Efficacy of multi-color near-infrared fluorescence with indocyanine green:A new imaging strategy and its early experience in laparoscopic cholecystectomy

BACKGROUND Near-infrared fluorescence imaging via using intravenous indocyanine green(ICG)has a wide range of applications in multiple surgical scenarios.In lapa-roscopic cholecystectomy(LC),it facilitates intraoperative identification of the biliary system and reduces the risk of bile duct injury.However,the usual single color fluorescence imaging(SCFI)has limitations in manifesting the fluorescence signal of the target structure when its intensity is relatively low.Moreover,sur-geons often experience visual fatigue.We hypothesized that a novel imaging stra-tegy,named multi-color fluorescence imaging(MCFI),could potentially address these issues by decreasing hepatic and background fluorescence pollution and improving biliary visualization.AIM To investigate the novel imaging strategy MCFI in LC.METHODS This was a single-center retrospective study conducted at Peking Union Medical College Hospital,Beijing,China.Patients who underwent LC from June 2022 to March 2023 by the same surgical team were enrolled.Demographic features,clinical and surgical information were collected.The clarity,visual comfort,and effectiveness of different imaging strategies were subjectively evaluated by surgeons.RESULTS A total of 155 patients were included,60 patients were in the non-ICG group in which only bright light illuminance without ICG was applied,60 patients were in the SCFI group,and 35 patients were in the MCFI group.No statist-ically significant differences were found in demographics or clinical history.Post-surgical complications were minimal in all 3 groups with no significant differences observed.MCFI improved the clarity of imaging and visual comfort.Clarity of imaging and visual comfort were improved with MCFI.CONCLUSION MCFI improves biliary visualization and reduces liver fluorescence contamination,which supports its routine use in LC.MCFI may also be a better choice than SCFI in other clinical settings.

白细胞介素-18、趋化因子配体2在血管性认知损害患者中的表达意义及诊断效能分析

目的探讨白细胞介素-18(IL-18)、趋化因子配体2(CCL2)在血管性认知损害(VCI)患者中的表达意义及对VCI的诊断效能。方法选取粤北人民医院和韶关学院医学院附属医院2019年1月—2020年4月收治的脑小血管病患者140例,根据其是否发生VCI分成VCI组(n=76)和非VCI组(n=64)。采用蒙特利尔认知评价量表(MoCA)评价两组患者的认知功能。采用酶联免疫吸附试验(ELISA)检测患者血清IL-18、CCL2水平。Pearson法分析MoCA总分与血清IL-18、CCL2的相关性。绘制受试者工作特征(ROC)曲线分析血清IL-18、CCL2对VCI的诊断效能。结果VCI组视空间与执行能力、命名、记忆、注意、语言、抽象、延迟回忆及总分低于非VCI组(P<0.05)。VCI组血清IL-18、CCL2水平高于非VCI组(P<0.05)。MoCA总分与血清IL-18水平(r=-0.828,P=0.000)、CCL2水平(r=-0.738,P=0.000)均呈负相关。血清IL-18水平诊断VCI的曲线下面积(AUC)为0.772(95%CI:0.692,0.852),敏感性为72.40%(95%CI:0.715,0.858),特异性为73.40%(95%CI:0.698,0.897);血清CCL2水平诊断VCI的AUC为0.722(95%CI:0.636,0.808),敏感性为70.30%(95%CI:0.619,0.840),特异性为74.20%(95%CI:0.644,0.868)。结论脑小血管病后VCI发生率较高,且VCI患者的血清IL-18、CCL2水平升高,两者对VCI有一定诊断价值,可作为筛查该病的重要指标。

Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury:Effects on Immune Function,Nutritional Status and Outcomes

Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN)with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patientswith severe traumatic brain injury (STBI).Methods A prospective randomized control trial was carried out from January 2009 to May 2012 inNeurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow ComaScale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were administratedEN, PN or EN＋PN treatments respectively. The indexes of nutritional status, immune function,complications and clinical outcomes were examined and compared statistically.

Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

AIM:To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy.METHODS:A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established,and the expression of PrPc,Bcl-2 and Bax was detected in these cells.Apoptosis was determined using Annexin V staining.Western blotting and immunohisto-chemistry were performed to detect the expression of PrPc in patients receiving chemotherapy and to explore the role of PrPc expression in predicting the chemosensitivity and the outcome of gastric cancer patients receiving chemotherapy.Follow-up was performed for 2 years.RESULTS:PrPc expression was increased with the increase in drug resistance.Bcl-2,together with PrPc,increased the level of anti-apoptosis of cancer cells.Increased PrPc expression predicted the enhanced level of anti-apoptosis and resistance to anticancer drugs.PrPc expression could be used as a marker for predicting the efficacy of chemotherapy and the prognosis of gastric cancer.Increased PrPc expression predicted both poor chemosensitivity and a low 2-year survival rate.Contrarily,low PrPc expression predicted favorable chemosensitivity and a relatively high 2-year survival rate.CONCLUSION:PrPc expression is associated with histological types and differentiation of gastric cancer cells;The PrPc expression level might be a valuable marker in predicting the efficacy of chemotherapy and the prognosis of gastric cancer patients receiving chemotherapy.

The Mesenchymal stem cell regulates the immune system: secretion of cytokines, cell-to-cell contact and extracellular vesicles

MSCs are pluripotent stem cells which have multipotent differentiation potential and immunosuppressive ability.Therefore,MSCs play an important role in regenerative medicine;the study of their mechanisms of regulating immune responses will also lead to new strategies for the treatment of immune-inflammatory diseases.Studies have shown that MSCs can modulate adaptive and innate immunity by secreting cytokines or cell-to-cell contact and play an immunosuppressive role.In addition,the secretion of extracellular vesicles by MSCs is also an important immunomodulatory mechanism.MSCs need to be cultured in vitro before they can be used to modulate immunity.It has been shown that pretreatment of MSCs during culture can improve cell survival rate and further enhance the ability of immunomodulation.In this paper,the mechanism of MSCs regulating immune response is discussed to deepen the understanding of MSCs regulating immunity.

The immunomodulatory effects of bone marrow-derived mesenchymal stem cells on lymphocyte in spleens of aging rats

Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.

Middle Devonian ostracods from Jiwozhai patch reef(Dushan,Guizhou Province,South China):Biostratigraphic and palaeoecological implication

The Middle Devonian ostracods from the Jiwozhai patch reef in Dushan, Guizhou Province, South China were described for the first time in this study. Twenty-nine species belonging to 20 genera were identified and figured, including a new species named Wangshangkia jiwozhaiensis sp. nov. The ostracod fauna in the Jiwozhai patch reef represents a Givetian age. The ostracod assemblage belongs to the smooth-podocopid association, which is also ecologically equivalent to the Eifelian Mega-Assemblage Ⅲ. This association is indicative of shallow open-marine environments. The Jiwozhai patch reef fauna is primarily comprised of suspension feeders, including filter-feeding ostracods, corals, brachiopods and bryozoans. Ostracods from the Jiwozhai patch reef were compared to the ostracod faunas from Laurentia-Baltica at generic level, which reveals limited faunal exchanges between South China and Laurentia-Baltica during the Middle Devonian.

Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain

The present study was designed to examine the therapeutic effects of Botulinum neurotoxin A(BoNT/A)on depression-like behaviors in mice and to explore the potential mechanisms.These results revealed that a single facial injection of BoNT/A induced a rapid and prolonged improvement of depression-like behaviors in naive and space-restriction-stressed(SRS)mice,reflected by a decreased duration of immobility in behavioral despair tests.BoNT/A significantly increased the 5-hydroxytryptamine(5-HT)levels in several brain regions,including the hippocampus and hypothalamus,in SRS mice.BoNT/A increased the expression of the N-methyl-Daspartate receptor subunits NR1 and NR2 B in the hippocampus,which were significantly decreased in SRS mice.Furthermore,BoNT/A significantly increased the expression of brain-derived neurotrophic factor(BDNF)in the hippocampus,hypothalamus,prefrontal cortex,and amygdala,which were decreased in SRS mice.Finally,BoNT/A transiently increased the levels of phosphorylated extracellular signal-regulated kinase(p-ERK)and cAMPresponse element binding protein(p-CREB),which were suppressed in the hippocampus of SRS mice.Collectively,these results demonstrated that BoNT/A treatment has antidepressant-like activity in mice,and this is associated with increased 5-HT levels and the activation of BDNF/ERK/CREB pathways in the hippocampus,supporting further investigation of BoNT/A therapy in depression.

Expressions of cardiac sympathetic norepinephrine transporter and β_1-adrenergic receptor decreased in aged rats

Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine(NE) transporter(NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the β-adrenergic receptor(β-AR). In the present study,we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2-and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA,NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%,26%,and 43%,respectively,in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.

Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

Background： Subsequent neutrophil （polymorphonuclear neutrophil [PMN]）-predominant inflammatory response is a predominant feature of ventilator-induced lung injury （VILI）, and mesenchymal stem cell （MSC） can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair inflammatory in the VILI is still unknown. This study aimed to inflammatory in the mechanical VILI. of VILI. However, whether MSC could attenuate PMN-predominant test whether MSC intervention could attenuate the PMN-predominate Methods： Sprague-Dawley rats were ventilated for 2 hours with large tidal volume （20 mL/kg）. MSCs were given before or after ventilation. The inflammatory chemokines and gas exchange were observed and compared dynamically until 4 hours after ventilation, and pulmonary pathological change and activation of PMN were observed and compared 4 hours after ventilation. Results： Mechanical ventilation （MV） caused significant lung injury reflected by increasing in PMN pulmonary sequestration, inflammatory chemokines （tumor necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein 2） in the bronchoalveolar lavage fluid, and injury score of the lung tissue. These changes were accompanied with excessive PMN activation which reflected by increases in PMN elastase activity, production of radical oxygen series. MSC intervention especially pretreatment attenuated subsequent lung injury, systemic inflammation response and PMN pulmonary sequestration and excessive PMN activation initiated by injurious ventilation. Conclusions： MV causes profound lung injury and PMN-predominate inflammatory responses. The protection effect of MSC in the VILI rat model is related to the suppression of the PMN activation.

Clinical significance of detection of antibodies to fetal and adult acetylcholine receptors in myasthenia gravis

Objective To evaluate the frequency, distribution and clinical significance of the antibodies to the fetal and/or adult acetylcholine receptor （AChR） in patients with myasthenia gravis （MG）. Methods AChR antibodies were detected by cell-based assay in the serum of ocular MG （OMG） （n = 90） and generalized MG （GMG） patients （n = 110）. The fetal-type （2α： β： γ： δ） and adult-type （2α： β： ε： δ） AChR were used as antigens, and their relevance to disease presentation was assessed. Results The overall frequencies of anti-adult and anti-fetal AChR antibodies were similar in all 200 patients examined, with 14 having serum specific to the AChR-γ subunit, and 22 to the AChR-ε subunit. The overall sensitivity when using the fetal and adult AChR antibodies was higher than that when using the fetal AChR antibody only （P = 0.015）. Compared with OMG patients, the mean age at disease onset and the positive ratio of antibodies to both isoforms of the AChR were significantly higher in patients who subsequently progressed to GMG. Older patients and patients with both anti-fetal and anti-adult AChR antibodies had a greater risk for developing generalized disease [odds ratio （OR）, 1.03; 95% confidence interval （CI）, 1.01–1.06 and OR, 5.09; 95% CI, 2.23–11.62]. Conclusion Using both fetal-and adult-type AChRs as the antigens may be more sensitive than using either subtype. Patients with serum specific to both isoforms are at a greater risk of progressing to GMG. Patients with disease onset at an advanced age appear to have a higher frequency of GMG conversion.

MicroRNA21 Meets Neuronal TLR8: Non-canonical Functions of MicroRNA in Neuropathic Pain

Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].

igh-frequency Oscillations and the Seizure Onset Zones in Neocortical Epilepsy

Background： To study the characters of high-frequency oscillations （HFOs） in the seizure onset zones （SOZ） and the nonseizure onset zones （NSOZ） in the electrocorticography （ECoG） of patients with neocortical epilepsy. Methods： Only patients with neocortical epilepsy who were seizure-free after surgery as determined with ECoG were included. We selected patients with normal magnetic resonance imaging before surgery in order to avoid the influence of HFOs by other lesions. Three minutes preictal and 1 0 rain interictal ECoG as recorded in 39 channels in the SOZ and 256 channels in the NSOZ were analyzed. Ripples and fast ripples （FRs） were analyzed by Advanced Source Analysis soltware （ASA, The Netherlands）. Average duration of HFOs was analyzed in SOZ and NSOZ separately. Results： For ripples, the permillage time occupied by HFOs was 0.83 in NSOZ and 1.17 in SOZ during the interictal period. During preictal period, they were 2.02 in NSOZ and 7.93 in SOZ. For FRs, the permillage time occupied by HFOs was 0.02 in NSOZ and 0.42 in SOZ during the interictal period. During preictal period, they were 0.03 in NSOZ and 2 in SOZ. Conclusions： High-frequency oscillations are linked to SOZ in neocortical epilepsy. Our study demonstrates the prevalent occurrence of HFOs in SOZ. More and more burst of HFOs, especially FRs, means the onset of seizures.