Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common stroke type with high morbidity and mortality. There are mainly three surgical methods for treating ICH. Unfortunately, thus far, no specific surgical method has been proven to be the most effective. We carried out this study to investigate whether minimally invasive surgeries with endoscopic surgery or stereotactic aspiration (frameless navigated aspiration) will improve functional outcomes in patients with supratentorial ICH compared with small-bone flap craniotomy. METHODS: In this parallel-group multicenter randomized controlled trial conducted at 16 centers, patients with supratentorial hypertensive ICH were randomized to receive endoscopic surgery, stereotactic aspiration, or craniotomy at a 1:1:1 ratio from July 2016 to June 2022. The follow-up duration was 6 months. Patients were randomized to receive endoscopic evacuation, stereotactic aspiration, or small-bone flap craniotomy. The primary outcome was favorable functional outcome, defined as the proportion of patients who achieved a modified Rankin scale (mRS) score of 0-2 at the 6-month follow-up. RESULTS: A total of 733 patients were randomly allocated to three groups: 243 to the endoscopy group, 247 to the aspiration group, and 243 to the craniotomy group. Finally, 721 patients (239 in the endoscopy group, 246 in the aspiration group, and 236 in the craniotomy group) received treatment and were included in the intention-to-treat analysis. Primary efficacy analysis revealed that 73 of 219 (33.3%) in the endoscopy group, 72 of 220 (32.7%) in the aspiration group, and 47 of 212 (22.2%) in the craniotomy group achieved favorable functional outcome at the 6-month follow-up (P = .017). We got similar results in subgroup analysis of deep hemorrhages, while in lobar hemorrhages the prognostic outcome was similar among three groups. Old age, deep hematoma location, large hematoma volume, low preoperative GCS score, craniotomy, and intracranial infection were associated with greater odds of unfavorable outcomes. The mean hospitalization expenses were ¥92,420 in the endoscopy group, ¥77,351 in the aspiration group, and ¥100,947 in the craniotomy group (P = .000). CONCLUSIONS: Compared with small bone flap craniotomy, endoscopic surgery and stereotactic aspiration improved the long-term outcome of hypertensive ICH, especially deep hemorrhages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811614.

Vacuum Evaporation Plating Enabling ≤ 10 µm Ultrathin Lithium Foils for Lithium Metal Batteries.

Lithium (Li) metal is widely recognized as a viable candidate for anode material in future battery technologies due to its exceptional energy density. Nevertheless, the commercial Li foils in common use are too thick (≈100 µm), resulting in a waste of Li resources. Herein, by applying the vacuum evaporation plating technology, the ultra-thin Li foils (VELi) with high purity, strong adhesion, and thickness of less than 10 µm are successfully prepared. The manipulation of evaporation temperature allows for convenient regulation of the thickness of the fabricated Li film. This physical thinning method allows for fast, continuous, and highly accurate mass production. With a current density of 0.5 mA cm-2 for a plating amount of 0.5 mAh cm-2, VELi||VELi cells can stably cycle for 200 h. The maximum utilization of Li is already more than 25%. Furthermore, LiFePO4||VELi full cells present excellent cycling performance at 1 C (1 C = 155 mAh g-1) with a capacity retention rate of 90.56% after 240 cycles. VELi increases the utilization of active Li and significantly reduces the cost of Li usage while ensuring anode cycling and multiplication performance. Vacuum evaporation plating technology provides a feasible strategy for the practical application of ultra-thin Li anodes.

Phosphine-Catalyzed [4 + 1] Annulation of ß'-Acetoxy Allenoate with α-Alkylidene Succinimides: Access to Functionalized Spirosuccinimide Derivatives.

A phosphine-catalyzed [4 + 1] annulation of ß'-acetoxy allenoate with α-alkylidene succinimides is described. This method demonstrates the nucleophilic dialkylation and cyclization of α-alkylidene succinimides, resulting in the formation of functionalized spirosuccinimide derivatives. The reaction exhibits a wide substrate scope and yields ranging from moderate to excellent under the optimized conditions. In addition, the biological evaluation indicates that the cycloadduct 3u presents satisfied inhibitory activities for three human cancer cell lines (HCT116, A549, and HepG2).

CACNA1B protects naked mole-rat hippocampal neuron from apoptosis via altering the subcellular localization of Nrf2 after 60Co irradiation.

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation-induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next-generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation-induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation.

Spray-lithography of hybrid graphene-perovskite paper-based photodetectors for sustainable electronics.

Paper is an ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems. When combined with nanomaterial-based devices, it can be harnessed for various Internet-of-Things applications, ranging from wearable electronics to smart packaging. However, paper remains a challenging substrate for electronics due to its rough and porous nature. In addition, the absence of established fabrication methods is impeding its utilization in wearable applications. Unlike other paper-based electronics with added layers, in this study, we present a scalable spray-lithography on a commercial paper substrate. We present a non-vacuum spray-lithography of chemical vapor deposition (CVD) single-layer graphene (SLG), carbon nanotubes (CNTs) and perovskite quantum dots (QDs) on a paper substrate. This approach combines the advantages of two large-area techniques: CVD and spray-coating. The first technique allows for the growth of SLG, while the second enables the spray coating of a mask to pattern CVD SLG, electrodes (CNTs), and photoactive (QDs) layers. We harness the advantages of perovskite QDs in photodetection, leveraging their strong absorption coefficients. Integrating them with the graphene enhances the photoconductive gain mechanism, leading to high external responsivity. The presented device shows high external responsivity of ∼520 A W-1at 405 nm at <1 V bias due to the photoconductive gain mechanism. The prepared paper-based photodetectors (PDs) achieve an external responsivity of 520 A W-1under 405 nm illumination at <1 V operating voltage. To the best of our knowledge, our devices have the highest external responsivity among paper-based PDs. By fabricating arrays of PDs on a paper substrate in the air, this work highlights the potential of this scalable approach for enabling ubiquitous electronics on paper.

Mechanisms of intermittent theta-burst stimulation attenuating nerve injury after ischemic reperfusion in rats through endoplasmic reticulum stress and ferroptosis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) exerts neuroprotective effects early in cerebral ischemia/reperfusion (I/R) injury. Intermittent theta-brust stimulation (iTBS), a more time-efficient modality of rTMS, improves the efficiency without at least decreasing the efficacy of the therapy. iTBS elevates cortical excitability, and in recent years it has become increasingly common to apply iTBS to patients in the early post-IS period. However, little is known about the neuroprotective mechanisms of iTBS. Endoplasmic reticulum stress (ERS), and ferroptosis have been shown to be involved in the development of I/R injury. We aimed to investigate the potential regulatory mechanisms by which iTBS attenuates neurological injury after I/R in rats. METHODS: Rats were randomly divided into three groups: sham-operated group, MCAO/R group, and MCAO/R + iTBS group, and were stimulated with iTBS 36 h after undergoing middle cerebral artery occlusion (MCAO) or sham-operated. The expression of ERS, ferroptosis, and apoptosis-related markers was subsequently detected by western blot assays. We also investigated the mechanism by which iTBS attenuates nerve injury after ischemic reperfusion in rats by using the modified Neurological Severity Score (mNSS) and the balance beam test to measure nerve function. RESULTS: iTBS performed early in I/R injury attenuated the levels of ERS, ferroptosis, and apoptosis, and improved neurological function, including mNSS and balance beam experiments. It is suggested that this mode of stimulation reduces the cost per treatment by several times without compromising the efficacy of the treatment and could be a practical and less costly intervention.

Applications of Functional Near-Infrared Spectroscopy (fNIRS) Neuroimaging During Rehabilitation Following Stroke: A Review.

Stroke is a cerebrovascular disease that impairs blood supply to localized brain tissue regions due to various causes. This leads to ischemic and hypoxic lesions, necrosis of the brain tissue, and a variety of functional disorders. Abnormal cortical activation and functional connectivity occur in the brain after a stroke, but the activation patterns and functional reorganization are not well understood. Rehabilitation interventions can enhance functional recovery in stroke patients. However, clinicians require objective measures to support their practice, as outcome measures for functional recovery are based on scale scores. Furthermore, the most effective rehabilitation measures for treating patients are yet to be investigated. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging method that detects changes in cerebral hemodynamics during task performance. It is widely used in neurological research and clinical practice due to its safety, portability, high motion tolerance, and low cost. This paper briefly introduces the imaging principle and the advantages and disadvantages of fNIRS to summarize the application of fNIRS in post-stroke rehabilitation.

A patient-specific, interactive, multiuser, online mixed-reality neurosurgical training and planning system.

OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.

Study of Combined Effect of Bacteriophage vB3530 and Chlorhexidine on the Inactivation of Pseudomonas aeruginosa.

BACKGROUND: Chlorhexidine (CHG) is a disinfectant commonly used in hospitals. However, it has been reported that the excessive use of CHG can cause resistance in bacteria to this agent and even to other clinical antibiotics. Therefore, new methods are needed to alleviate the development of CHG tolerance and reduce its dosage. This study aimed to explore the synergistic effects of CHG in combination with bacteriophage against CHG-tolerant Pseudomonas aeruginosa (P. aeruginosa) and provide ideas for optimizing disinfection strategies in clinical environments as well as for the efficient use of disinfectants. METHODS: The CHG-tolerant P. aeruginosa strains were isolated from the First Affiliated Hospital of Wenzhou Medical University in China. The bacteriophage vB3530 was isolated from the sewage inlet of the hospital, and its genome was sequenced. Time-killing curve was used to determine the antibacterial effects of vB3530 and chlorohexidine gluconate (CHG). The phage sensitivity to 16 CHG-tolerant P. aeruginosa strains and PAO1 strain was detected using plaque assay. The emergence rate of resistant bacterial strains was detected to determine the development of phage-resistant and CHG-tolerant strains. Finally, the disinfection effects of the disinfectant and phage combination on the surface of the medical devices were preliminarily evaluated. RESULTS: The results showed that (1) CHG combined with bacteriophage vB3530 significantly inhibited the growth of CHG-resistant P. aeruginosa and reduced the bacterial colony forming units (CFUs) after 24 h. (2) The combination of CHG and bacteriophage inhibited the emergence of phage-resistant and CHG-tolerant strains. (3) The combination of CHG and bacteriophage significantly reduced the bacterial load on the surface of medical devices. CONCLUSIONS: In this study, the combination of bacteriophage vB3530 and CHG presented a combined inactivation effect to CHG-tolerant P. aeruginosa and reduced the emergence of strains resistant to CHG and phage. This study demonstrated the potential of bacteriophage as adjuvants to traditional disinfectants. The use of bacteriophage in combination with commercial disinfectants might be a promising method for controlling the spread of bacteria in hospitals.

A newly isolated bacteriophage vB8388 and its synergistic effect with aminoglycosides against multi-drug resistant Klebsiella oxytoca strain FK-8388.

The bacteriophage vB8388 can lyse multi-drug resistant Klebsiella oxytoca strain FK-8388 and maintain stability in a wide range of temperatures (from 4 °C to 80 °C) and pHs (3-11). Bioinformatics analysis showed that vB8388 is a linear double-stranded DNA virus that is 39,750 long with 50.65% G + C content and 44 putative open reading frames (ORFs). Phage vB8388 belongs to the family Autographviridae and possesses a non-contractile tail. The latency period of vB8388 was approximately 20 min. The combination of phage vB8388 and gentamicin, amikacin, or tobramycin could effectively inhibit the growth of K. oxytoca strain FK-8388, with a decrease of more than 4 log units within 12 h in vitro. Phage vB8388 showed a strong synergistic effect with gentamicin that could enhance the anti-biofilm effect of vB8388. The phage + gentamicin combination also showed synergy in vivo in the larval infection model of Galleria mellonella. In conclusion, the findings of this study suggest the potential of phage + antibiotic combination therapy to be used as an alternative therapeutic approach for treating infectious diseases caused by multidrug-resistant bacteria.

Emerging roles of leptin in Parkinson's disease: Chronic inflammation, neuroprotection and more?

An increasing body of experimental evidence implicates a relationship between immunometabolic deterioration and the progression of Parkinson's disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by circulating adipokines, in particular leptin. We screened the current literature on the role of adipokines in PD. Hence, we searched known databases (PubMed, MEDLINE/OVID) and reviewed original and review articles using the following terms: "leptin/ObR", "Parkinson's disease", "immune-metabolism", "biomarkers" and "neuroinflammation". Focusing on leptin, we summarize and discuss the existing in vivo and in vitro evidence on how adipokines may be protective against neurodegeneration, but at the same time contribute to the progression of PD. These components of the adipose brain axis represent a hitherto underestimated pathway to study systemic influences on dopaminergic degeneration. In addition, we give a comprehensive update on the potential of adjunctive therapeutics in PD targeting leptin, leptin-receptors, and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanisms of action and the value of central and peripheral adipose-immune-metabolism molecular phenotyping in order to develop and validate the differential roles of different adipokines as potential therapeutic target for PD patients.

Ureterocele with duplex collecting systems and febrile urinary tract infection risk.

PURPOSE: Ureterocele has been hypothesized to be the risk factor for febrile urinary tract infections (F-UTIs) in patients with duplex collecting systems, but this has not been proved, and our goal was to assess the relation between ureterocele with duplex collecting systems and F-UTIs. METHODS: We included individual-participant data from patients seen for complicated duplex collecting systems from 2010 to 2020 retrospectively followed. Those with using continuous low-dose antibiotic prophylaxis and incompletely duplicated systems were removed from the study. The participants were divided into two cohorts according to patients with or without ureterocele. The primary endpoint of this study was recurrent F-UTIs. RESULTS: We analyzed medical reports of 300 patients, of which 75% were female. Among the 300 patients, F-UTIs developed in 111/159 (69.8%) patients in the ureterocele group and in 69/141 (48.9%) patients in the no-ureterocele group. Univariate analysis found no discernible difference except in grade of hydronephrosis between ureterocele group and no-ureterocele group. Moreover, Cox proportional regression analysis revealed that patients of duplex system ureterocele might be intrinsically more prone to develop F-UTIs (adjusted hazard ratio 1.894; 95% CI 1.412-2.542; p  <  0.001). CONCLUSION: Among participants with duplex systems, the risk of recurrent F-UTIs in patients with ureterocele was higher than patients without it, and mini-invasive surgical correction should be considered at young age to reduce F-UTIs.

Rapid ResaCeftazidime-Avibactam Enterobacterales NP Test: Rapid Detection of Ceftazidime-Avibactam Susceptibility in Enterobacterales.

Ceftazidime-avibactam (CZA), a novel ß-lactam/ß-lactamase inhibitor combination, has good antibacterial activity against carbapenem-resistant Enterobacterales (CRE) producing class A and C and some class D carbapenemases, but in recent years, the emergence of CZA-resistant Enterobacterales bacteria is growing. Therefore, rapid, accurate, and timely detection of CZA is necessary for clinical anti-infection treatment. In this study, the rapid ResaCeftazidime-avibactam Enterobacterales NP test was developed; its principle is that metabolically active bacteria (CZA-resistant strains) can change resazurin-PrestoBlue, a viability colorant, from blue to purple or pink in the presence of CZA, whereas CZA-susceptible strains cannot. We used 178 Enterobacterales isolates to evaluate the performance of this test. This test allowed the susceptibility of Enterobacterales to CZA to be detected within 4.5 h with an overall performance of 96% category agreement (CA), 7% major errors (MEs), and 0% very major errors (VMEs). Performance for Escherichia coli included 100% CA and 0% MEs and VMEs. Performance for Klebsiella pneumoniae included 99% CA and 2% MEs and 0% VMEs. Performance for Enterobacter cloacae included 87% CA, 25% MEs, and 0% VMEs. Moreover, this test is both economical ($1.0106 per isolate) and convenient, as it only requires basic laboratory equipment. In a word, the rapid ResaCeftazidime-avibactam Enterobacterales NP test is rapid and feasible, which may provide certain backing for the rapid screening and timely treatment of CZA-resistant strains in the clinic.

The identification of phage vB_1086 of multidrug-resistant Klebsiella pneumoniae and its synergistic effects with ceftriaxone.

BACKGROUND: The continued rise of Klebsiella pneumoniae resistance to antibiotics is precipitating a medical crisis. Bacteriophages have been hailed as one possible therapeutic option to enhance the efficacy of antibiotics. This study describes the genomic characterization and biological property of a new bacteriophage vB_1086 and its potential for phage therapy application against Klebsiella pneumoniae. METHODS: In our study, the double-layer agar plate method isolated a lytic bacteriophage named vB_1086. Besides, we analyzed its biological characteristics and genetic background. Then the antibacterial ability of the bacteriophage vB_1086 combined with antibiotics were analyzed by the combined checkerboard method. The impact on the formation of biofilms was analyzed by crystal violet staining method. RESULTS: vB_1086 is a lytic bacteriophage with stable biological characteristics and clear genetic background, showing good antibacterial activity in combination with ceftriaxone, and the combination of phage and meropenem can effectively inhibit the formation of biofilm. Besides, the combination of bacteriophage and antimicrobials can effectively alleviate the generation of bacterial resistance and reduce the dosage of antimicrobials. CONCLUSION: vB_1086 is a novel phage. To some extent, these results provide valuable information that phage vB_1086 can be combined with antibiotics to reduce the dosage of antimicrobials and alleviate the generation of bacterial resistance.

A comparison of the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses.

PURPOSE: To compare the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses. METHODS: The clinical characteristics corresponding to pediatric urolithiasis patients that had undergone exome sequencing at our hospital between January 2016 and May 2021 were collected. Genetic analysis results were used to separate patients into positive and negative molecular diagnosis groups. Multivariate logistic regression analyses adjusted for visiting age, sex, ethnicity, province, and body mass index were used to compare differences in medical history, diagnostic imaging findings, and renal function between individuals with and without molecular diagnoses. RESULTS: In total, 194 patients with pediatric urolithiasis of unknown etiology underwent exome sequencing and were included in the present study, of whom 63 obtained urolithiasis-related molecular diagnoses. Relative to cases without a molecular diagnosis, those with a positive molecular diagnosis were more likely to be associated with a positive family history (OR 2.84, 95% CI 1.29-6.29, p = 0.008), consanguineous parents (OR 24.7, 95% CI 1.34-454, p = 0.002), early onset (OR 1.26, 95% CI 1.09-1.45, p < 0.001), nephrocalcinosis (OR 10.6, 95% CI 3.06-36.6, p < 0.001), cast stone (OR 18.9, 95% CI 4.40-81.1, p < 0.001), multiple stones (OR 13.9, 95% CI 6.39-30.2, p < 0.001), bilateral stones (OR 7.04, 95% CI 3.47-14.2, p < 0.001), a lower estimated glomerular filtration rate (OR 1.17, 95% CI 1.07-1.28, p < 0.001), and chronic kidney disease (OR 26.9, 95% CI 1.42-526, p < 0.001). CONCLUSION: A positive family history, consanguineous parents, early onset, nephrocalcinosis, severe stone burden, and impaired renal function are signals of concern that are suggestive of inherited urolithiasis.

Quantifying human mixing patterns in Chinese provinces outside Hubei after the 2020 lockdown was lifted.

BACKGROUND: Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic, the regular contact patterns of the population have been disrupted due to social distancing both imposed by the authorities and individual choices. Many studies have focused on age-mixing patterns before the COVID-19 pandemic, but they provide very little information about the mixing patterns in the COVID-19 era. In this study, we aim at quantifying human heterogeneous mixing patterns immediately after lockdowns implemented to contain COVID-19 spread in China were lifted. We also provide an illustrative example of how the collected mixing patterns can be used in a simulation study of SARS-CoV-2 transmission. METHODS AND RESULTS: In this work, a contact survey was conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a mathematical model of SARS-CoV-2 transmission. Study participants reported 2.3 contacts per day (IQR: 1.0-3.0) and the mean per-contact duration was 7.0 h (IQR: 1.0-10.0). No significant differences in average contact number and contact duration were observed between provinces, the number of recorded contacts did not show a clear trend by age, and most of the recorded contacts occurred with family members (about 78%). The simulation study highlights the importance of considering age-specific contact patterns to estimate the COVID-19 burden. CONCLUSIONS: Our findings suggest that, despite lockdowns were no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation.

Mobile internet-based mixed-reality interactive telecollaboration system for neurosurgical procedures: technical feasibility and clinical implementation.

OBJECTIVE: To increase access to health interventions and healthcare services for patients in resource-constrained settings, strategies such as telemedicine must be implemented for the allocation of medical resources across geographic boundaries. Telecollaboration is the dominant form of surgical telemedicine. In this study, the authors report and evaluate a novel mobile internet-based mixed-reality interactive telecollaboration (MIMIT) system as a new paradigm for telemedicine and validate its clinical feasibility. METHODS: The application of this system was demonstrated for long-distance, real-time collaboration of neuroendoscopic procedures. The system consists of a local video processing workstation, a head-mounted mixed-reality display device, and a mobile remote device, connected over mobile internet (4G or 5G), allowing global point-to-point communication. Using this system, 20 cases of neuroendoscopic surgery were performed and evaluated. The system setup, composite video latency, technical feasibility, clinical implementation, and future potential business model were analyzed and evaluated. RESULTS: The MIMIT system allows two surgeons to perform complex visual and verbal communication during the operation. The average video delay time is 184.25 msec (range 160-230 msec) with 4G mobile internet, and 23.25 msec (range 20-26 msec) with 5G mobile internet. Excellent image resolution enabled remote neurosurgeons to visualize all critical anatomical structures intraoperatively. Remote instructors could easily make marks on the surgical view; then the composite image, as well as the audio conversation, was transferred to the local surgeon. In this way, a real-time, long-distance collaboration can occur. This system was used for 20 neuroendoscopic surgeries in various cities in China and even across countries (Boston, Massachusetts, to Jingzhou, China). Its simplicity and practicality have been recognized by both parties, and there were no technically related complications recorded. CONCLUSIONS: The MIMIT system allows for real-time, long-distance telecollaborative neuroendoscopic procedures and surgical training through a commercially available and inexpensive system. It enables remote experts to implement real-time, long-distance intraoperative interaction to guide inexperienced local surgeons, thus integrating the best medical resources and possibly promoting both diagnosis and treatment. Moreover, it can popularize and improve neurosurgical endoscopy technology in more hospitals to benefit more patients, as well as more neurosurgeons.

Insulin for hyperglycemia prevention and management during postgastrectomy nutrition support in gastric cancer: Reduced complications in a retrospective cohort study in China.

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness of insulin addition to the total nutrition admixture (TNA) for glycemic control among patients with gastric cancer (GC) receiving supplementary parenteral nutrition (SPN) after gastrectomy. METHODS AND STUDY DESIGN: A retrospective cohort study was conducted among 208 noncritical ill patients who underwent gastrectomy for GC from 2017 to 2019 at a tertiary teaching hospital in Lanzhou, China. All the included patients received individualized SPN and enteral nutrition treatment after gastrectomy. The patients were randomly divided into insulin and noninsulin groups based on the TNA composition. Blood glucose (BG) measurements, glycemic fluctuation, and hypoglycemia incidence during SPN were compared between the two groups. The postoperative comprehensive complications index (CI) and infections were compared according to insulin regimen and postoperative glycemic status. RESULTS: The mean BG was significantly lower and fluctuated less in the insulin group than in the noninsulin group (p<0.05). One unit of insulin per 6 g of parenteral nutrition glucose addition to TNA did not increase hypoglycemia incidence (p>0.05). Comparing CI and the infection rate, no significance was observed between the insulin and noninsulin groups, but a higher postoperative CI was observed in patients with hyperglycemia than in euglycemic patients (p<0.05). CONCLUSIONS: Appropriate insulin addition to TNA has an overall positive effect on glycemic management in patients with noncritical GC who received SPN after gastrectomy. Postoperative glycemic status was associated with the incidence of relevant complications. Further research is needed for conclusive recommendations.

Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis.

PURPOSE: To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup. METHODS: A retrospective analysis of both metabolic and genomic data was performed for the first 105 pediatric urolithiasis patients who underwent exome sequencing at our hospital from February 2016 to October 2018. Measurements included the diagnostic yield of exome sequencing in the entire cohort and each metabolic subgroup (hyperoxaluria, hypocitraturia, hypercalciuria, hyperuricosuria and cystine stone subgroups). The conformity between molecular diagnoses and metabolic evaluation was also evaluated. RESULTS: The present study involved a cohort of 105 pediatric patients with urolithiasis, from which diagnostic variants were identified in 38 patients (36%), including 27 primary hyperoxaluria and 11 cystinuria. In the metabolic subgroup analyses, 41% hyperoxaluria cases were primary hyperoxaluria caused by monogenic defects, and 100% of the causes of cystine stones could be explained by monogenic defects. However, no appropriate inherited causes were identified for hypocitraturia, hypercalciuria, or hyperuricosuria in the cohort. A high conformity (100%) was obtained between the molecular diagnoses and metabolic evaluation. CONCLUSION: Exome sequencing in a cohort of 105 pediatric patients with urolithiasis yielded a genetic diagnosis in 36% of cases and the molecular diagnostic yield varies substantially across different metabolic abnormalities.

Design, synthesis, and biological evaluation of novel FXR agonists based on auraptene.

Farnesoid X receptor (FXR) has been considered as an attractive target for metabolic disorder and liver injury, while many current FXR agonists suffer from undesirable side effects, such as pruritus. Therefore, it is urgent to develop new structure types different from current FXR agonists. In this study, a series of structural optimizations were introduced to displace the unstable coumarin and geraniol scaffolds of auraptene (AUR), a novel and safe FXR agonist. All of these efforts led to the identification of compound 14, a potent FXR agonist with nearly fourfold higher activity than AUR. Molecular modeling study suggested that compound 14 fitted well with binding pocket, and formed the key ionic bond with His291 and Arg328. In acetaminophen-induced acute liver injury model, compound 14 exerts better therapeutic effect than that of AUR, which highlighting its pharmacological potential in the treatment of drug-induced liver injury.