Objective To investigate the development, role, and regulatory mechanism of macrophage efferocytosis in the liver of hosts infected with Schistosoma japonicum. Methods The expression of efferocytosis-related gene like efferocytosis receptors, efferocytosis-related bridging molecules,“eat me” signal and “don’t eat me” signal was detected in the livers of patients and mice infected with S. japonicum in the Gene Expression Omnibus (GEO) database. Ten wild-type (WT) male mice (6 ~ 8 weeks old, weighing 20 ~ 25 g) were randomly divided into a Schistosoma japonicum infection (SJ) group and a normal control (NC) group, with 5 mice in each group. The efferocytosis of neutrophils and T cells by liver macrophages was detected in mice from SJ group and NC group using flow cytometry and immunofluorescence assay, respectively. The expression of efferocytosis-related Mer receptor tyrosine kinase (MerTK) and Axl receptor tyrosine kinase (Axl) proteins was determined in mouse liver tissues using Western blotting assay, and the proportion of MerTK⁺ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers using flow cytometry. Changes in liver granulomas and fibrosis were observed in mice infected with S. japonicum following injection of efferocytosis inhibitors, and S. japonicum-infected mice without injection of efferocytosis inhibitors served as controls. Bone marrow-derived macrophages (BMDMs) were isolated from macrophage scavenger receptor class A (SR-A) conditional knockout (CKO) and wild-type (WT) mice, and changes in apoptotic neutrophils were detected in SR-A CKO mouse macrophages in vitro using flow cytometry. Then, BMDMs was divided into the WT mono-culture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group, and the expression of MerTK and Axl was quantified in vitro using Western blotting and real-time quantitative PCR (RT-qPCR) assays during neutrophil efferocytosis. The efferocytosis of neutrophils and T cells by mouse liver macrophages was detected in the SR-A CKO SJ group and the WT SJ group using flow cytometry and immunofluorescence assay, and the expression of MerTK and Axl proteins was determined in mouse liver tissues in both groups using Western blotting. In addition, the proportion of MerTK⁺ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers in both groups using flow cytometry. Results Data from the GEO database showed that the expression of some efferocytosis receptors and efferocytosis-related bridging molecules, and “eat me” and “don’t eat me” signals all appeared a tendency towards a rise in livers of patients and mice in the SJ group relative to the NC group, suggesting that S. japonicum infection-induced liver diseases may be associated with efferocytosis. Flow cytometry detected higher proportions of Ly6G⁺ cells [(13.13 ± 0.45)% vs. (6.48 ± 0.25)%; t = 22.30, P < 0.05] and CD3⁺ cells [(7.60 ± 0.33)% vs. (3.30 ± 0.42)%; t = 13.98, P < 0.05] in mouse liver macrophages in the SJ group than in the NJ group, and the expression of MerTK protein [(2.30 ± 0.14) vs. (1.14 ± 0.46); t = 4.19, P < 0.05], the mean fluorescence intensity of macrophages [(160.67 ± 15.28) vs. (94.50 ± 19.61); t = 4.81, P < 0.05], and the proportion of MerTK⁺ macrophages [(20.78 ± 4.17)% vs. (6.85 ± 0.39)%; t = 6.57, P < 0.05] were significantly higher in mouse liver tissues in the SJ group than in the NC group. The Axl expression was lower in mouse liver tissues in the SJ group than in the NC group [(1.25 ± 0.08) vs. (1.93 ± 0.37); t = 2.79, P < 0.05], and the area of granulomas around single eggs [(9.18 ± 1.81) × 10⁴μm² vs. (5.24 ± 1.35) × 10⁴ μm²; t = 3.03, P < 0.05] and proportion of collagen fibers [(25.27 ± 3.99)% vs. (15.14 ± 4.02)%; t = 3.10, P < 0.05] were significantly greater in livers of S. japonicum-infected mice with injection of efferocytosis inhibitors than in mice without injection of efferocytosis inhibitors. The in vitro efferocytosis efficiency of BMDMs [(32.83 ± 3.17)% vs. (45.43 ± 2.34)%; t = 5.54, P < 0.05], and the proportions of Ly6G⁺ [(9.37 ± 0.48)% vs. (13.13 ± 0.72)%; t = 7.50, P < 0.05] and CD3⁺ cells [(4.95 ± 0.17)% vs. (7.64 ± 0.50)%; t = 8.87, P < 0.05] in liver macrophages post-infection with S. japonicum were significantly lower in SR-A CKO mice than in WT mice, and the expression of MerTK protein [(0.65 ± 0.25) vs. (1.96 ± 0.69); t = 3.10, P < 0.05], the average fluorescence intensity of macrophages [(138.33 ± 8.39) vs. (160.67 ± 15.28); t = 3.03, P < 0.05] and the proportion of MerTK⁺ macrophages [(13.17 ± 5.01)% vs. (22.63 ± 2.06)%; t = 3.56, P < 0.05] were significantly lower in mouse liver tissues in the SR-A CKO SJ group than in the WT group. Western blotting detected no significant difference in the Axl protein expression in mouse liver tissues between the SR-A CKO SJ group and the WT SJ group [(0.48 ± 0.07) vs. (0.68 ± 0.30); t = 1.09, P > 0.05]. There were significant differences in the relative MerTK mRNA and protein expression during efferocytosis of BMDMs among the WT monoculture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group (F = 9.41 and 40.68, both P values < 0.05). In addition, there was a significant difference in the relative Axl mRNA expression during efferocytosis of BMDMs among the four groups (F = 13.62, P < 0.05); however, no significant difference was seen in the relative Axl protein expression (F = 1.27, P > 0.05). Conclusions Efferocytosis of liver macrophages is seen in mice infected with S. japonicum and inhibits liver fibrosis. SR-A may up-regulate the efficiency of macrophage efferocytosis through regulating the expression of efferocytosis receptors.

Commonly used anesthetic sedatives(opioids,benzodiazepines,ketamine,propofol,etc.)share the risk of inducing respiratory depression,and their multi-target mechanism of action pres-ents significant heterogeneity.Opioids inhibit the rhythmic activity of the respiratory center of the medulla bulbar(such as the PreB?tzinger complex and parbrachial nucleus)by activating both the μ-opioid receptor and the G-protein-gated inwardly-rectifying potassium channel and β-arrestin signaling pathway,resulting in decreased respiratory frequency and amplitude.Benzodiazepines enhance inhibitory neurotransmis-sion mediated by γ-aminobutyric acid receptors,reduce the sensitivity of chemoreceptors to PaCO2 and PaO2,and lead to a decreased tidal volume and upper airway obstruction.Ketamine inhibits respiratory drive and respiratory muscle function by blocking N-methyl-D-aspartic acid receptors and indirectly affecting the μ-opioid receptor.In addition,propofol inhibits pre-expiratory neuronal activity and relaxes upper airway muscles by activating the GABAA receptor β3 subunit.Currently,specific antagonists(naloxone/flumazenil)and respiratory stimulants(doxapram)are clinically used to treat respiratory depression,but they have defects such as short duration of action and insufficient specificity.The devel-opment of novel stimulants targeting μ-opioid receptor agonists and the D-serine release pathway of astrocytes,as well as broad-spectrum antidotes based on"molecular cage"technology,has become a new sphere of research that aims at precisely reversing respiratory depression while preserving analgesic and sedative effects.This article reviews the biological mechanisms of respiratory depression caused by sedative hypnotic anesthetic drugs,explores the advantages and disadvantages of treatments currently availabe,and proposes new strategies for improving respiratory depression in the future.

Commonly used anesthetic sedatives(opioids,benzodiazepines,ketamine,propofol,etc.)share the risk of inducing respiratory depression,and their multi-target mechanism of action pres-ents significant heterogeneity.Opioids inhibit the rhythmic activity of the respiratory center of the medulla bulbar(such as the PreB?tzinger complex and parbrachial nucleus)by activating both the μ-opioid receptor and the G-protein-gated inwardly-rectifying potassium channel and β-arrestin signaling pathway,resulting in decreased respiratory frequency and amplitude.Benzodiazepines enhance inhibitory neurotransmis-sion mediated by γ-aminobutyric acid receptors,reduce the sensitivity of chemoreceptors to PaCO2 and PaO2,and lead to a decreased tidal volume and upper airway obstruction.Ketamine inhibits respiratory drive and respiratory muscle function by blocking N-methyl-D-aspartic acid receptors and indirectly affecting the μ-opioid receptor.In addition,propofol inhibits pre-expiratory neuronal activity and relaxes upper airway muscles by activating the GABAA receptor β3 subunit.Currently,specific antagonists(naloxone/flumazenil)and respiratory stimulants(doxapram)are clinically used to treat respiratory depression,but they have defects such as short duration of action and insufficient specificity.The devel-opment of novel stimulants targeting μ-opioid receptor agonists and the D-serine release pathway of astrocytes,as well as broad-spectrum antidotes based on"molecular cage"technology,has become a new sphere of research that aims at precisely reversing respiratory depression while preserving analgesic and sedative effects.This article reviews the biological mechanisms of respiratory depression caused by sedative hypnotic anesthetic drugs,explores the advantages and disadvantages of treatments currently availabe,and proposes new strategies for improving respiratory depression in the future.

Objective:To investigate the clinical value of neuroendoscopic resection in recurrent or residual sellar and clivus tumors and the prevention and treatment of operative complications.Methods:A retrospective study was performed. Clinical data of 49 patients with residual or recurrent sellar and clivus tumors after neuroendoscopic resection in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from November 2021 to October 2023 were collected; 45 patients were with pituitary adenoma, 3 were with craniopharyngioma, and 1 patient was with clivus chordoma; their surgical efficacy and complications were summarized and analyzed.Results:Total resection was achieved in 29 patients (59.2%), subtotal resection in 12 (24.5%), and partial resection in 8 (16.3%). Two patients (4.1%) had intraoperative internal carotid artery rupture and were given emergency laminar stenting, discharging with good recovery, but one of them left with unilateral motor nerve palsy. During 1-24 months of follow-up, 97.2% patients (35/36) had headache relief and visual acuity improvement, and no patient had permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. Residual tumors increased in 3 patients (6.1%); no tumor recurrence after total resection was noted.Conclusion:Endoscopic resection of recurrent or residual sellar and clivus tumors is safe and effective; attention should be paid to the internal carotid artery during the operation.

Objective This study prepared gelatin three-dimensional porous microspheres and investigated the feasibility of gelatin three-dimensional porous microspheres loaded with quercetin(G-quercetin)as bone tissue scaffold material.Methods Porous gelatin microspheres were prepared by emulsification and loaded with quercetin by lyophilization.Scanning electron microscopy was used to ob-serve morphology of the microspheres.The cytotoxicity of G-quercetin microspheres and their effects on the adhesion,proliferation and differentiation of mouse embryonic osteoblast precursor cells(MC3T3-E1)were detected by immunofluorescence staining,live/dead cell staining and CCK-8 assay,alkaline phosphatase(ALP)staining and alizarin red staining.RT-PCR was used to detect the tran-scriptional levels of osteoblast-related cytokines such as Runx-2,ALP,OPN and OCN.Results The scanning electron microscopy re-sults showed that the prepared three-dimensional microporous material loaded with quercetin gelatin had a porous structure.Cell adhe-sion showed that the cells could spread well on the surface of the microspheres.Compared with the control group,the results of live/dead cell staining and CCK-8 detection showed that the microspheres had no significant cytotoxicity(P＞0.05).Compared with the con-trol group,G-quercetin microspheres showed an increase in ALP expression and mineralization in vitro.PCR results also showed a sig-nificant increase in Runx-2,ALP,OCN,OPN(P＜0.05).Conclusion The G-quercetin porous microspheres prepared in this experi-ment have good biocompatibility and can promote the osteogenic differentiation of MC3T3-E1 in vitro.It is expected to be used as a new scaffold material for bone tissue engineering.

Objective:To investigate the effect of treatment of spinal meningioma with microsurgical procedures.Methods:From January 2003 to March 2022, there were 120 patients who had spinal meningioma and treated in the Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University. Their clinical data were retrospectively analysed. Of the 120 patients, there were 90 females and 30 males, aged from 14 to 85 (average, 54) years old. According to McCormick Classification, 29 cases were in grade I, 59 cases were in grade II, 25 cases were in grade III, and 7 cases were in grade IV. They were all underwent microsurgery. Patients were followed up by outpatient service within 3 months after surgery, then reviewed by outpatient visits and telephone interviews. McCormick's classification method and MRI examination were used to analyse the neurological and imaging changes of the patients before and after the surgery.Results:A total of 113 patients had complete resection and 7 had the resection of most part of the spinal meningioma. No infection, cerebrospinal fluid leakage, other complications and death occurred. Three months after surgery, 95 patients achieved the improvement or even completely disappearance of symptoms (such as numbness, pain, limited movement, etc.). There were 23 patients who had the symptoms unchanged as what before the surgery. Two patients had the symptoms worsened after the surgery. At 3 months after surgery, 95 cases (79.2%) improved, 23 cases (19.2%) were stable, and 2 cases (1.6%) aggravated. According to McCormick classification method, 92 cases were in grade Ⅰ, 15 cases were in gradeⅡ, 10 cases were in grade Ⅲ, and 3 cases were in grade Ⅳ. MRI scans showed that the dural sac were well refluxed, and no recurrence was found.Conclusion:Microsurgery is safe and effective for removal of spinal meningioma, with significant improvement in symptoms with fewer complications.

Objective:To investigate the clinical efficacy of microsurgical resection in primary jugular foramen schwannomas (JFSs).Methods:A retrospective analysis was performed; the clinical data of 58 patients with JFSs treated by microsurgery in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from May 2012 to June 2021 were collected. Seven patients accepted microsurgery via suboccipital retrosigmoid approach, and 51 patients accepted microsurgery via jugular foramen approach. Fifty-three patients were followed up for 4.5 years (ranged from 0.5-8.5 years); follow-ups included Karnofsky performance status (KPS) scores, postoperative complications, and imaging reexaminations. Results:Fifty patients (86.2%) achieved total tumor resection and 8 (13.8%) subtotal resection. The KPS scores at discharge were 68.6±14.9, which were significantly lower than the preoperative KPS scores (77.6±13.5, t=2.452, P=0.017). During the follow-up, 5 patients(9.4%) had tumor recurrence, and 39 patients (73.6%) had improved symptoms after surgery. One patient (1.9%, modified Samii D type) died of cerebellar hemorrhage and swelling after surgery. The main complications included new/aggravated hoarseness (11/53), cerebrospinal fluid leakage (7/53), new/aggravated dysphagia (5/53), and new facial paralysis (4/53). Conclusion:In microsurgical resection of JFSs, short-term symptoms of the lower cranial nerves may be exacerbated, but long-term results are good.

Objective:To explore the clinical effect of the fractional carbon dioxide laser in the treatment of contracture scars.Methods:A retrospective before-after self-control study was conducted. From December 2016 to April 2021, 16 patients (7 males and 9 females, aged 3-49 years) with contracture scars causing impaired function of the adjacent joint were admitted to Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Eighteen joint scars of 16 patients were treated with fractional carbon dioxide laser every 2-3 months until the joint retained its normal range of motion or the effect plateaued. The treatment times of each patient were recorded. Before the first treatment and 6 months after the last treatment, the ranges of motion of the affected joint were measured in each patient, and the difference was calculated, meanwhile, the Vancouver Scar Scale (VSS) was used to evaluate the scar of each patient. In the treatment of 1 joint scar in each of 6 patients (totally 6 times of treatments), the ranges of motion of the affected joint before the current treatment, immediately after the treatment, and at the first follow-up after the treatment were documented, and the differences between the ranges before and immediately after the treatment as well as between the ranges before and at the first follow-up after the treatment were calculated. Adverse effects after the treatment in the treatment area were documented. At the last follow-up, a self-made questionnaire was used to collect the implementation status of the physical therapy and other scar management modalities during the treatment interval and follow-up period. Data were statistically analyzed with Wilcoxon rank sum test.Results:Eighteen joint scars in 16 patients received 2 (1, 3) times of fractional carbon dioxide laser treatment. The range of motion of the affected joint of 16 patients 6 months after the last treatment was 56.5 (39.0, 128.8)°, notably higher than 38.4 (22.9, 116.3)° before the first treatment ( Z=-3.724, P<0.01), showing a remarkable improvement by 17.4 (8.0, 24.1)°. The vascular distribution, softness, and thickness scores, and total score in VSS scoring of scars of 16 patients 6 months after the last treatment were significantly lower than those before the first treatment ( Z=-2.989, -3.762, -2.814, -3.739, P<0.01), with the most obvious improvement in softness. In 6 times of treatments, the range of motion of the affected joint immediately after treatment and at the first follow-up of (2.5±0.6) months after treatment were 156.2 (148.0, 164.2)° and 160.2 (156.7, 166.4)°, both notably higher than 151.4 (145.7, 155.3)° before treatment ( Z=-2.201, -2.201, P<0.05), showing a remarkable improvement by 9.1 (4.4, 13.0)° and 13.1 (8.0, 15.7)°, respectively. No adverse effects such as blisters, infection, or hypertrophic scar formation were observed in the treatment area of 16 patients after treatment. Most patients adopted physical therapy, compression, silicone gel or sheets, and braces during the treatment interval and follow-up period. Conclusions:The fractional carbon dioxide laser can soften the scar and increase the range of motion of the affected joint, which is suitable for the clinical treatment of mild contracture scars.

A case of Gilbert syndrome (GS) with a heterozygous mutation in the gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. *28 and c.211G>A heterozygous mutations in gene were found, which may be another type of mutation causing GS in Chinese population.
Asian Continental Ancestry Group ; Bilirubin ; Gilbert Disease ; genetics ; Glucuronosyltransferase ; genetics ; Heterozygote ; Humans ; Mutation

Objective:To investigate the value of pericoronary adipose tissue histogram parameters based on coronary CT angiography (CTA) images for the differentiation of acute coronary syndrome and stable coronary artery disease.Methods:The clinical data and CTA images of 93 patients with coronary CTA examination in Suzhou Kowloon Hospital from 2013 to 2018 were analyzed retrospectively. There were 39 patients with acute coronary syndrome (acute coronary syndrome group) and 54 patients with stable coronary artery disease (stable coronary artery disease group). A region of interest (ROI) was drawn around the stenosis of the coronary arteries, with CT attenuation ranging from-190 to -30 HU to exclude non-adipose tissue. The CT attenuation of ROI excluding non-adipose were measured and histogram analysis was performed. The obtained parameters included the mean value, median value and the 5th, 10th, 45th, 55th, 70th and 95th percentiles. The differences in histogram parameters between the two groups were compared, and then the value of each parameter in differentiating acute coronary syndrome and stable coronary artery disease was evaluated based on receiver operating characteristic (ROC) analysis. The stepwise regression of multivariate logistic regression analysis was used to identify the useful features and establish the final prediction model. The ROC curve of the final model was calculated and its value was analyzed.Results:The mean, median and the 5th, 10th, 45th, 55th,70th and 95th percentile differences between the acute coronary syndrome group and the stable coronary artery disease group were statistically significant (all P<0.05). The ROC curve for the median and the 95th percentile had the same area under curve (AUC) of 0.73. The sensitivity, specificity and AUC of the diagnostic model established by multiple logistic regression were 82.1%, 89.1% and 0.90 respectively. Conclusion:CT attenuation histogram of pericoronary adipose tissue is of high value in differentiating acute coronary syndrome from stable coronary artery disease.