Resusci Anne manikin (RA group), or traditional simulation training with instructor feedback, respectively. After 7 days of training, the CPR skills were tested blindly in a 2-min assessment session. The primary outcome was the proportion of effective CC, and the secondary outcome included CC rate, depth, compression position, and extent of the release. Results: The percentage of effective CC achieved in the SS group was comparable with the RA group (77.0 ± 15.52 vs. 77.5 ± 10.73%, p = 0.922), and significantly higher than that in the control group (77.0 ± 15.52 vs. 66.8 ± 16.87%, p = 0.037). Both the SS and RA groups showed better CC performance than the control group in terms of CC rate (SS group vs. control group, P = 0.032 and RA group vs. control group, P = 0.026), the proportion of shallow CC (SS group vs. control group, P = 0.011 and RA group vs. control group, P = 0.017). No difference between the SS group and RA group was found in all the CC parameters. Conclusions: The simplified ECM trainer (SS) provides a similar efficacy to the traditional manikin simulator with feedback in CC training to improve the quality of CPR skills.

Folic acid alleviates jaundice of phenylhydrazine (PHA)-induced neonatal rats by reducing Lys-homocysteinylation of albumin.

Neonatal jaundice is a common symptom that occurs in neonates during the first month of their life and is generally divided into physiological and pathological subtypes. In serious cases, pathological neonatal jaundice frequently shows complications including seizures, cerebral palsy, and kernicterus. However, due to the unclear pathogenesis of pathological neonatal jaundice, effective drugs for this disease remain unsatisfied. In the present study, we first estimated the protective effects of folic acid (FA) on phenylhydrazine (PHA) or homocysteine (Hcy)-injected neonatal rats (2-3 days aged). Intriguingly, we found that FA significantly decreased the elevated total bilirubin (TBIL) and direct bilirubin (DBIL) concentration, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activity in PHA- or Hcy-injected rats, indicating that FA improves liver functions. Meanwhile, our results also showed that the plasma Hcy level and N-homocysteinylation (N-Hcy) modification of albumin were significantly elevated in the jaundice rats, which were obviously reversed after FA administration. Furthermore, we identified a novel N-Hcy modification site K545 of human serum albumin (HSA) using LC-MS/MS, and the mutagenesis assay in HEK293 further validated these observations. Besides, we demonstrated that the N-Hcy modification of albumin functionally inhibits the bilirubin-binding ability of albumin without altering its protein level both in vitro and in vivo. Altogether, we highlight a mechanism that FA reduces the plasma Hcy level and thereby enhance the bilirubin-binding ability of albumin, which may provide a novel therapeutic strategy for the treatment of pathological neonatal jaundice.

Baseline neutrophil-lymphocyte ratio is associated with survival for infant living donor liver transplantation for biliary atresia.

Living donor liver transplantation (LDLT) in infants for congenital biliary atresia (BA) poses various challenges nowadays. We aim to investigate independent preoperative risk factors for LDLT in infants. We retrospectively analyzed medical records of infant patients who underwent LDLT surgery for BA from 1 July 2014 to 31 December 2016. Cox regression was used to explore risk factors. The Kaplan-Meier method was used to calculate the recipient and graft survival, and subgroup analysis was then applied according to the risk factors. Independent t test or Mann-Whitney U test was applied for comparison of certain factors between survival patients and death. A total of 345 infant LDLT for BA were included in the analysis. In the multivariate Cox-regression model, 3 factors were determined as independent risk factors for recipient and graft survival, there were neutrophil-lymphocyte ratio (NLR), pediatric end-stage liver disease (PELD), and recipient age. The HR (95% CI) of baseline NLR for recipient and graft survival were 1.25 (1.12-1.38) and 1.25 (1.13-1.39), with all P < .0001. Kaplan-Meier curves for NLR using different cut-offs (1.5; 1, 2) suggested that higher baseline NLR was significantly associated with recipient and graft survival. The subgroup analysis indicated that for infants with elevated NLR, the recipient survival was significantly lower when their age >6 months or PELD >20. Our results indicate that infants with higher baseline NLR value may have lower survival rate 3 years after transplantation. Further investigations about broaden the application of pre- and post-transplant NLR to guide nutrition intervention and immunosuppression therapy are necessary.

[Sources and Control Area Division of Ozone Pollution in Cities at Prefecture Level and Above in China].

Based on the ground-level ozone concentration monitoring data in 2018, the ozone concentrations in 338 cities at the prefecture level and above were analyzed, and the TCEQ method was utilized to calculate the amount of locally generated ozone and regionally transported ozone in each city to divide the national ozone pollution control area and develop appropriate ozone pollution control measures. Correlation analysis was conducted between the amount of locally generated ozone and the daily maximum 8 h average ozone in each city to determine the main source of ozone pollution by determination coefficient (R2). The results show that 121 cities (35.8%) in China exceeded the standard in O3 concentration in 2018. The local generation of O3 in 104 cities has a great impact on the local O3 pollution, and is its main cause. In the other 234 cities, the main source of O3 pollution is regionally transported O3. Cities are classified into four categories based on their ozone concentration levels and pollution sources:cities with a nonattainment ozone situation and mainly locally generated ozone (N-L), cities with a nonattainment ozone situation and mainly regionally transported ozone (N-T), cities with a standard ozone situation and mainly locally generated ozone (S-L), and cities with a standard ozone situation and mainly regionally transported ozone (S-T). Finally, according to the proportion of four city types in each province, the whole country is divided into three types of control areas:severe, moderate, and general. N-L cities in the severe control area account for the largest proportion (20.3%) of the three types of control areas and the pollution is the highest; the proportion of the four categories of cities in the moderate control area are all medium; the general control area mainly includes S-T cities (65.4%), and the pollution is the lowest.

Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study.

BACKGROUND: Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. METHODS: A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. RESULTS: A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. CONCLUSION: This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

Living Donor Liver Transplantation in Children: Perioperative Risk Factors and a Nomogram for Prediction of Survival.

BACKGROUND: Living donor liver transplantation (LDLT) in children has achieved promising outcomes during the past few decades. However, it still poses various challenges. This study aimed to analyze perioperative risk factors for postoperative death in pediatric LDLT. METHODS: We retrospectively analyzed medical records of pediatric patients who underwent LDLT surgery from January 1, 2014, to December 31, 2016, in our hospital. Predictors of mortality following LDLT were analyzed in 430 children. Cox regression and Kaplan-Meier curve analysis were used for covariates selection. A nomogram was developed to estimate overall survival probability. The performance of the nomogram was assessed using calibration curve, decision curve analysis, and time-dependent receiver operating characteristic curve. RESULTS: Among the 430 patients in this cohort (median [interquartile range] age, 7 [6.10] mo; 189 [43.9%] female; 391 [90.9%] biliary atresia), the overall survival was 91.4% (95% confidence interval, 89.2-94.4), and most of the death events (36/37) happened within 6 months after the surgery. Multivariate analysis indicated that the Pediatric End-stage Liver Disease score, neutrophil lymphocyte ratio, graft-to-recipient weight ratio, and intraoperative norepinephrine infusion were independent prognostic factors. A novel nomogram was developed based on these prognostic factors. The C index for the final model was 0.764 (95% confidence interval, 0.701-0.819). Decision curve analysis and time-dependent receiver operating characteristic curve suggested that this novel nomogram performed well at predicting mortality of pediatric LDLT. CONCLUSIONS: We identified several perioperative risk factors for mortality of pediatric LDLT. And the newly developed nomogram can be a convenient individualized tool in estimating the prognosis of pediatric LDLT.

[Driving Factors of the Significant Increase in Surface Ozone in the Beijing-Tianjin-Hebei Region, China, During 2013-2018].

Photochemical pollution, which is believed to be influenced by emission changes and meteorological factors, is presently quite serious in the Beijing-Tianjin-Hebei (BTH) region, China. There is a need to ascertain the effectiveness of air quality management in the region based on long-term air quality trends independent from meteorological influences. We apply Kolmogorov-Zurbenko (KZ) filtering, a technique used to separate different scales of motion in a time series, to analyze the time series of the maximum daily 8-hour running average for ozone (O3-8h) from 13 cities in the BTH region during 2013-2018, and also discuss trends and driving factors. Results of the KZ filtering revealed that the short-term, seasonal, and long-term components of the O3-8h accounted for 32.7%, 63.9%, and 3.4% of the total variance, respectively. The long-term component of the BTH region was much higher than of those reported by others for Berlin, Paris, and London, and was comparable to that of Los Angeles in the early 1990s and in the 4 years previous to our study. Although we found a lower long-term component than of those reported for Shanghai and Nanjing in the Yangtze River Delta, China, the BTH region had higher rates of increase that ranged from 2.31 to 7.12 µg·(m3·a)-1[mean 4.97 µg·(m3·a)-1]. Based on the linear fitting results-that had not been verified by experiments or model simulations-the average increase rates could be mainly attributed to emission changes (90.4%), which may be distinguished into two parts, the decrease of particulate matter (PM) (27.3%) and the emission of O3 precursors (63.1%). Decreases of PM2.5in Beijing, Langfang, Tianjin, and Hengshui were considered to be responsible for the increase at the levels of 50.8%, 32.5%, 36.7%, and 48.6%, respectively. This suggests that the rapid decrease in PM2.5 could be the most important factor in the increasing trend of O3 in some cities. We conclude that further decreases in the emission of O3 precursors are required to overcome the effect of decreasing PM2.5 causing an increase in O3.

Living Donor Liver Transplantation in Biliary Atresia Children with Pulmonary Hypertension.

OBJECTIVE: Though living donor liver transplantation (LDLT) is commonly performed for pediatric patients with biliary atresia (BA), pulmonary hypertension (PH) is seldom encountered or reported previously. The aim of this study is mainly to identify the prevalence of PH in pediatric patients undergoing liver transplantation and assess whether PH significantly augment the operative risk and evaluate the outcomes in this series of patients. DESIGN: Retrospectively cohort study. SETTING: Renji hospital, Shanghai, China. PARTICIPANTS: This study comprised 161 pediatric patients undergoing LDLT. INTERVENTIONS: Patient diagnosed of PH in preoperative examination was compared to those without PH in intra- or post- operative complications or outcomes. MEASUREMENTS AND MAIN RESULTS: We collected clinical records of LDLT surgery for pediatric patients during the year of 2016 in our hospital. Results suggested that pediatric patients undergoing LDLT had a substantial number of PH with a prevalence of 16.1% in this study. No significant difference was identified between two groups of patients regarding intraoperative outcomes and postoperative complications and mortality. CONCLUSION: LDLT is a safe procedure in a selected group of BA patients with PH, however, further long-term clinical investigations and mechanical researches are needed.

History and progress of hypotheses and clinical trials for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.