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Shameema Sikder,1 Jia Luo,2 P Pat Banerjee,2 Cristian Luciano,2 Patrick Kania,2 Jonathan C Song,1 Eman S Kahtani,3 Deepak P Edward,1,3 Abdul-Elah Al Towerki3 1Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA; 2College of Engineering, University of Illinois at Chicago, Chicago, IL, USA; 3King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia Purpose: To evaluate a haptic-based simulator, MicroVisTouch™, as an assessment tool for capsulorhexis performance in cataract surgery. The study is a prospective, unmasked, nonrandomized dual academic institution study conducted at the Wilmer Eye Institute at Johns Hopkins Medical Center (Baltimore, MD, USA) and King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia).Methods: This prospective study evaluated capsulorhexis simulator performance in 78 ophthalmology residents in the US and Saudi Arabia in the first round of testing and 40 residents in a second round for follow-up.Results: Four variables (circularity, accuracy, fluency, and overall) were tested by the simulator and graded on a 0–100 scale. Circularity (42%), accuracy (55%), and fluency (3%) were compiled to give an overall score. Capsulorhexis performance was retested in the original cohort 6 months after baseline assessment. Average scores in all measured metrics demonstrated statistically significant improvement (except for circularity, which trended toward improvement) after baseline assessment. A reduction in standard deviation and improvement in process capability indices over the 6-month period was also observed.Conclusion: An interval objective improvement in capsulorhexis skill on a haptic-enabled cataract surgery simulator was associated with intervening operating room experience. Further work investigating the role of formalized simulator training programs requiring independent simulator use must be studied to determine its usefulness as an evaluation tool. Keywords: medical education, computer simulation, educational assessment, technology assessment, cataract surgery

Naproxcinod, a cyclooxygenase-inhibiting nitric oxide donor, is pending FDA approval for the indications of knee and hip osteoarthritis. Treating osteoarthritis pain can be challenging because many agents commonly used for this indication carry potential risk for increased cardiovascular events including increased blood pressure, increased upper gastrointestinal (GI) bleeding, and increased hepatotoxicity. Naproxcinod combines the action of the parent drug, naproxen, with nitric oxide, with the intent of minimizing potential hypertensive and GI adverse effects while maintaining the analgesic effects. Available clinical trial data indicates that naproxcinod has superior efficacy for pain compared with placebo, does not increase blood pressure, but has not been shown to lower the incidence of gastroduodenal ulcer compared with naproxen therapy. The most commonly reported adverse effects include headache, back pain, arthralgia, nausea, dyspepsia, and upper abdominal pain. Unresolved issues include gastroprotective effects of naproxcinod, recommended dosing in patients with chronic kidney disease, and the drug interaction profile of this agent. [ABSTRACT FROM AUTHOR]

Rivaroxaban is a highly potent direct factor Xa inhibitor with competitive and reversible activity that is pending FDA approval for the indication of venous thromboembolism (VTE) prophyiaxis in patients undergoing total knee replacement (TKR) or totai hip replacement (THR) surgery. Unlike the currently prescribed VTE prophylactic agents, which require subcutaneous (SC) administration or exhibit an undesirable drug interaction/monitoring profile, this agent offers the convenience of once-daily oral dosing, without the inconvenience of laboratory monitoring. In multiple phase 3 trials, rivaroxaban has demonstrated superior efficacy compared with enoxaparin in preventing VTE in patients undergoing THR and TKR, with comparable rates of major bleeding. The most commonly reported adverse events associated with rivaroxaban treatment include anemia, nausea, elevations in iivertransaminases (short-term, with comparable incidence to that of enoxaparin), and postprocedural hemorrhage. Unresolved issues include the long-term hepatotoxicity profile of rivaroxaban and a potential risk of precipitating adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a disorder that affects >2 million people in the United States. First-line antiarrhythmic agents (per American College of Cardiology/American Heart Association/ European Society of Cardiology guidelines) that are currently used to treat recent-onset AF work by indiscriminately blocking various ionic channels, thereby inducing a prolonged ventricular action potential duration or possibly inducing ventricular arrhythmias in the presence of myocardial ischemia because of excessive conduction slowing in diseased cardiac tissue. Vernakalant is an atrial-selective, potassium- and sodium-channel-blocking agent awaiting FDA approval for the indication of conversion of recent-onset AF to normal sinus rhythm. This agent offers a novel mechanism of action for the acute conversion of AF, as it specifically targets the potassium channel underlying the ultrarapid delayed rectifier current that is found only in atrial myocytes, along with other potassium channels. Pivotal phase 3 clinical trials have demonstrated that patients with recent-onset AF (

Ramelteon (Takeda Pharmaceuticals) is a selective melatonin receptor agonist awaiting FDA approval for the treatment of insomnia. Unlike the currently prescribed hypnotic agents that work by targeting gamma-aminobutyric acid (GABA) receptors, ramelteon offers a novel mechanism of action, specifically targeting the MT[1] and MT[2] receptors in the brain, which are thought to play a role in regulating sedation and circadian rhythms. Ramelteon is characterized by undergoing extensive first-pass metabolism along with having high oral bioavailability. Results of phase 2 clinical trials have demonstrated that ramelteon-treated patients had significantly shorter sleep onset latencies and longer total sleep times than placebo treated patients. Furthermore, ramelteon therapy did not appear to impair patient cognition, memory recall, levels of alertness, or ability to concentrate. Data from animal studies suggest that ramelteon is not likely to cause abuse or physical dependence. Unlike the current FDA-approved hypnosedatives, ramelteon has been evaluated in trials for periods of up to 1 year. Results from multiple phase 1/2 studies indicate that the most commonly reported adverse effects include somnolence, headache, fatigue, nausea, and dizziness. [ABSTRACT FROM AUTHOR]

Efalizumab (Raptiva, Genentech/Xoma) is a humanized monoclonal antibody of CD11a that exerts its effect through the blockade of the interaction between leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) FDA recently granted approval for efalizumab in the treatment of chronic moderate-to-severe plaque psoriasis in adults aged 18 years and older. Efalizumab does not achieve clinical response rates equal to cyclosporine or methotrexate, but it lacks the systemic organ toxicities of these agents and is associated with a more rapid onset of action (significant improvements in Psoriasis Area and Severity Index [PAST] response after 2 doses). In addition, efalizumab will likely compete with another approved biologic, alefacept, and off-label use of 2 other biologics currently on the market, etanercept and Infliximab. Phase 3 studies have shown efalizumab to be safe and effective at once weekly doses of 1 mg/kg to 2 mg/kg SC for this indication. Similar to alefacept, efalizumab IS administered on a once-weekly basis, but alefacept is administered as an IV bolus or given as an IM dose, whereas efalizumab is administered as a SC dose. Efalizumab's duration of remission of 60 to 84 days suggests that it is a suppressive agent. This is in contrast to psoralen with ultraviolet A (PUVA) and alefacept, 2 remittive agents that produce prolonged remissions of 6 to 12 months and 7 months, respectively. Known adverse effects are mild and decrease in frequency after 3 doses, although the FDA's Dermatologic & Ophthalmic Drugs Advisory Committee initially expressed concerns about the increased incidence of serious infection, such as pneumonia, sepsis, cellulitis, and gastroenteritis (0.4% for efalizumab-treated patients compared with 0.1% for placebo recipients). At this time, until further studies comparing efalizumab to other drugs indicated, for the treatment of psoriasis are completed and post marketing surveillance is conducted, the agent's place on the formulary remains unclear. [ABSTRACT FROM AUTHOR]

Eplerenone is a selective aldosterone receptor antagonist under FDA review for the treatment of hypertension. Eplerenone is a 9\'02, 11\'02-epoxyDSsubstituted derivative of spironolactoneDLthe only aldosterone antagonist currently approved in the United States. Eplerenone has a trough-to-peak ratio greater than 90%, making it suitable for once-daily dosing. Placebo-controlled trials have shown that eplerenone 25 to 200 mg/d, alone or in combination with other antihypertensives, significantly reduces blood pressure (BP) in patients with mild to severe hypertension. In addition, comparative trials have shown eplerenone to have a potent antihypertensive effect similar to that of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers, and spironolactone. Because eplerenone has a lower binding affinity for androgenic and progestogenic receptors than spironolactone does, investigators hope eplerenone will have a lower incidence of endocrine-related adverse effects (gynecomastia, breast tenderness, and menstrual irregularities). Preliminary data seem to support this, but further study is needed. Hyperkalemia (K+ > 6 mEq/l) has been reported in clinical trials, most commonly when eplerenone was given concurrently with an ACE inhibitor. Eplerenone neither induces nor inhibits the CYP P450 isoenzyme system; however, it is extensively metabolized by the 3A4 isoenzyme. Eplerenone's potential for drug interactions has not been extensively investigated, and further studies need to be conducted. The effects of eplerenone on mortality, hospitalization, quality of life, and cost of care in patients with congestive heart failure are currently under investigation in phase III trials. An additional new drug application (NDA) for this potential indication is expected to be filed in early 2003. [ABSTRACT FROM AUTHOR]

Alefacept (Amevive is the first immunosuppressive agent directed specifically to inhibit the activation of, and possibly kill, T cells, which are thought to be responsible for the release of cytokines that stimulate the hyperproliferation of kerationcytes, leading to psoratic plaques and inflammation. FDA's Dermatologic and Ophthalmic Drug Advisory Committee recently recommended alefacept for approval as a first-line therapy against moderate to severe plaque psoriasis. If approved, it will join psoralen ultraviolet A (PUVA), acitretin, methotrexate, and cyclosporine as treatments for severe psoriasis but will offer the advantage of avoiding the severe adverse effects associated with their long-term use. Alefacept may compete with off-label use of the biologies currently on the market, enbrel (Etanercept) and infliximab (Remicade), Placebo-controlled trials have shown alefacept to be safe and effective at once-weekly doses of 7.5 mg IV and 15 mg IM for this indication. The duration of response following one 12-week course of IV alefacept was shown to be longer than 7 months in Phase II and Phase III clinical trials. Known adverse effects are mild, although the FDA advisory committee remains concerned about the potential for infections and malignancies because of reduced lymphocyte counts. Although alefacept has shown activity against psoriatic arthritis, furthe study is needed. [ABSTRACT FROM AUTHOR]

Tadalafil (IC351) is a selective inhibitor of phosphodiesterase 5 (PDE5) under FDA review for treatment of erectile dysfunction (ED) and diabetes-related ED. If approved, it will join the widely used PDE5 inhibitor sildenafil citrate as an oral therapy for ED management. Placebo-controlled trials have shown tadalafil to be safe and effective at doses of 5 to 25 mg for treating ED and doses of 10 to 20 mg for treating diabetes-related ED. Tadalafil is rapidly absorbed, and patients have shown responsiveness (with multiple successful intercourse attempts) for up to 24 hours after administration. Tadalafil undergoes hepatic metabolism and is largely metabolized by the cytochrome P-450 3A4 isoenzyme. Headache and dyspepsia have been the most common adverse effects reported with the drug. According to the results from the largest clinical trials conducted to date, tadalafil has produced no abnormal visual effects and no clinically significant changes in blond pressure or electrocardiographic parameters. [ABSTRACT FROM AUTHOR]

Omapatrilat is a novel agent that inhibits both neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling. ACE inhibition counteracts the compensatory activation of the renin angiotensin system following chronic NEP inhibition. Omapatrilat can be dosed once a day and does not require dose adjustment for renal dysfunction or mild hepatic dysfunction. Clinical hypertension trials have established its efficacy at doses from 10 to 80 mg once daily in patients with mild to moderate hypertension. Heart failure trials to date have shown comparable efficacy between omapatrilat 40 mg and lisinopril 20 mg once daily in improving exercise tolerance in patients with NYHA class II/III heart failure. There is a strong suggestion that omapatrilat may also improve clinical outcomes in heart failure to a greater extent than lisinopril. The most common adverse effects reported with ornapatrilat include dizziness, hypotension, edema, fatigue, and diarrhea. [ABSTRACT FROM AUTHOR]

Olmesartan medoxomil (CS-866) is an angiotensin II receptor blocker under FDA review for treatment of hypertension. It is a tetrazolylbiphenyl-substituted imidazole derivative that undergoes de-esterification to form its active metabolite, olmesartan. The steady-state AUC and peak plasma concentration of olmesartan increase linearly with dose. The drug's absolute bioavailability is 26%, which falls in the middle of the range seen with the six FDA-approved ARBs (losartan, valsartan, irbesartan, candesartan, eprosartan, and telmisartan). Like the six other ARBs, olmesartan medoxomil can be taken once daily without regard to meals. Placebo-controlled trials have established its safety and efficacy at doses from 2.5 to 80 mg once daily in patients with mild to moderate hypertension. In addition, a comparative trial has shown olmesartan medoxomil to have a more potent antihypertensive effect than losartan and valsartan. Its dose-response curve plateaus at 20 to 40 mg. Because this agent does not undergo P-450-mediated biotransformation, its likelihood o drug interactions is minimal. [ABSTRACT FROM AUTHOR]

Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport., (© 2024. The Author(s).)

This study conducted in the Kyungpook National University Eco-friendly Agriculture Research Centre between 2022 and 2023 investigates the environmental implications of fence-type solar photovoltaic (PV) systems in diverse agricultural settings. Despite the increasing adoption of solar energy for climate change mitigation, there is a noticeable gap in research regarding the potential environmental impact of these specific PV systems. Focusing on heavy metal concentrations, including Cadmium (Cd), Copper (Cu), Arsenic (As), Mercury (Hg), Lead (Pb), Hexavalent Chromium (Cr +6 ), Zinc (Zn), and Nickel (Ni), across distinct fields, the study reveals significant fluctuations. Notably, the Rice Field experienced a substantial increase in Cd levels from 0.47 mg/kg in 2022 to 1.55 mg/kg in 2023, while Cu and Pb concentrations decreased to acceptable levels in 2023. The findings underscore the dynamic nature of heavy metal concentrations, emphasizing the importance of continuous soil quality monitoring to prevent contamination. This research provides valuable insights into the impact of fence-type solar PV system installations on agricultural soil quality, emphasizing the urgent need to secure these ecosystems through vigilant monitoring and environmental management practices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Recovery time is a crucial factor in ensuring the safety and effectiveness of both patients and endoscopy centers. Propofol is often preferred due to its fast onset and minimal side effects. Remimazolam is a new intravenous sedative agent, characterized by its rapid onset of action, quick recovery and organ-independent metabolism. Importantly, its effect can be specifically antagonized by flumazenil. The primary goal of this study is to compare the recovery time of remimazolam besylate and propofol anesthesia during endoscopic procedures in elderly patients. Methods: 60 patients aged 65-95 years who underwent gastrointestinal endoscopy were randomly and equally assigned to two groups: the remimazolam group (Group R) and the propofol group (Group P). The primary measure was the recovery time, defined as the time from discontinuing remimazolam or propofol until reaching an Observer's Assessment of Alertness and Sedation scale (OAA/S) score of 5 (responds readily to name spoken in normal tone). The time required to achieve an OAA/S score of 3 (responds after name spoken loudly or repeatedly along with glazed marked ptosis) was also recorded and compared. Results: The recovery time for Group R (2.6 ± 1.6 min) was significantly shorter than that for Group P (10.8 ± 3.0 min), with a 95% confidence interval (CI): 6.949-9.431 min, p <0.001. Similarly, the time to attain an OAA/S score of 3 was significantly less in Group R (1.6 ± 0.9 min) compared to Group P (9.6 ± 2.6 min), with a 95% CI: 6.930-8.957 min, p <0.001. Conclusion: Our study demonstrated that remimazolam anesthesia combined with flumazenil antagonism causes a shorter recovery time for elderly patients undergoing gastrointestinal endoscopy compared to propofol. Remimazolam followed by flumazenil antagonism provides a promising alternative to propofol for geriatric patients, particularly during gastrointestinal endoscopy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction., Methods: Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min., Results: The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC., Conclusion: This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Wang, Fu, Chen, Tang, Deng, Yang and Liu.)

Background: /Purpose: The Pediatric Eating Assessment Tool-10 (Pedi-EAT-10) is a caregiver-administrated subjective questionnaire for evaluating swallowing and feeding disorders among children. This study translated the Pedi-EAT-10 into Traditional Chinese and tested the translated version's reliability and validity., Methods: Pedi-EAT-10 was translated into Traditional Chinese by experts and finalized after discussion and testing. A total of 168 participants, consisting of 32 children with dysphagia from a tertiary medical center and 136 healthy controls from its Children Care Center for Employees, were recruited. All participants were assessed by an otolaryngologist and speech-language pathologist. The reliability, validity, and efficacy of the translated Pedi-EAT-10 were analyzed to ensure it could be used to identify pediatric dysphagia and feeding problems., Results: The Traditional Chinese version of the Pedi-EAT-10 had significant clinical discriminative validity between the dysphagia group and the control group (total score = 9.6 vs. 2.6, P < 0.001), acceptable test-retest reliability (intraclass correlation = 0.63), and excellent internal consistency (Cronbach's α = 0.91 for the entire cohort). The overall performance of the test for distinguishing children with dysphagia from normal controls was acceptable, and the area under the curve was 74.8% (sensitivity = 71.9%; specificity = 69.9%). The optimal cutoff score was ≥3 on the Youdex index., Conclusions: The Traditional Chinese version of the Pedi-EAT-10 has fair reliability and validity and can be quickly and easily completed by caregivers. The translated Ped-EAT-10 can be used as a first-line tool for assessing the need for further referral and instrumental examination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC., Methods: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0., Results: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05)., Conclusions: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment., (Copyright © 2023 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Objectives: Our previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation., Methods: A bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique., Results: The time to LORR induced by etomidate was significantly decreased in the BDL groups (p < 0.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (p < 0.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (p < 0.05). A bilirubin concentration of 1.0 μM increased the GABA-induced currents of rat cortical pyramidal neurons (p < 0.05). Furthermore, 1.0 μM bilirubin enhanced GABA-induced currents modulated by etomidate (p < 0.05)., Conclusions: Our results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy., Methods: Ninety adult patients were randomly assigned to Group Control, Group DEX0.5 (0.5 μg/kg dexmedetomidine) or Group DEX1.0 (1.0 μg/kg dexmedetomidine). Anaesthesia during endoscopy was implemented by plasma target-controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 μg/mL and the consecutive adjacent concentration gradient was 0.5 μg/mL. Median effective concentration (EC 50 ) of propofol by TCI for gastrointestinal endoscopy was determined by using the modified Dixon's up-and-down method. Cardiovascular variables were also measured., Results: EC 50 of propofol by TCI and 95% confidence interval (CI) for gastrointestinal endoscopy were 3.77 (3.48-4.09), 2.51 (2.27-2.78) and 2.10 (1.90-2.33) μg/mL in Group Control, Group DEX0.5 and Group DEX1.0, respectively. The average percent change from heart rate (HR) baseline was 2.8 (8.9), -7.4 (7.7) and -10.5 (8.8) (P < .001), and the average percent change from mean arterial pressure (MAP) baseline was -10.6 [-24.7; 3.5], -9.5 [-29.2; 11.4] and -4.0 [-27.3; 15.5] (P = .034) in Group Control, Group DEX0.5 and Group DEX1.0, respectively., Conclusions: Dexmedetomidine reduced the EC 50 of propofol by TCI. A 0.5-1 μg/kg dose of dexmedetomidine caused a decrease in HR without bradycardia. The decrease in dosage of propofol with increasing doses of dexmedetomidine caused more stable MAP. Dexmedetomidine is an ideal adjuvant drug to propofol during gastrointestinal endoscopy., (© 2022 British Pharmacological Society.)

Nuclear pore complex in the nuclear envelope plays an important role in controlling the transportation of RNAs, proteins and other macromolecules between the nucleus and cytoplasm. The relationship between abnormal expression of nucleoporins and cardiovascular diseases is unclear. In this study we investigated how myocardial infarction affected the expression and function of nucleoporins in cardiomyocytes. We separately knocked down 27 nucleoporins in rat primary myocardial cells. Among 27 nucleoporins, knockdown of Nup93, Nup210 and Nup214 markedly increased the expression of ANP and BNP, two molecular markers of cardiomyocyte function. We showed that Nup93 was significantly downregulated in hypoxic cardiomyocytes. Knockdown of Nup93 aggravated hypoxia-induced injury and cell death of cardiomyocytes, whereas overexpression of Nup93 led to the opposite effects. RNA-seq and bioinformatics analysis revealed that knockdown of Nup93 did not affect the overall transportation of mRNAs from the nucleus to the cytoplasm, but regulated the transcription of a large number of mRNAs in cardiomyocytes, which are mainly involved in oxidative phosphorylation and ribosome subunits. Most of the down-regulated genes by Nup93 knockdown overlapped with the genes whose promoters could be directly bound by Nup93. Among these genes, we demonstrated that Nup93 knockdown significantly down-regulated the expression of YAP1. Overexpression of YAP1 partially rescued the function of Nup93 knockdown and attenuated the effects of hypoxia on cell injury and cardiomyocyte death. We conclude that down-regulation of Nup93, at least partially, contributes to hypoxia-induced injury and cardiomyocyte death through abnormal interaction with the genome to dynamically regulate the transcription of YAP1 and other genes. These results reveal a new mechanism of Nup93 and might provide new therapeutic targets for the treatment of ischemia-induced heart failure., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

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., (© 2023. The Author(s).)

Purpose: When dexmedetomidine is used in elderly patients, high incidence of bradycardia is reported. Given age-related physiological changes in this population, it is necessary to know the safety margin between the loading dose of dexmedetomidine and bradycardia. Therefore, we conducted this study to investigate the median effective dose (ED50) of dexmedetomidine causing bradycardia in elderly patients. Methods: Thirty patients with ages over 65 years undergoing elective general surgery were enrolled. The Dixon and Massay sequential method were applied to determine the loading dose of dexmedetomidine, starting from 1.0 µg/kg. The dose for the follow-up subjects increased or decreased according to the geometric sequence with the common ratio 1.2, based on the 'negative' or 'positive' response of the previous subject. Positive mean that the subject developed bradycardia during the test. Hemodynamic data including heart rate and systolic blood pressure were recorded. The level of sedation was assessed with the Observer Assessment of Alertness and Sedation Scale (OAA/S). Results: Bradycardia occurred in 13 patients (43.3%). The ED50 of dexmedetomidine causing bradycardia was 1.97 µg/kg (95% CI, 1.53-2.53 µg/kg). OAA/S scores at 10 min after the beginning of the dexmedetomidine infusion and 10 min after the termination of dexmedetomidine administration showed no significant differences between the positive and negative groups ( P > 0.05). Conclusion: The ED50 of dexmedetomidine causing bradycardia in our cohort was higher than clinical recommended dose. A higher loading dose appears acceptable for a faster onset of sedation under careful hemodynamic monitoring. Trial registration: ChiCTR 15006368., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: To explore if chest high-resolution computed tomography (HRCT) can make higher accurate stages for thoracic sarcoidosis stage than X-ray (CRX) only., Methods: Clinical data from medical records of consecutive patients with a confirmed diagnosis of pulmonary sarcoidosis at Shanghai Pulmonary Hospital from January 1 2012 to December 31 2016 and consecutive patients treated at the Sarcoidosis Center of University of Cincinnati Medical Center, Ohio, USA from January 1 2010 to December 31 2015 were reviewed. The clinical records of 227 patients diagnosed with sarcoidosis (140 Chinese and 87 American) were reviewed. Their sarcoidosis stage was determined by three thoracic radiologists based on CXR and HRCT presentations, respectively. The stage determined from CXR was compared with that determined from HRCT., Results: Overall, 50.2% patients showed discordant sarcoidosis stage between CXR and HRCT (52.9% in Chinese and 44.8% in American, respectively). The primary reason for inconsistent stage between CXR and HRCT was failure to detect mediastinal lymph node enlargement in the shadow of the heart in CXR (22.1%) and small nodules because of the limited resolution of CXR (56.6%). Stage determined from HRCT negatively correlated with carbon monoxide diffusing capacity (DLCO) significantly (P < .01) but stage determined from CXR did not. Pleural involvement was detected by HRCT in 58 (25.6%) patients but only in 17 patients (7.5%) by CXR. Patients with pleural involvement had significantly lower forced vital capacity and DLCO than patients without it (both P < .05)., Conclusion: Revised staging criteria based on HRCT presentations included 5 stages with subtypes in the presence of pleural involvement were proposed. Thoracic sarcoidosis can be staged more accurately based on chest HRCT presentations than based on CXR presentations. Pleural involvement can be detected more accurately by HRCT., (© 2022. The Author(s).)

It is generally accepted that geriatric patients are more sensitive to propofol than adults; thus, a dose-adjusted propofol is recommended for these patients during the induction of anesthesia. However, for patients aged 75 years and over, established guidelines for propofol induction doses do not provide dose references. To this end, we observed 80 surgical patients (female 39, male 41, American Society of Anesthesiologists physical status score I ∼ II) to access the appropriate dose of propofol for inducing loss of consciousness (LOC). Accordingly, patients were subdivided into group A (20 patients, 45-64 years), group B (20 patients, 65-74 years), group C (20 patients, 75-84 years), and group D (20 patients, ≥ 85 years). All patients received propofol (at a rate of 0.3 mg/kg/min) alone for inducing LOC, which was defined by loss of both eyelash reflex and verbal response. Compared with group A, the propofol requirement for LOC in Group B, C and D decreased by 14.8, 25.2 and 38.5%, respectively. Bivariate linear correlation analysis showed that propofol requirement was negatively correlated with age. After adjusting for potential confounders, age was still an independent factor affecting propofol requirement. In conclusion, the propofol requirement for inducing LOC decreased significantly in elderly patients. We demonstrated that age was an independent factor impacting propofol requirement for LOC during the induction of general anesthesia, implying that the propofol dose for anesthesia induction should be further reduced in elderly surgical patients, especially those aged 75 years and over., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Deng, Chen, Tang, Deng, Lu and Song.)

Aims: Propofol may result in hypotension, bradycardia and loss of protective reflexes, especially in elderly patients, while esketamine, a N-methyl-D-aspartate receptor antagonist, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC 50 ) of propofol and coadministration is less likely to produce hypotension during gastrointestinal endoscopy in elderly patients., Methods: Ninety elderly patients, aged 65-89 years, undergoing gastrointestinal endoscopy were randomly assigned into 3 groups: SK0 (control) group (0 mg/kg esketamine); SK0.25 group (0.25 mg/kg esketamine); and SK0.5 group (0.5 mg/kg esketamine). Anaesthesia was achieved by plasma target-controlled infusion of propofol with different bolus doses of esketamine. The EC 50 of propofol for gastrointestinal endoscopy was determined by using the up-and-down method of Dixon. The initial plasma target concentration is 2.5 μg/mL and the adjacent concentration gradient is 0.5 μg/mL. Cardiovascular variables were also measured., Results: Propofol EC 50 s and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 3.69 (2.59-4.78), 2.45 (1.85-3.05) and 1.71 (1.15-2.27) μg/mL in the SK0, SK0.25 and SK0.5 groups, respectively (P < .05). The average percent change from baseline mean arterial pressure was -19.7 (7.55), -15.2 (7.14) and -10.1 (6.73), in the SK0, SK0.25 and SK0.5 groups, respectively (P < .001)., Conclusion: Combination medication of propofol with esketamine reduced the propofol EC 50 during gastrointestinal endoscopy in elderly patients compared with administration of propofol without esketamine. Increasing doses of SK with propofol are less likely to produce hypotension with shorter recovery time., (© 2021 British Pharmacological Society.)

Background: It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients., Methods/design: The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached., Discussion: Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100043585 . Registered on 23 February 2021., (© 2022. The Author(s).)

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.

Trehalose-6-phosphate synthase (TPS) plays an important role in the synthesis of trehalose. In the current study, a TPS gene was obtained from Diaphorina citri , and named as DcTPS1 which encoded a protein of 833 amino acid residues. Real-time quantitative PCR (qPCR) analysis revealed that DcTPS1 had the highest expression level in the midgut and fifth-instar nymph stage. Knockdown of DcTPS1 by RNA interference (RNAi) induced an abnormal phenotype and increased mortality and malformation rate with a decreased molting rate. In addition, silencing of DcTPS1 significantly inhibited D. citri chitin metabolism and fatty acid metabolism, while the expression levels of fatty acid decomposition-related genes were downregulated. Furthermore, comparative transcriptomics analysis revealed that 791 differentially expressed genes (DEGs) were upregulated and 678 DEGs were downregulated when comparing ds DcTPS1 groups with ds GFP groups. Bioinformatics analysis showed that upregulated DEGs were mainly involved in oxidative phosphorylation, whereas downregulated DEGs were mainly attributed to the lysosome and ribosome. These results indicated that DcTPS1 played an important role in the growth and development of D. citri .

The importance of astrocytes in behavior control is increasingly appreciated, but little is known about the effects of their dynamic activity in regulating learning and memory. In the present study, we constructed AAVs of photoactivatable and photoinactivatable Ras-related C3 botulinum toxin substrate 1 (Rac1) under the mGFAP promoter, which enabled the manipulation of Rac1 activity in astrocytes by optical stimulation in free-moving mice. We found that both up-regulation and down-regulation of astrocytic Rac1 activity in the basolateral amygdala (BLA) attenuated memory acquisition in a fear conditioning mouse model. Meanwhile, neuronal activation in the BLA induced by memory acquisition was inhibited under both the up- and down-regulation of astrocytic Rac1 activity during training. In terms of the impact on fear memory retrieval, we found both up- and down-regulation of BLA astrocytic Rac1 activity impaired memory retrieval of fear conditioning and memory retrieval-induced neuronal activation. Notably, the effect of astrocytic Rac1 on memory retrieval was reversible. Our results demonstrate that the normal activity of astrocytic Rac1 is necessary for the activation of neurons and memory formation. Both activation and inactivation of astrocytic Rac1 activity in the BLA reduced the excitability of neurons, and thereby impaired fear memory acquisition and retrieval., (© 2021. Center for Excellence in Brain Science and Intelligence Technology, CAS.)

Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People's Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.

Background: Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC., Methods: A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients' overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003-2008) and second (2009-2014) 6-year periods., Results: Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38-0.53, and HR 0.52, 95% CI 0.44-0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78-0.97, and HR 0.81, 95% CI 0.70-0.95)., Conclusion: Surveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.

Norepinephrine (NE) is often administered during the perioperative period of liver transplantation to address hemodynamic instability and to improve organ perfusion and oxygen supply. However, its role and safety profile have yet to be evaluated in pediatric living donor liver transplantation (LDLT). We hypothesized that intraoperative NE infusion might affect pediatric LDLT outcomes. A retrospective study of 430 pediatric patients (median [interquartile range] age, 7 [6.10] months; 189 [43.9%] female) receiving LDLT between 2014 and 2016 at Renji Hospital was conducted. We evaluated patient survival among recipients who received intraoperative NE infusion (NE group, 85 recipients) and those that did not (non-NE group, 345 recipients). The number of children aged over 24 months and weighing more than 10 kg in NE group was more than that in non-NE group. And children in NE group had longer operative time, longer anhepatic phase time and more fluid infusion. After multivariate regression analysis and propensity score regression adjusting for confounding factors to determine the influence of intraoperative NE infusion on patient survival, the NE group had a 169% more probability of dying. Although there was no difference in mean arterial pressure changes relative to the baseline between the two groups, we did observe increased heart rates in NE group compared with those of the non-NE group at anhepatic phase (P=0.025), neohepatic phase (P=0.012) and operation end phase (P=0.017) of the operation. In conclusion, intraoperative NE infusion was associated with a poorer prognosis for pediatric LDLT recipients. Therefore, we recommend the application of NE during pediatric LDLT should be carefully re-considered., (Copyright © 2020 Chen, Chen, Qi, Pan, Lu, Zhang, Zhu, Yu, Song and Lu.)

Guided bone regeneration (GBR) is an effective alveolar ridge reconstruction technique used before or at implant placement. The combination of various barrier membranes and bone substitutes has been employed. This study aimed to perform a preliminarily evaluation of the safety and performance of a new nonabsorbable bi-layered porous polyethylene (PPE) membrane, in combination with a freeze-dried cortical bone allograft in posterior mandibular ridge augmentation. Fifteen adults who had combined posterior mandibular defects were included for ridge augmentation via GBR using PPE membrane and allograft before implant placement. The keratinized mucosa width (KW), ridge width (RW), ridge height (RH), distance from measurement matrix to bone (DMB), and horizontal alveolar width at 14.0 mm apical to the occlusal plane (HAW) were clinically measured at 15 intended implant sites before and after the augmentation. Fifteen biopsy specimens were harvested at the implant sites for histological analysis. All the subjects completed the whole study. The KW and RH showed minor gains by 0.2 ± 1.4 mm and 0.9 ± 2.3 mm respectively; however, no statistically significant differences were found between, before, and after the augmentation (P > 0.05). In contrast, the RW and HAW significantly increased by 4.8 ± 1.6 mm and 2.3 ± 1.7 mm, respectively, (P ≤ 0.001), while DMB significantly decreased by 1.0 ± 0.8 mm after treatment (P < 0.001). Histological analysis revealed that allograft underwent active bone remodeling. The PPE membrane was adequately safe and efficient to use with allograft in GBR for the reconstruction of combined ridge defects. Although some complications were observed, these were manageable and subsequently lead to successful implant placement for all the subjects. However, further randomized controlled trials are still needed to confirm these findings.

Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

Thrombocytopenia is a common complication of critical care patients. The rates of bleeding events and mortality are also significantly increased in critical care patients with thrombocytopenia. Therefore, the Critical Care Medicine Committee of Chinese People's Liberation Army (PLA) worked with Chinese Society of Laboratory Medicine, Chinese Medical Association to develop this consensus to provide guidance for clinical practice. The consensus includes five sections and 27 items: the definition of thrombocytopenia, etiology and pathophysiology, diagnosis and differential diagnosis, treatment and prevention.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), is an important transmission vector of the citrus greening disease C andidatus Liberibacter asiaticus ( C Las). The D. citri midgut exhibits an important tissue barrier against C Las infection. However, the molecular mechanism of the midgut response to C Las infection has not been comprehensively elucidated. In this study, we identified 778 differentially expressed genes (DEGs) in the midgut upon CLas infection, by comparative transcriptome analyses, including 499 upregulated DEGs and 279 downregulated DEGs. Functional annotation analysis showed that these DEGs were associated with ubiquitination, the immune response, the ribosome, endocytosis, the cytoskeleton and insecticide resistance. KEGG enrichment analysis revealed that most of the DEGs were primarily involved in endocytosis and the ribosome. A total of fourteen DEG functions were further validated by reverse transcription quantitative PCR (RT-qPCR). This study will contribute to our understanding of the molecular interaction between CLas and D. citri., Competing Interests: The authors declare no conflict of interest.

Purpose: We aimed to investigate histogram analysis of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) to distinguish between deep myometrial invasion and superficial myometrial invasion in endometrial carcinoma (EC)., Methods: A total of 118 pathologically confirmed EC patients with preoperative DWI were included. The data were postprocessed with a DKI (b value of 0, 700, 1400, and 2000 s/mm2) model for quantitation of apparent diffusion values (D) and apparent kurtosis coefficient values (K) for non-Gaussian distribution. The apparent diffusion coefficient (ADC) was postprocessed with a conventional DWI model (b values of 0 and 800 s/mm2). A whole-tumor analysis approach was used. Comparisons of the histogram parameters of D, K, and ADC were carried out for the deep myometrial invasion and superficial myometrial invasion subgroups. Diagnostic performance of the imaging parameters was assessed., Results: The Dmean, D10th, and D90th in deep myometrial invasion group were significantly lower than those in superficial invasion group (P < 0.001, P < 0.001, and P = 0.023, respectively), as well as the ADCmean, ADC10th, and ADC90th (P = 0.001, P = 0.001, and P = 0.042, respectively). The Kmean and K90th were significantly higher in deep invasion group than those in superficial myometrial invasion group (P = 0.002 and P = 0.026, respectively). The D10th, Kmean, and ADC10th had a relatively higher area under the curve (AUC) (0.72, 0.66, and 0.71, respectively) than other parameters for distinguishing deep myometrial invasion of EC. D10th showed a relatively higher AUC than ADC10th for the differentiation of lesions with deep myometrial invasion from those with superficial myometrial invasion (0.72 vs. 0.71), but the variation was not statistically significant (P = 0.35)., Conclusion: Distribution of DKI and conventional DWI parameters characterized by histogram analysis may represent an indicator for deep myometrial invasion in EC. Both DKI and DWI models showed relatively equivalent effectiveness.

Heat stroke (HS) is a fatal disease caused by thermal damage in the body, and it has a very high mortality rate. In 2015, the People's Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China, Expert consensus on standardized diagnosis and treatment for heat stroke. With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years, the 2015 consensus no longer meet the requirements for HS prevention and treatment. It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage, is more practical and is more in line with China's national conditions. This new expert consensus includes new concept of HS, recommendations for laboratory tests and auxiliary examinations, new understanding of diagnosis and differential diagnosis, On-site emergency treatment and In-hospital treatment, translocation of HS patients and prevention of HS.

Rationale: We studied the feasibility of total arathyroidectomy(tPTX)+multi-point transplantation in the forearm for treatment of secondary hyperparathyroidism. Considering the controversial nature of the appropriate timing for and location of this type of surgery, relevant research is relatively rare. Our experience may be a relatively successful one., Patient Concerns: Our patient was a 28-year-old woman with end-stage renal disease (ESRD), who was on dialysis for 7 years, and a 2-year history of progressively aggravated bone pain. She also had hypercalcemia and hyperphosphatemia., Diagnoses: Given the patient's history of long-term dialysis, bone pain, high levels of intact parathyroid hormone(i-PTH) and hypercalcemia, we performed ultrasonography which showed solid nodules in the bilateral parathyroid glands. She was accordingly diagnosed with SHPT., Interventions: The patient underwent tPTX+multi-point subcutaneous transplantation in the forearm., Outcomes: Her i-PTH level dropped to < 300 pg/mL, and the symptoms of bone pain markedly reduced after surgery., Lessons: Total parathyroidectomy+multi-point subcutaneous transplantation in the forearm may be a reliable surgical approach for patients with ESRD.

Purpose: To evaluate agreement between eye banks (EBs) and a reading center on endothelial cell density (ECD) determinations in the Cornea Preservation Time Study., Methods: The Cornea Image Analysis Reading Center (CIARC) performed variable frame image analysis on EB-obtained-preoperative central endothelial images (after lamellar dissection for Descemet stripping automated endothelial keratoplasty by the EBs or before shipping, if surgeon prepared) to determine ECD. The EBs performed their usual method of ECD determination. The CIARC and EBs also provided ECD determinations from screening central endothelial images taken by the EBs during donor evaluation. Two independent masked CIARC readers determined ECD with measurements averaged., Results: The mean preoperative ECD was 15 cells/mm greater by the EBs than by CIARC (N = 1286, P < 0.001) with 95% limits of agreement of (-644, 675 cells/mm). The limits of agreement in preoperative ECD were wider in the After-Lamellar-Dissection Group (-687, 683 cells/mm) than in the Before Shipping Group [(-505, 633 cells/mm); P = 0.03]. The EBs-determined preoperative ECD was within 10% of the CIARC-determined ECD for 886 (69%) image sets, with 236 (18%) higher by >10% and 164 (13%) lower by >10%. Excellent agreement appeared between the EBs and CIARC when 100-300 cells could be analyzed in contrast to <100 cells (SD = 308 cells/mm vs. SD = 603 cells/mm; P < 0.001)., Conclusions: The mean ECD by the EBs and CIARC were similar, but there was considerable variability between determinations for individual corneas. Agreement improved between the 2 measurements when more than 100 cells were able to be analyzed.

Background: Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold., Aims: To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF., Methods: Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A -/- ) mice 21 days after intratracheal administration of bleomycin (BLM)., Results: HSV1 infection caused acute exacerbation in mice with BLM-induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)-related proteins in mice with BLM-induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL-17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE-IPF. Compared with WT mice with BLM+HSV1, IL-17A -/- mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response., Conclusions: HSV1 infection in addition to BLM-induced IPF can successfully establish AE-IPF in mice. IL-17A and ERS promote lung inflammation in AE-IPF development., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aim: To determine whether dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters increase the detectability of MRI-invisible residual cervical cancer after conisation., Materials and Methods: This retrospective study included 59 patients with MRI-invisible cervical cancer, but positive conisation pathology. Thirty-five patients were confirmed to have residual cervical cancer, and 24 patients showed non-residual cervical cancer. DCE-MRI quantitative parameters were calculated in the anterior or posterior cervix according to the conisation position. Receiver operating characteristic (ROC) analysis was used to find the threshold of DCE-MRI parameters in differentiate residual cervical cancer patients from non-residual cervical cancer patients after conisation., Results: For patients with residual cervical cancer, the K trans and V e values were significantly higher than in their counterparts with non-residual cervical cancer (0.610±0.395 versus 0.366±0.305/min, p=0.013; and 0.703±0.270 versus 0.540±0.280%, p=0.028; respectively). The K trans showed the highest area under the ROC curve (AUC) of 0.705 (p=0.004) with a sensitivity of 67.6% and specificity of 68%., Conclusion: DCE-MRI quantitative parameters increased the detectability of MRI-invisible residual cervical cancer after conisation., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Azithromycin (AZM), that is a macrolide antibiotic, has been found to treat diffuse panbronchiolitis (DPB) effectively. However, the mechanism of action underlying the therapeutic effects remains unclear. We selected 64 patients with DPB from 305 patients who were diagnosed with DPB at the outpatient clinic in Shanghai Pulmonary Hospital from Jan 2010 to Oct 2014. The primary PBLs, CD4 + T cells, and Jurkat T cells were treated with AZM or erythromycin (EM), and the effects of AZM and EM on IL-17A and CXCL-2 production, proliferation, apoptosis and autophagy were evaluated. AZM and EM significantly inhibited IL-17A and CXCL-2 production in patients' PBLs (all P < 0.05). AZM significantly inhibited proliferation and promoted apoptosis of T cells from DPB patients. AZM can enhance autophagosome formation of T cells by suppressing S6RP phosphorylation, which is a downstream target of mTOR pathway (all P < 0.05). AZM and EM significantly decreased secreted IL-17A levels (P < 0.05) in the primary CD4 + T cells of patients with DPB. AZM may treat DPB patients by targeting cytokine production, proliferation, apoptosis and autophagy of T cell. The mechanism of therapeutic effects of AZM on DPB may be associated with a specific inhibition of mTOR pathway in the T lymphocytes., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Recently published studies suggest that the anaesthetic technique used during oncologic surgery can improve patient outcomes. Therefore, the authors evaluated the survival of patients with resected colorectal carcinoma liver metastases (CRCLMs) who received either EGA (general anaesthesia [GA] combined with epidural anaesthesia [EA]) or GA alone. Methods: We conducted an ambispective cohort study including 225 post-surgical CRCLM patients between May 2007 and July 2012 and performed a follow-up investigation of survival in July 2017. Results: The basic characteristics in the two groups were largely similar. The median (quartiles) recurrence interval for all patients was 10 (2.5, 23) months, and the median (quartiles) survival for CRCLM patients post-surgically was 37 (30.5, 51.5) months. Perioperative EA was associated with survival (P =0.039, log-rank test), with an estimated hazard ratio of 0.737 (95% CI 0.551-0.985) in the univariate analysis. Kaplan-Meier estimates of survival for GA and EGA suggested that GA might provide better outcomes than EGA [P=0.028, hazard ratio of 0.7328 (95% CI 0.5433-0.9884)]. Significant differences in anaesthesia techniques were found (P=0.048), with an adjusted estimated hazard ratio of 0.741 (95% CI 0.550-0.998) in the multivariate analysis. Subgroup analyses of patients in different age groups (< 40, ≥ 40 but <60, and ≥ 60 years old) suggested that no significant differences existed among all three subgroups. Conclusions: Compared with EGA, GA may provide a better survival outcome for CRCLM patients. The benefits of anaesthetic techniques in oncological surgery are most likely related to certain cancer types., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.