The effect of sevoflurane exposure on cell-type-specific changes in the prefrontal cortex in young mice.

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia.

MRI versus Dual-Energy CT in Local-Regional Staging of Gastric Cancer.

Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.

Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Dexmedetomidine Infusion Versus Placebo During Light or Deep Anesthesia on Postoperative Delirium in Older Patients Undergoing Major Noncardiac Surgery: A Pilot Randomized Factorial Trial.

BACKGROUND: Postoperative delirium (POD) is common among older surgical patients and may be affected by dexmedetomidine and depth of anesthesia. We designed this pilot study to assess the feasibility of comparing dexmedetomidine with normal saline during light versus deep anesthesia on POD in older patients undergoing major noncardiac surgery. METHODS: In this pilot randomized factorial study, 80 patients aged 60 years or older undergoing major noncardiac surgery were randomized (1:1:1:1) to receive dexmedetomidine infusion 0.5 µg/kg/h or normal saline placebo during light (bispectral index [BIS] target 55) or deep (BIS target 40) anesthesia. Feasibility end points included consent rate and dropout rate, timely enrollment, blinded study drug administration throughout surgery, no inadvertent unmasking, achieving BIS target throughout >70% of surgery duration, and the process of twice-daily POD screening. In addition, we estimated the POD incidences in the 2 control groups (placebo and deep anesthesia) and treatment effects of dexmedetomidine and light anesthesia. RESULTS: Between November 1, 2021, and June 30, 2022, 78 patients completed the trial (mean [standard deviation, SD] age, 69.6 [4.6] years; 48 male patients [62%]; dexmedetomidine-deep, n = 19; dexmedetomidine-light, n = 20; placebo-deep, n = 19; placebo-light, n = 20). This study had a high consent rate (86%) and a low dropout rate (2.5%). Average recruitment was 5 patients at each center per month. Dexmedetomidine and normal saline were administered in a blinded fashion in all patients. Unmasking did not occur in either group. Approximately 99% of patients received the scheduled study drug infusion throughout the surgery. Approximately 81% of patients achieved the BIS targets throughout >70% of the surgery duration. The scheduled twice-daily POD screening was completed without exception. Overall, 10 of the 78 patients (13%; 95% confidence interval [CI], 7%-22%) developed POD. For the 2 reference groups, POD was observed in 7 of the 39 patients (17.9%; 95% CI, 9%-32.7%) in the placebo group and 7 of the 38 patients (18.4%; 95% CI, 9.2%-33.4%) in the deep anesthesia group. Regarding the treatment effects on POD, the estimated between-group difference was -10% (95% CI, -28% to 7%) for dexmedetomidine versus placebo, and -11% (95% CI, -28% to 6%) for light versus deep anesthesia. CONCLUSIONS: The findings of this pilot study demonstrate the feasibility of assessing dexmedetomidine versus placebo during light versus deep anesthesia on POD among older patients undergoing major noncardiac surgery, and justify a multicenter randomized factorial trial.

Utility of Combined Use of Imaging Features From Abdominopelvic CT and CA 125 to Identify Presence of CT Occult Peritoneal Metastases in Advanced Gastric Cancer.

OBJECTIVE: The purpose of this study is to identify the presence of occult peritoneal metastasis (OPM) in patients with advanced gastric cancer (AGC) by using clinical characteristics and abdominopelvic computed tomography (CT) features. METHODS: This retrospective study included 66 patients with OPM and 111 patients without peritoneal metastasis (non-PM [NPM]) who underwent preoperative contrast-enhanced CT between January 2020 and December 2021. Occult PMs means PMs that are missed by CT but later diagnosed by laparoscopy or laparotomy. Patients with NPM means patients have neither PM nor other distant metastases, indicating there is no evidence of distant metastases in patients with AGC. Patients' clinical characteristics and CT features such as tumor marker, Borrmann IV, enhancement patterns, and pelvic ascites were observed by 2 experienced radiologists. Computed tomography features and clinical characteristics were combined to construct an indicator for identifying the presence of OPM in patients with AGC based on a logistic regression model. Receiver operating characteristic curves and the area under the receiver operating characteristic curve (AUC) were generated to assess the diagnostic performance of the combined indicator. RESULTS: Four independent predictors (Borrmann IV, pelvic ascites, carbohydrate antigen 125, and normalized arterial CT value) differed significantly between OPM and NPM and performed outstandingly in distinguishing patients with OPM from those without PM (AUC = 0.643-0.696). The combined indicator showed a higher AUC value than the independent risk factors (0.820 vs 0.643-0.696). CONCLUSIONS: The combined indicator based on abdominopelvic CT features and carbohydrate antigen 125 may assist clinicians in identifying the presence of CT OPMs in patients with AGC.

Comparison of opioid-free and opioid-inclusive propofol anaesthesia for thyroid and parathyroid surgery: a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures. METHODS: We conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery. RESULTS: We assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p < 0.001), yielding a number needed to treat of 5.3. Additionally, opioid-free propofol anaesthesia was associated with a reduced need for rescue anti-emetics, lower rates of hypotension and desaturation after tracheal extubation, and higher patient satisfaction. Time to tracheal extubation was prolonged slightly in the opioid-free group. The two groups had similar postoperative pain scores and 30-day outcomes. DISCUSSION: Opioid-free propofol anaesthesia reduced postoperative nausea and vomiting in patients undergoing thyroid and parathyroid surgery. An opioid-free anaesthetic regimen can optimise anaesthetic care during thyroid and parathyroid surgery.

Pollution and source-specific risk analysis of potentially toxic metals in urban soils of an oasis-tourist city in northwest China.

Source-specific risk apportionment for soil potentially toxic metals (PTMs) is of great significance for contamination prevention and risk management in urban environments. Eighty-five urban soil samples were obtained from an oasis-tourist city, China and examined for eight PTMs (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn). The pollution levels, sources, and ecological risk of soil PTMs were quantified, and their source-specific ecological and human health effects were also estimated using the multi-proxy approaches. The results demonstrated that accumulation of Cd, Hg, Pb, Cr, Cu, and Zn in soils was observed compared to their background levels, and the soils experienced varying degrees of PTMs pollution, especially at sites with high-intensity anthropogenic activities. Natural sources, atmospheric deposition, industrial sources, vehicular emissions, and comprehensive inputs were the principal sources, with contributions of 29.28%, 25.86%, 20.13%, 16.50%, and 8.23%, respectively. The integrated ecological risks of PTMs in soils were moderate at most sites, with atmospheric deposition being the dominant contributor to ecological risks. Children exhibited pronounced non-cancer risks, but adults had no notable non-cancer risks. Moreover, there were potential carcinogenic risks for both children and adults within the study region. Non-cancer and carcinogenic risks were more significant for children than adults, and traffic emissions were the primary contributor to non-cancer risks (adults: 20.53%, children: 20.49%) and carcinogenic risks (adults: 22.95%, children: 22.08%). The industrial and traffic activities were considered as priority control sources for soil pollution control and risk management, with Hg, Cd, Zn, and Pb corresponding to the priority elements. This study highlights the source-specific ecological and human health effects of PTMs pollution in urban soils, thereby providing valuable information for targeted pollution control and priority source management.

Enantioselective Construction of C-SCF3 Stereocenters via Nickel Catalyzed Asymmetric Negishi Coupling Reaction.

The construction of the SCF3-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF3-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC2F5, SC3F7, SC4F9, SCF2CO2Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF3-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.

Single-nucleus Atlas of Sevoflurane-induced Hippocampal Cell Type- and Sex-specific Effects during Development in Mice.

BACKGROUND: Multiple neonatal exposures to sevoflurane induce neurocognitive dysfunctions in rodents. The lack of cell type-specific information after sevoflurane exposure limits the mechanistic understanding of these effects. In this study, the authors tested the hypothesis that sevoflurane exposures alter the atlas of hippocampal cell clusters and have neuronal and nonneuronal cell type-specific effects in mice of both sexes. METHODS: Neonatal mice were exposed to 3% sevoflurane for 2 h at postnatal days 6, 8, and 10 and analyzed for the exposure effects at postnatal day 37. Single-nucleus RNA sequencing was performed in the hippocampus followed by in situ hybridization to validate the results of RNA sequencing. The Morris Water Maze test was performed to test neurocognitive function. RESULTS: The authors found sex-specific distribution of hippocampal cell types in control mice alongside cell type- and sex-specific effects of sevoflurane exposure on distinct hippocampal cell populations. There were important changes in male but not in female mice after sevoflurane exposure regarding the proportions of cornu ammonis 1 neurons (control vs. sevoflurane, males: 79.9% vs. 32.3%; females: 27.3% vs. 24.3%), dentate gyrus (males: 4.2% vs. 23.4%; females: 36.2% vs. 35.8%), and oligodendrocytes (males: 0.6% vs. 6.9%; females: 5.9% vs. 7.8%). In male but not in female mice, sevoflurane altered the number of significantly enriched ligand-receptor pairs in the cornu ammonis 1, cornu ammonis 3, and dente gyrus trisynaptic circuit (control vs. sevoflurane, cornu ammonis 1-cornu ammonis 3: 18 vs. 42 in males and 15 vs. 21 in females; cornu ammonis 1-dentate gyrus: 21 vs. 35 in males and 12 vs. 20 in females; cornu ammonis 3-dentate gyrus: 25 vs. 45 in males and 17 vs. 20 in females), interfered with dentate gyrus granule cell neurogenesis, hampered microglia differentiation, and decreased cornu ammonis 1 pyramidal cell diversity. Oligodendrocyte differentiation was specifically altered in females with increased expressions of Mbp and Mag. In situ hybridization validated the increased expression of common differentially expressed genes. CONCLUSIONS: This single-nucleus RNA sequencing study reveals the hippocampal atlas of mice, providing a comprehensive resource for the neuronal and nonneuronal cell type- and sex-specific effects of sevoflurane during development.

Comparing intracorporeal mechanical anastomosis vs. hand-sewn esophagojejunostomy after total laparoscopic gastrectomy for esophagogastric junction cancer: a single-center study.

OBJECTIVE: This study aimed to compare the effects of continuous hand-sewn esophagojejunostomy with barbed suture and mechanical anastomosis in total laparoscopic gastrectomy for esophagogastric junction cancer. MATERIALS AND METHODS: The clinical data of 60 patients who underwent total laparoscopic total gastrectomy from January 2020 to October 2021 were collected retrospectively. Baseline data and short-term surgical results of patients in the hand-sewn anastomosis (n = 30) and mechanical anastomosis (n = 30) groups were analyzed. RESULTS: No significant differences were detected in the baseline data between groups. Meanwhile, the hand-sewn group had a shorter anastomosis time (21.2 ± 4.9 min vs. 27.9 ± 6.9 min, p < 0.001) and a decreased operation cost (CNY 70608.3 ± 8106.7 vs. CNY 76485.6 ± 3149.9, p = 0.001). The tumor margin distance in the hand-sewn group was longer than in the mechanical group (2.7 ± 0.4 cm vs. 2.2 ± 0.75 cm, p = 0.002). In esophagojejunostomy anastomosis, the distance between the jejunal opening and jejunal stump in the hand-sewn group was significantly shorter than that in the mechanical group (2.2 ± 0.54 cm vs. 5.7 ± 0.6 cm, p < 0.001). No significant difference was detected in the incidence of postoperative anastomotic complications. CONCLUSION: The continuous hand-sewn anastomosis with barbed suture in total laparoscopic gastrectomy for esophagogastric junction cancer is practical, safe, and cost-effective. It is also an effective supplementary technique for mechanical anastomosis.

Contamination, ecological-health risks, and sources of potentially toxic elements in road-dust sediments and soils of the largest urban riverfront scenic park in China.

Identifying the contamination and sources of potentially toxic elements (PTEs) in road-dust sediment (RDS) and the surrounding greenspace soil of urban environments and understanding their ecological-health risks are important for pollution management and public health. The contamination characteristics, ecological and probabilistic health risks, and source apportionment of eight PTEs (Cd, Pb, Cr, Cu, Ni, As, Zn, and Hg) in the Yellow River Custom Tourist Line of Lanzhou, which is the largest open urban riverfront scenic park in China, were investigated. The results showed that all the RDS PTE mean concentrations exceeded their soil background values, whereas for the surrounding greenspace soils, the concentrations of the PTEs, except for Cr and Ni, were also higher than their local background levels. Moreover, the RDS-soil system was mainly contaminated by Cd, Zn, Pb, Cu, and Hg to varying degrees, and the integrated ecological risks of PTEs in the RDS and soil were high and considerable at most sites, respectively. The probabilistic health risk assessment results demonstrated that the non-carcinogenic hazard risk for humans was negligible, but the total carcinogenic risks should be considered. Source apportionment using a positive matrix factorization model combined with multivariate statistical analyses revealed that Cr, Ni, and As in the RDS-soil system were from natural and industrial sources, Cd, Pb, Zn, Cu came from vehicle emissions and pesticide and fertilizer applications, and Hg was from natural and industrial sources and utilization of pesticides with fertilizers. This work provides scientific evidence for urban planning and human health protection in urban environments.

Enantioselective Synthesis of Secondary ß-Trifluoromethyl Alcohols via Catalytic Asymmetric Reductive Trifluoroalkylation and Diastereoselective Reduction.

Fluorinated motifs are frequently encountered in drugs and agrochemicals. Incorporating fluorine-containing motifs in drug candidates for lead optimization in pharmaceutical research and development has emerged as a powerful tool. The construction of molecules that feature a trifluoromethyl (CF3-) group on a stereogenic carbon has accumulated broad research efforts. Unlike its well-explored, biologically active methyl counterpart, asymmetric construction of ß-trifluoromethylated alcohols bearing adjacent stereocenters still remains elusive. Through retrosynthetic analysis, we posited that followed by sequential reduction of carbonyl, the initial construction of chiral α-trifluoromethylated ketones could render the desired product in a facile, one-pot fashion. Herein, we developed the first example of nickel-catalyzed asymmtric reductive cross-coupling trifluoroalkylation of acyl chlorides for enantioselective synthesis of diverse α-trifluoromethylated ketones. The one-pot reduction of these α-trifluoromethylated ketones furnished corresponding alcohols bearing ß-CF3-substituted stereogenic carbons with excellent diastereoselectivity and complete enantioselective retention. High yields/enantioselectivity, mild conditions, and good functional group compatibility are shown in the system. Utilities of the method are also illustrated by applying asymmetric, late-stage trifluoroalkylation of biologically active complex molecules, revealing tremendous potential for development of CF3-containing chiral drugs.

Modular Difunctionalization of Unactivated Alkenes through Bio-Inspired Radical Ligand Transfer Catalysis.

Development of visible light-mediated atom transfer radical addition of haloalkanes onto unsaturated hydrocarbons has seen rapid growth in recent years. However, due to its radical chain propagation mechanism, diverse functionality other than the pre-existing (pseudo-)halide on the alkyl halide source cannot be incorporated into target molecules in a one-step, economic fashion. Inspired by the prominent reactivities shown by cytochrome P450 hydroxylase and non-heme iron-dependent oxygenases, we herein report the first modular, dual catalytic difunctionalization of unactivated alkenes via manganese-catalyzed radical ligand transfer (RLT). This RLT elementary step involves a coordinated nucleophile rebounding to a carbon-centered radical to form a new C-X bond in analogy to the radical rebound step in metalloenzymes. The protocol leverages the synergetic cooperation of both a photocatalyst and earth-abundant manganese complex to deliver two radical species in succession to minimally functionalized alkenes, enabling modular diversification of the radical intermediate by a high-valent manganese species capable of delivering various external nucleophiles. A broad scope (97 examples, including drugs/natural product motifs), mild conditions, and excellent chemoselectivity were shown for a variety of substrates and fluoroalkyl fragments. Mechanistic and kinetics studies provide insights into the radical nature of the dual catalytic transformation and support radical ligand transfer (RLT) as a new strategy to deliver diverse functionality selectively to carbon-centered radicals.

An Optimally Designed Engineering Exosome-Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing.

Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno-engineered exosome (PCOF@E-Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E-Exo is collected from TNF-α-treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti-inflammatory M2 macrophage polarization, but also stabilizes hypoxia-inducible factor-1α (HIF-1α). More importantly, the PCOF@E-Exo exhibits intriguing bactericide capabilities toward Gram-negative, Gram-positive, and drug-resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.

Remote Ischemic Preconditioning Reduces Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

Comparison of Computed Tomography Features of Gastric and Small Bowel Gastrointestinal Stromal Tumors With Different Risk Grades.

OBJECTIVE: This study aimed to compare the computed tomography (CT) features of gastric and small bowel gastrointestinal stromal tumors (GISTs) and further identify the predictors for risk stratification of them, respectively. METHODS: According to the modified National Institutes of Health criteria, patients were classified into low-malignant potential group and high-malignant potential group. Two experienced radiologists reviewed the CT features including the difference of CT values between arterial phase and portal venous phase (PVPMAP) by consensus. The CT features of gastric and small bowel GISTs were compared, and the association of CT features with risk grades was analyzed, respectively. Determinant CT features were used to construct corresponding models. RESULTS: Univariate analysis showed that small bowel GISTs tended to present with irregular contour, mixed growth pattern, ill-defined margin, severe necrosis, ulceration, tumor vessels, heterogeneous enhancement, larger size, and marked enhancement compared with gastric GISTs. According to multivariate analysis, tumor size (P < 0.001; odds ratio [OR], 3.279), necrosis (P = 0.008; OR, 2.104) and PVPMAP (P = 0.045; OR, 0.958) were the independent influencing factors for risk stratification of gastric GISTs. In terms of small bowel GISTs, the independent predictors were tumor size (P < 0.001; OR, 3.797) and ulceration (P = 0.031; OR, 4.027). Receiver operating characteristic curve indicated that the CT models for risk stratification of gastric and small bowel GISTs both achieved the best predictive performance. CONCLUSIONS: Computed tomography features of gastric and small bowel GISTs are different. Furthermore, the qualitative and quantitative CT features of GISTs may be favorable for preoperative risk stratification.

Prognostic value of circulating tumor cells and its association with the expression of cancer stem cells in nasopharyngeal carcinoma patients.

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.

Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol.

BACKGROUND: Osteoarthritis (OA) is a major cause of pain and disability worldwide. Despite the relatively high burden of the disease, the currently available non-surgical treatment options are directed towards symptomatic relief. Therefore, we propose the use of alendronate as a disease modifying agent to help slow and prevent OA. In addition, this study will utilize Whole-Organ Magnetic Resonance Imaging Score (WORMS) to evaluate the structural integrity of cartilage in the study population. High-quality evidence, limited to a few well-conducted randomized trials, highlights contradictory results on the effect of bisphosphonates on knee function and progression of OA. Therefore, a placebo-controlled, randomized trial is needed to evaluate the combined effect of alendronate and vit D on the structure of cartilage utilizing the WORMS score and its ability to treat knee pain in OA patients. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study will evaluate the efficacy and safety of alendronate in early OA. Patients will undergo a 1:1 double-blinded randomization to receive a one-year course of either alendronate sodium vitamin D3 or placebo. The primary outcome is to compare WORMS score of knee joint at 6 and 12 months between both groups. Secondary endpoints will include WORMS score at 24 months, knee pain, radiographic progression of OA, severity of OA, quality of life, and serum inflammatory biomarkers at different assessment timepoints. To detect a 2.2% difference in cartilage loss between both groups with power of 80%, a sample size of 60 (30 per group) is proposed. DISCUSSION: This trial will give helpful and high-quality evidence regarding the potential therapeutic role of alendronate sodium vitamin D3, as compared to placebo, in the management of patients with knee OA regarding its role on cartilage loss, radiographic progression of OA, severity of OA, knee pain, quality of life, and inflammatory biomarkers. If proven effective, this intervention would be a great option for providing beneficial outcomes with a reduced cost in this patient population. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (registration number: NCT04739592 ).

Possible Risk Factors for Severe Complications Occurring after Primary Total Knee Arthroplasty.

Objective Total knee arthroplasty is one of the most common orthopedic surgeries. Readmission due to severe complications after total knee arthroplasty is a grave concern to surgeons. In this study, we evaluated the risk factors for severe complications after primary total knee arthroplasty. Methods We retrospectively collected clinical data of 2,974 patients who underwent primary total knee arthroplasty from July 2013 to June 2019 in our hospital. Postoperative complication ≥ grade Ⅲ was defined as severe complication according to Clavien-Dindo classification system. Binary logistic regression was used to identify the predictive risk factors for severe complications. Results The complication rate after primary total knee arthroplasty was 6.8% and severe complication rate was 2.5%. Male (OR = 2.178, 95%CI: 1.324-3.585, P= 0.002), individuals above 75 years old (OR = 1.936, 95%CI: 1.155-3.244, P= 0.012), arrhythmia (OR = 2.913, 95%CI: 1.350-6.285, P= 0.006) and cerebrovascular disease (OR = 2.804, 95%CI: 1.432-5.489, P= 0.003) were predictive risk factors for severe complications after primary total knee arthroplasty. Conclusion Advanced age, male, arrhythmia, and cerebrovascular disease might be patients-related risk factors for postoperative severe complications after primary total knee arthroplasty. Special attention should be paid to patients with risk factors.

[Clinical Characteristics of 68 Patients with Osteoarticular Tuberculosis].

Objective To analyze the clinical features of patients with osteoarticular tuberculosis. Method This retrospective study included a cohort of 68 osteoarticular tuberculosis patients hospitalized in Peking Union Medical College Hospital from January 2013 to December 2020.Results The patients included 42(61.8%)males and 26(38.2%)females,with a median age of 56 years.Tuberculosis pathogen was detected in 39(57.4%)patients,and 29(42.6%)patients were diagnosed by clinical manifestations.The median time from onset to diagnosis was 4 months.The most common manifestations were pain and dysfunction(86.8%),followed by fever(47.1%),weight loss(36.8%),and night sweats(13.2%).Concomitant active tuberculosis in other organs was observed in 27(39.7%)patients.Unifocal and multifocal osteoarticular tuberculosis occurred in 51(75.0%)patients and 17(25.0%)patients,respectively,which mainly attacked thoracic and lumbar spines.Tuberculosis T cell test was positive in 92.7% patients.All the bone biopsies revealed epithelioid granuloma with/without necrosis,with 75.0% positive for mycobacterial DNA,55.1% positive for mycobacterial culture,and 20% positive for acid-fast staining.The risk of developing multifocal osteoarticular tuberculosis in the patients with weight loss was 5.333 times(P=0.013)that of the patients with stable weight.Conclusions The diagnosis of osteoarticular tuberculosis is difficult and tuberculosis T cell test is an effective means.Bone biopsy is the key to diagnosis,and the PCR of mycobacterial DNA shows the highest positive derection rate.Multifocal osteoarticular tuberculosis is not rare,especially in the patients with weight loss.Thus,a comprehensive imaging evaluation is recommended to avoid missed diagnosis.