Discovery of natural AMPK activator from the fruits of Xanthium sibiricum Patr.: Xanthiumine A, protoberberine alkaloid with unique C28 skeleton.

Two protoberberine alkaloids with a unique C28 skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a. Their plausible biosynthetic pathway was proposed on the basis of the coexisting alkaloid monomer as the precursor. Furthermore, the effects and related molecular mechanism of compound 1 on hepatic lipid accumulation were also investigated in oleic acid (OA)-treated HepG2 cells.

Effect of oxymatrine on Cryptosporidium parvum infection in mice based on the HMGB1-TLR2/TLR4-NF-κB pathway / 中国血吸虫病防治杂志

Objective To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice. Methods Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay. Results HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05). Conclusions C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.

Effects of maximum fat oxidation intensity exercise combined with diet restriction on lipid and ferroptosis in obese college students with non alcoholic fatty liver disease / 中国学校卫生

Objective@#To compare the effects of 12week maximum fat oxidation (FATmax) intensity exercise combined with dietary restriction and FATmax intensity exercise alone on body composition, blood lipid metabolism and ferroptosis in obese college students with nonalcoholic fatty liver disease(NAFLD),so as to provide a exercise prescription reference for rehabilitation treatment of obese NAFLD college students.@*Methods@#In August 2023,a total of 45 obese NAFLD college students were divided into maximum fat oxidation intensity exercise combined with dietary restriction group (FATmax+DR, n=22) and FATmax group (n=23) by random number table method,who were recruited through online notifications and physical examinations at the Physical Examination Center of Fenyang College of Shanxi Medical University. FATmax group received FATmax intensity exercise with 3 times a week for 12 weeks (FATmax:0.51 g/min, exercise intensity:50.14% VO2max and the heart rate:136.78 times/min). FATmax+DR group underwent 12 weeks of FATmax intensity exercise combined with dietary restriction, and daily dietary energy intake was determined according to resting energy consumption. Body composition, four items of blood lipids and the indicators of oxidative stress and ferroptosis were measured before and after the intervention.The differences of indicators among each group were analyzed by using independent sample t test and paired sample t test.@*Results@#Before the intervention, there were no significant differences in body composition,four items of blood lipid, oxidative stress and iron death between FATmax+DR group and FATmax group (P>0.05). After 12 weeks of intervention, body weight , body mass index(BMI), body fat mass, trunk fat mass, visceral fat area and serum low density lipoprotein(LDL) and malondialdehyde(MDA) levels in FATmax+DR group were significantly lower than those in FATmax group, while serum high density lipoprotein(HDL) and glutathione(GSH) levels were higher than those in FATmax group (t=-2.30，-3.23,-3.97,-5.85,-3.44,-3.06,-2.03,-2.09; 2.73, 2.42, P<0.05). There were no significant differences in serum levels of total cholesterol(TC), triglyceride(TG), superoxide dismutase(SOD) and glutathion peroxidase 4(GPX4) between the two groups (t=1.49, 1.00, -0.01, 0.59, P>0.05).@*Conclusion@#Twelveweek FATmax intensity exercise combined with dietary restriction could significantly improve body composition and dyslipidemia, prevent the occurrence of ferroptosis and liver oxidative damage in obese NAFLD college students,which could serve as a timely promotion and application of intervention for obese college students with NAFLD.

Comprehensive Analysis of Proteins and Their Phosphorylation in Milk-derived Exosomes From Different Species / 生物化学与生物物理进展

ObjectiveExosomes are microvesicles which could be secreted by all cell types with diameters between 30 and 150 nm. It was widely distributed in body fluids including blood, urine, and breast milk. Exosomes are considered as potential biomarkers and drug carriers by reason of containing nucleic acids, lipids, proteins and other bioactive molecules. Milk-derived exosomes have been widely used as drug delivery carriers to treat targeted diseases with a lower cost, higher biocompatibility and lower immunogenicity. Until now, there is no research about the milk-derived exosomes phosphorylation to reveal the difference of protein phosphorylation in different species of milk. To investigate the pathways and proteins with specific functions, phosphorylated proteomic analysis of milk-derived exosomes from different species is performed, and provide new ideas for exploring diversified treatments of disease. MethodsWhey and exosomes derived from bovine, porcine and caprine milk were performed for proteomics and phosphoproteomics analysis. The relationship between milk exosome proteins from different species and signaling pathways were analyzed using bioinformatics tools. ResultsA total of 4 191 global proteins, 1 640 phosphoproteins and 4 064 phosphosites were identified from 3 species of milk-derived exosomes, and the exosome proteins and phosphoproteins from different species were significantly higher than those of whey. Meanwhile, some special pathways were enriched like Fcγ-mediated phagocytosis from bovine exosomes, pathways related with neural and immune system from caprine exosomes, positive and negative regulation of multiple activities from porcine exosomes. ConclusionIn this study, the proteomic and phosphoproteomic analyses of exosomes and whey from bovine, porcine and caprine milk were carried out to reveal the difference of composition and related signaling pathways of milk exosome from different species. These results provided powerful support for the application of exosomes from different milk sources in the field of disease treatment.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Effects of Zhoufei Pingchuan Capsules on Th17/Treg Balance and Related Inflammatory Factors in Peripheral Blood of Patients with Stable Chronic Obstructive Pulmonary Disease with Lung-kidney Qi Deficiency Syndrome / 中国中医药信息杂志

Objective To investigate the effects of Zhoufei Pingchuan Capsules on the balance of peripheral blood helper T lymphocyte 17 cell/regulatory T lymphocyte cell(Th17/Treg)and related inflammatory factors in peripheral blood of patients with stable chronic obstructive pulmonary disease(COPD)with lung-kidney qi deficiency syndrome.Methods Totally 40 COPD patients were randomly divided into the study group and the control group,with 20 cases in each group.Another 20 cases were in the healthy group.The control group was given tiotropium bromide powder inhalation,18 μg/time,1 time/d,inhalation;on the basis of the control group,the study group was given Zhoufei Pingchuan Capsules,3 pills/time,3 times/d,orally.All patients were treated for 8 weeks.The healthy group was not given any intervention.Forced expiratory volume in one second(FEV1),FEV1/forced vital capacity(FEV1/FVC),maximum mid-expiratory flow(MMEF),carbon monoxide diffusing capacity/alveolar ventilation(DLCO/VA),arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),COPD assessment test(CAT)score,Th17/Treg ratio,cytokines interleukin(IL)-17,IL-22,IL-10,and transforming growth factor-β1(TGF-β1)were compared before and after treatment.Results Compared with before treatment,the lung function indexes(FEV1,FEV1/FVC,MMEF,DLCO/VA),blood gas indexes(PaO2,PaCO2)and CAT score in the study group after treatment were significantly improved(P<0.05).After treatment,the mean values of MMEF,DLCO/VA,PaCO2 and CAT score in the study group were better than those in the control group(P<0.05).Compared with before treatment,the levels of Th17,IL-17 and IL-22 in the study group were significantly lower,and the levels of Treg,IL-10 and TGF-β1 were significantly higher(P<0.05).After treatment,there were significant differences in Th17,Treg,IL-17,IL-22,IL-10 and TGF-β1 among the three groups(P<0.01).Further pairwise comparison showed that Th17 ranked in the order of high and low was control group>study group>healthy group,Treg in the order of high and low was healthy group>study group>control group,the levels of IL-17 and IL-22 in the order of high and low were control group>study group>healthy group,and the levels of IL-10 and TGF-β1 in the order of high and low were healthy group>study group>control group,with statistical significance(P<0.05).Conclusion Zhoufei Pingchuan Capsules can improve the lung function,arterial blood gas and symptom score of patients with lung-kidney qi deficiency syndrome in stable stage of COPD.Its mechanism may be related to regulating the balance of Th17/Treg,down-regulating the levels of Th17,IL-17 and IL-22,and up-regulating the levels of Treg,IL-10 and TGF-β1,in order to reduce airway inflammation and regulate immune homeostasis.

Bullying in professional sports: psychological needs of athletes.

BACKGROUND: This paper aimed to establish whether bullying in sports affects the satisfaction of such psychological needs as autonomy, competence, and relatedness in professional sports. METHODS: The instruments in this work were the Bullying Participant Behaviors Questionnaire (BPBQ), the Motivational Mediators Scale in Sport (EMMD), and the Psychological Needs Thwarting Scale (PNTS). The participants were 708 professional athletes. RESULTS: Comparison of EMMD and PNTS means unveiled that professional athletes with no bullying experience are more psychologically satisfied and less thwarted in all three dimensions (competence, autonomy, and relatedness). Among the group exposed to bullying, victims (18.92) and bullies (23.18) had the lowest needs in terms of competence, while bullies (26.14) and victims (20.10) experienced the lowest autonomy. The relatedness factor was most pronounced in victims' defenders (34.06) and least in victims (16.39). The lowest competence thwarting was found for outsiders and defenders, and the highest - among victims of bullying (18.12). But both bullies and their helpers had significantly higher scores than the other two roles. The need for autonomy, in turn, was least thwarted in outsiders and defenders, and most - in victims, as in the case of the relatedness subscale. CONCLUSIONS: The practical and scientific value of this work stem from the fact that it proves the negative impact of bullying on the satisfaction of basic psychological needs. The obtained findings can facilitate the development and implementation of updated educational programs and practices, leadership systems, as well as be conducive to the work of sports psychologists.

Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Evaluation for application of automatic detection of sperm head morphology based on deep learning / 临床检验杂志

Objective To design an automated detection protocol for morphological detection of sperm head based on deep learning and evaluate its efficiency,accuracy and reliability.Methods Fourteen pictures for each of 1 000 samples were analyzed by using the pre-trained YOLO target detection model and VGG16 classification model.At least 200 sperm were detected for each sample.Equal amount of samples were analyzed by manual microscope examination,and the efficiency,accuracy and correlation between the two methods were compared.Results The morphology of sperm heads which were manually classified but untrained was detected by pre-trained classification model,and the prediction accuracy reached to 95.5％.The detection time for clinical each sample was only 10 seconds,and its accuracy and efficiency were higher than those of manual microscope examination.The percentages of the sperms with normal morphology were significantly positively correlated(r=0.84,P＜0.01)in the detections of both the methods.Conclusion The detec-tion protocol proposed in this study can greatly improve work efficiency,and its reliability and accuracy exceed those of manual micro-scope examination.

ACT001 exerts anti-inflammatory and antioxidative activity to alleviate sepsis-induced acute lung injury through STAT1/CIITA/MHC- II pathway / 中国药理学通报

Aim This study aimed to assess the therapeutic potential of ACT001, a micheliolide derivative, in the treatment of acute lung injury ( ALI) induced by sepsis and investigate its pharmacological mechanisms. Methods At the animal level, an ALI model was established in mice through intraperitoneal injection of li-popolysaccharide (LPS). Subsequently, ACT001 was administered to the ALI-afflicted mice. The therapeutic effects of ACT001 were assessed by evaluating factors such as individual survival rate, lung inflammation, and pulmonary edema. At the cellular level, RAW264. 7 cells were stimulated with LPS to explore the pharmacological mechanism of ACT001. The study examined inflammatory response and oxidative stress levels, and proteomics analysis was conducted to investigate the underlying molecular mechanisms. Results At the animal level, ACT001 can improve the survival of mice with ALI, reduce lung inflammation, and reduce the levels of inflammatory cytokines in serum. At the cellular level, ACT001 promotes the polarization of RAW264. 7 cells toward an anti-inflammatory pheno-type by inhibiting MHC-II related pathways, inhibiting the production of NO and related inflammatory cytokines while increasing SOD content and scavenging ROS. Conclusions ACT001 exhibited the potential to alleviate ALI via its anti-inflammatory and antioxidative activity, mainly by inhibiting the STAT1/ CIITA/ MHC-II pathway. ACT001 holds promise as a novel therapeutic candidate for the treatment of ALI induced by sepsis.

Decompensation effectiveness and alveolar bone remodeling analysis of mandibular anterior teeth after preoperative orthodontic treatment in high-angle patients with skeletal class Ⅱ malocclusion / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the decompensation effectiveness and alveolar bone remodeling of mandibular anterior teeth after preoperative orthodontic treatment in high-angle patients with skeletal class Ⅱ malocclusion using lateral cephalogram and cone-beam computed tomography (CBCT).@*METHODS@#Thirty high-angle patients with skeletal class Ⅱ malocclusion who had received preoperative orthodontic treatment and orthognathic surgery in Peking University School and Hospital of Stomatology between Ja-nuary 2017 and August 2022 and had taken lateral cephalogram and CBCT before and after preoperative orthodontic treatment were selected. Items were measured with lateral cephalogram including: The lower central incisor (L1)-Frankfort plane angle (L1-FH), the L1-mandibular plane angle (L1-MP), the L1-nasion-supramental angle (L1-NB) and the vertical distance from the incisal edge of lower central incisor to NB line (L1-NB distance), etc. The incidence of dehiscence/fenestration and the length of dehiscence at labial side (d-La) and lingual side (d-Li) were measured using CBCT. Pearson correlation analysis was used to evaluate the correlation between the changes of d-Li of L1 and age, duration of preoperative orthodontic treatment and the cephalometric measurements before preoperative orthodontic treatment to screen out risk factors affecting the periodontal risk of preoperative orthodontic treatment in high-angle patients with skeletal class Ⅱ malocclusions.@*RESULTS@#After preoperative orthodontic treatment, L1-FH, L1-MP, L1-NB and L1-NB distances changed by 11.56°±5.62°, -11.13°±5.53°, -11.57°±5.43° and (-4.99±1.89) mm, respectively, and the differences were all statistically significant (P < 0.05). Among the 180 measured mandibular anterior teeth, 45 cases with labial dehiscence/fenestration before preoperative orthodontic treatment (T0) had no longer labial dehiscence/fenestration after preope-rative orthodontic treatment (T1); 142 cases without lingual dehiscence/fenestration at T0 had lingual dehiscence/fenestration at T1. After preoperative orthodontic treatment, the d-La of lower lateral incisors (L2), lower canines (L3) and lower anterior teeth (L1+L2+L3) decreased by (0.95±2.22) mm, (1.20±3.23) mm and (0.68±2.50) mm, respectively, and the differences were statistically significant (P < 0.05); the d-Li of L1, L2, L3 and L1+L2+L3 increased by (4.43±1.94) mm, (4.53±2.35) mm, (3.19±2.80) mm and (4.05±2.46) mm, respectively, and the differences were statistically significant (P < 0.05). The increase of d-Li of L1 was positively correlated with L1-FH (r=0.373, P=0.042).@*CONCLUSION@#This study showed that high-angle patients with skeletal class Ⅱ ma-locclusion could achieve ideal decompensation effect of mandibular anterior teeth after preoperative orthodontic treatment with bilateral mandibular first premolars extracted, but the lingual periodontal risk of mandibular anterior teeth was increased. This risk could be correlated to L1-FH before preoperative orthodontic treatment, which should be paid more attention in the design of orthodontic-orthognathic surgical treatment.

Study on static parameters of internal nasal valve in 3-dimensional model of nasal cavity space / 中华耳鼻咽喉头颈外科杂志

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.

Application of high-density polyethylene implants in adult cleft lip and palate nasal deformity and dysfunction / 中华耳鼻咽喉头颈外科杂志

Objective: Through the use of high-density polyethylene implants in adults with cleft lip and palate nasal deformities and abnormal functions, to evaluate the clinical effect of postoperative patients on improving nasal shape and symptoms. Methods: A retrospective study of 12 patients with nasal deformities after cleft lip and palate surgery in the Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine from January 2018 to January 2022 was completed, including 7 males and 5 females, with the age ranging from 18 to 29 years. All the patients underwent nasal deformity correction, and nasal septum correction was performed if necessary. High-density polyethylene implants (MEDPOR/Su-Por) were used intraoperatively. Follow-up for at least 6 months was performed to measure the relevant appearance indicators and subjective Visual Analog Scale (VAS) scores, and to compare the clinical effects before and after surgery. SPSS 22.0 software was used for statistical analysis. Results: Before and after surgery, the average VAS score of nasal obstruction decreased by (4.83±0.94) points; the average VAS score of appearance satisfaction increased by (3.92±1.08) points; the height of nasal columella was increased by (1.79±0.78)mm; the height of nasal tip was increased by (2.79±1.50)mm; the height of ipsilateral nostril was increased by (1.83±0.62)mm; the width of the ipsilateral nasal floor was reduced by (0.42±0.47)mm. All of above were statistically significant (all P<0.05). Conclusion: High-density polyethylene implants can effectively improve the shape and function of the nose in operations related to cleft lip and palate nasal deformity and abnormal functions, and are an ideal synthetic material.

CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer / 医学前沿

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Analysis of the effectiveness of sequential plate internal fixation in correction of Madelung deformity after ulnar osteotomy and shortening / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening.@*METHODS@#The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded.@*RESULTS@#After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case.@*CONCLUSION@#Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.

Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study / 中华内科杂志

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Characteristics of digestive system symptoms and abdominal computed tomography imaging of patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant / 中华消化杂志

Objective:To investigate the characteristics of digestive system symptoms and its relation with the time of nucleic acid continuous positive in population infected with severe acute respiratory syndrome coronavirus 2 Omicron variant, and to analyze the abdominal computed tomography (CT) features of patients infected with Omicron variant.Methods:From April 11 to May 23, 2022, a questionnaire survey was conducted in patients infected with Omicron variant admitted to the Shanghai National Convention and Exhibition Center Fangcang Hospital. The questionnaire included basic information, the start time of nucleic acid positive, respiratory symptoms, digestive system syptoms and outcomes, etc.Combined with the clinical data, the relation between digestive tract symptoms and the time of nucleic acid continuous positive were analyzed. Thoracic and abdominal CT were performed for patients with continuous positive nucleic acid results ≥10 d, and the relationship between the abdominal CT imaging characteristics and the time of nucleic acid continuous positive was analyzed. Independent sample t-test and multivariate logistic regression were used for statistical analysis. Results:A total of 4 360 valid questionnaires were collected, including 2 475 males and 1 885 females, with a hospital stay of (6.8±4.9) d. Among the 4 360 patients, 1 979 patients (45.4%) had gastrointestinal symptoms such as loss of appetite, abdominal discomfort or pain, constipation and diarrhea. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms was (7.4±5.5) d, which was longer than that of patients without gastrointestinal symptoms (6.5±3.6) d, and the difference was statistically significant ( t=3.78, P<0.001). During the isolation period in the Fangcang Hospital, the time of nucleic acid continuous positive in patients with complete remission of digestive tract symptoms was shorter than that of patients with no remission of digestive tract symptoms ((7.3±5.2) d vs. (8.5±5.7) d), and the difference was statistically significant ( t=2.25, P=0.025). The results of multivariate logistic regression analysis showed that the combination of gastrointestinal symptoms was an independent risk factor for continuous positive nucleic acid result ≥10 d ( OR=1.316, 95% confidence interval 1.294 to 2.205, P=0.046). Among the 299 patients with continuous positive nucleic acid results≥10 d, 187 cases (62.5%) had gastrointestinal symptoms, and 146 cases (48.8%) had abdominal CT findings of thickening of the gastroduodenal wall, thickening of the small intestinal wall, indistinct mesenteric vessels of the small intestine, and dilatation and pneumatosis of the colon. In patients with continuous positive nucleic acid results ≥10 d, abdominal CT indicated that patients with gastrointestinal imaging changes had a longer time of nucleic acid continuous positive than those without gastrointestinal imaging changes ((16.0±2.8) d vs. (13.0±2.1) d), and the difference was statistically significant ( t=2.62, P=0.009). Conclusions:Digestive system symptoms are common in patients infected with Omicron variant. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms is longer than those without gastrointestinal symptoms. Some patients may have gastrointestinal lesions on abdominal CT.

Curative effect of wide pedicled double-vessel flap of posterolateral calf in repair of soft tissue defect in hind foot / 中华显微外科杂志

Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.

The characteristics of stereoelectroencephalography in drug-resistant epileptic spasms / 中华实用儿科临床杂志

Objective:To analyze the characteristics of stereoelectroencephalography (SEEG) in children with drug-resistant epileptic spasms (ES), and to explore the surgical strategy of children with spastic seizure under the guidance of SEEG.Methods:The clinical data of 156 children with ES who were preoperatively evaluated in the Department of Neurosurgery Ward 3, Tsinghua University Yuquan Hospital from January 2014 to December 2021 were retrospectively reviewed.All children were evaluated in the second stage of stereotactic electrode placement after a non-invasive preoperative evaluation.The characteristics of intracranial EEG, surgical strategy and prognosis were analyzed.Results:A total of 19 eligible children were included, involving 13 boys and 6 girls.The age of first onset and surgical age of them ranged 1 month to 4 years, and 2 years to 13 years, respectively.The SEEG was divided into 3 types in children with ES at the onset.Five children were SEEG type A, presenting with the focal seizure discharges at the beginning and a gradual propagation to widespread fast-wave bursts.Ten children were SEEG type B, presenting a focal leading spike followed by diffused fast-wave bursts.Four children were SEEG type C, presenting a diffuse fast wave rhythm onset.Although some electrode discharges appeared slightly " leading", they covered more than one brain region.After focal resection or thermocoagulation, 13/19 patients did not have the onset of seizures, and 5/19 and 8/19 were graded as SEEG type A, and B, respectively.During the intermittent period of SEEG attacks in children with SEEG type A and B, a significant phenomenon of focal epileptic discharge consistent with the onset of the attack was observed, and surgical removal of these areas effectively controlled spastic seizures.Conclusions:Epileptic spasms may be triggered by a focal neocortical discharge.Intracranial EEG showed that the focal seizure onset evolves into spasm or a focal " leading spike" is a good indicator of surgical prognosis.

Reinforce revealing missing heritability in the gene of inherited retinal diseases / 中华眼底病杂志

Inherited retinal diseases (IRD) are a group of genetic disorders with high genetic and clinical heterogeneity. Genetic diagnosis has become one essential method for patients with IRD in their clinical management. So far, about 30% of the patients with IRD cannot get molecular diagnosis (no pathogenic variant detected or only mono-allele variant identified in AR genes) using target or whole exome sequencing. Most missing heritability or variants for these patients were variants located in no-coding regions (deep intron or promoter regions) and structure variants of the known IRD genes. It is more challenge to reveal this kind of missing variants, which need using whole genome sequencing combined with other cellular or molecular assays.