Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

Innate and adaptive immune responses initiated by infection depend on recognition and control of pathogens by macrophages,dendritic cells,T cells and so on.Notch signaling pathway is a highly conserved pathway,which is activated by interac-tion of receptors and ligands,thus coordinating important life processes of cells.At present,it has been confirmed that Notch signaling pathway is involved in development,differentiation,maturation and activation of many kinds of immune cells,and plays an important role in infectious diseases.In this review,we mainly focus on the role of Notch signaling pathway in immune regulation during different pathogens infection and its interaction with other signaling pathways.Additionally,therapeutic methods and challenges of developing Notch signaling as a target in infectious diseases are also discussed.

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg^-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

Macrophage as a crucial component of innate immunity, plays an important role in inflammation and infection immunity. Notch signal pathway is a highly conserved pathway, which regulates cellular fate and participates in numerous pathological processes. At present, a lot of literature has confirmed the role of Notch signaling in regulating the differentiation, activation and metabolism of macrophage during inflammation and infection. This review focuses on how Notch signaling promotes macrophage pro-inflammatory and anti-infective immune function in different inflammatory and infectious diseases. In this regulation, Notch signaling interact with TLR signaling in macrophages or inflammatory-related cytokines including IL-6, IL-12, and TNF-α. Additionally, the potential application and challenges of Notch signaling as a therapeutic target against inflammation and infectious diseases are also discussed.
Humans ; Signal Transduction ; Macrophages ; Cytokines/metabolism* ; Inflammation/metabolism* ; Communicable Diseases ; Receptors, Notch/metabolism*

Objective:To investigate the prevalence of influenza, pneumococcal, hepatitis B virus (HBV), human papillomavirus (HPV), and varicella zoster virus (VZV) vaccination in patients with systemic lupus erythematosus (SLE), and to analyze the factors related to vaccination.Methods:Data were obtained from 1 203 patients with SLE, via a multi-center web-based survey using an online questionnaire. Data about their social conditions, clinical presentations, willingness for being vaccinated, vaccination within 5 years were collected. Demographic data were shown by descriptive analysis. Chi-square and logistic regression analysis were used to assess the power of related indexes as predictors of vaccination.Results:The vaccination rates of influenza, pneumococcal, HBV, HPV, and VZV were 5.49% (66/1 203), 0.66% (8/1 203), 2.08% (25/1 203), 3.82% (46/1 203), and 0.17% (2/1 203), respectively. Data analysis showed that higher education ( χ2=30.94, P<0.001) and higher income ( χ2=10.70, P=0.001) had greater effects on influenza vaccination. There was a relationship between HPV vaccination and higher education ( χ2=20.96, P<0.001), higher income ( χ2=20.56, P<0.001), younger age ( χ2=8.54, P=0.001), and single ( χ2=5.63, P=0.018). Male ( χ2=10.27, P=0.001) and higher education ( χ2=4.52, P=0.034) were associated with HBV vaccination. The multivariate logistic regression analysis revealed that higher education [ OR (95% CI)=2.14 (1.10, 4.18), P=0.026], having children under 18 years-old [ OR(95% CI)=1.802(1.02, 3.18), P=0.042], and hydroxychloroquine usage [ OR(95% CI)=2.55(1.06, 6.15), P=0.037], had a positive correlation with influenza vaccination. Male [ OR(95% CI)=4.24(1.37, 13.08), P=0.012], had an impact on HBV vaccination. The factors related to HPV vaccination included age <45 [ OR (95% CI)=0.93(0.89, 0.97), P=0.001], higher education [ OR(95% CI)=2.28(1.11, 4.65), P=0.024], higher income [ OR(95% CI)=2.68(1.32, 3.41), P=0.006] and the usage of immunosuppressive agents [ OR(95% CI)=1.92(1.03, 3.59), P=0.041]. Conclusion:The prevalence of vaccination in patients with SLE is low. Patients with higher education and income are more likely to being vaccinated.

Objective:To investigate the clinical characteristics of vasa previa (VP) with low-lying placenta (LP).Methods:A retrospective case-control study was conducted on pregnant women with VP who delivered at Guangzhou Women and Children's Medical Center from January 2015 to August 2021. According to the status of LP, these cases were classified into VP with LP (VP+LP) and VP without LP (VP-LP) group. The cases diagnosed with placenta previa (PP, n=128) during the same period were collected as control. Maternal-fetal clinical characteristics and outcomes were compared among the three groups using t-test, Mann-Whitney U test, and Chi-square test (or Fisher's exact test). Results:During the study period, 116 VP cases were diagnosed, accounting for 0.085% (116/136 450) of all deliveries. Apart from one case of intrauterine death caused by non-VP reasons in the third trimester, there were 64 in the VP+LP group and 51 in the VP-LP group. VP+LP cases accounted for about 2.9% (64/2 219) of all the cases with PP or LP. The proportions of multiparae and women with a history of cesarean section were significantly higher in the VP+LP group than in the VP-LP group [62.5% (40/64) vs 39.2% (20/51), χ 2= 6.17, P=0.013; 31.3% (20/64) vs 13.7% (7/51), χ 2= 4.85, P=0.028]. Besides, a rare type of VP (type Ⅲ) was only found in the VP+LP group (9.4%, 6/64). The median gestational age at first diagnosis by prenatal ultrasound was significantly larger in the VP+LP group than in the VP-LP group [28.3 (23.6-31.7) vs 23.9 (23.3-25.9) weeks, Z=2.61, P=0.007]. There was no significant difference in the incidence of antepartum hemorrhage between the two groups. In contrast, the amount of postpartum hemorrhage was significantly increased in the VP+LP group [550 (436-732) vs 420 (300-540) ml, Z=3.37, P=0.001]. Compared with the VP-LP group, the VP+LP group showed a lower incidence of lower neonatal Apgar score (<7 at 5 min) and hypoxic-ischemic encephalopathy [0.0%(0/64) vs 6.9%(4/58), 0.0%(0/64) vs 8.6% (5/58), Fisher's exact test, both P<0.05]. No neonatal death was reported in the VP+LP and VP-LP groups. No significant difference in the incidence of antepartum hemorrhage was found between the VP+LP group and the PP group. Still, the median time at delivery was earlier [36.0 (34.3-36.9) vs 37.0 (35.7-37.3) weeks, Z=3.79, P<0.001], and the incidence of abnormal fetal heart rate was higher [10.9% (7/64) vs 3.1% (4/128), Fisher's exact test , P=0.044] in the VP+LP group. Furthermore, the neonatal NICU admission rate and the incidence of respiratory distress syndrome were significantly higher in the VP+LP group than in the PP group [36.4% (24/66) vs 12.1% (16/132), χ 2= 16.04, P<0.001; 25.8% (17/66) vs 12.1% (16/132), χ 2= 5.89, P=0.015]. Conclusions:For VP+LP cases, there might be an additional type (type Ⅲ VP). Patients with VP+LP would have more blood loss within 24 h after delivery and a higher risk of adverse neonatal outcomes. Intensive attention should be paid to those diagnosed with LP during the third trimester to identify any VP.

OBJECTIVES: At present, the research on clear aligner of molar distalization mainly focuses on the upper jaw, while the research on mandibular molars is few.This study aims to evaluate the therapeutic effect of mandibular molars distalization with clear aligner via cone beam CT (CBCT) and Dolphin software. METHODS: Twenty cases of mandibular molars with clear aligner were included according to the inclusion and exclusion criteria. CBCT was taken before treatment (T0) and when the first molar was moved in place (T1). Dolphin software was used to measure the effectiveness of molar distalization. Three-dimensional changes in direction and the impact on the incisors and facial soft and hard tissues were evaluated. RESULTS: The effective rates of crown and root distalization of the second and first mandibular molars were 74%, 49%, and 71%, 47%, respectively. The second and first molars were both the distal buccal cusp with the largest distalization [(2.15 ± 0.91) mm and (1.85±1.09) mm], respectively, with significant difference between the T0 and T1 ( CONCLUSIONS Clear aligner can effectively move mandibular molars farther, the crown is more effective than the root, and it is tilted. The second mandibular molar is more effective than the first mandibular molar in its distant displacement and three-dimensional changes. Molar distalization causes minor changes in mandibular incisors and facial soft and hard tissues.
Cephalometry ; Maxilla ; Molar ; Orthodontic Appliances, Removable ; Tooth Movement Techniques

OBJECTIVE: To study the genotype and phenotype of fetuses with 22q11.2 microdeletion and other abnormalities such as cardiac malformation and cleft palate. METHODS: Fetal ultrasound was carried out at 12 weeks to 20 to 24 weeks of gestation. After excluding the chromosomal karyotype abnormality, single nucleotide polymorphism (SNP) array was used to detect copy number variations of 5 fetuses with heart development abnormality or other structural abnormalities. The fetus with 22q11.2 microdeletion and its parents were also subjected to multiplex ligation-dependent probe amplification (MLPA) assay. RESULTS: SNP array analysis showed that the 5 fetuses had all carried a 2.27-3.02 Mb deletion of the 22q11.2 region. MLPA assay confirmed that LCR22-A-B was involved in all cases, and that all deletions were de novo in origin. CONCLUSION It is of great significance to exclude 22q11.2 microdeletions in fetuses with cardiac malformations. The deletion regions of these fetuses are similar but different, and the phenotypic difference is related to their genotypes.

Objective: To evaluate the effect of cervical lifting suture in treatment of placenta previa with increta and percreta. Methods: From January 2016 to June 2017, 65 cases (0.78%, 65/8 322) were diagnosed placenta previa with increta and percreta by prenatal ultrasonic score system and confirmed by intraoperative findings in the department of obstetrics and gynecology of Peking University Third Hospital. Totally 62 cases (0.75%, 62/8 322) were included, because 3 cases underwent hysterectomy with placenta in situ. According to ultrasonic score system, 62 cases were divided into two groups, score 5-9 group (n=42, 67.7%) and score≥10 group (n=20, 32.3%) , cervical lifting suture techniques were all performed in cesarean sections. Demographic and clinical data were collected and compared. Results: (1) There were no significant differences between two groups in age, gravidity, parity, cesarean section history ratio and gestational week of termination (all P>0.05) . (2) In score≥10 group, the median intraoperative bleeding volume was 4 000 ml (1 200-13 000 ml) , while in score 5-9 group, it was 1 600 ml (700-10 000 ml) , intraoperative blood transfusion volume was 2 000 ml (800-8 800 ml) in score≥10 group, while 1 200 ml (0-8 000 ml) in score 5-9 group. The median operation time was 240 minutes (108-1 200 minutes) in score≥10 group, significantly higher than that in score 5-9 group, which was 135 minutes (69-335 minutes; all P< 0.05). In 8 cases for hysterectomy (12.9%,8/62) , 3 cases in score 5-9 group, 5 cases in score≥10 group. (3) In score≥10 group, the rate of postoperative ICU registration was 80% and mean hospitalization time was (6.3±1.7) days, were significantly different, compared with those in score 5-9 group, which were 26%, (4.9±1.9) days. No serious postpartum complications were found in both groups, and there were no significant differences in Apgar score and weight of newborns (all P>0.05) . Conclusion Cervical lifting suture in placenta previa with increta and percreta could significantly reduce postpartum hemorrhage and retain uterine.

Objective To explore the value of ultrasound scoring system in predicting the type and risk of placenta accreta.Methods Clinical data of 180 placenta accreta patients who delivered in the Peking University Third Hospital between January 2005 and November 2014,were retrospectively analyzed.Prenatal ultrasonographic features were analyzed,including position and thickness of the placenta,disappearance of hypoechoes in posterior placenta,continuousness of bladder line,existence of lacuna,condition of the subplacental vascularity,completeness of cervical morphology,existence of cervical sinus,and history of cesarean section.A score of 0,1 or 2 was given to each item,and a sum-up was calculated for each patient.The cut-off scores of patients with placenta accreta,placenta increta and placenta percreta were calculated by receiver operating characteristic carve,respectively.At the same time,blood loss and hysterectomy rate were compared among the three groups.Variance analysis,rank sum or Chi-square tests were used for statistical analysis.Results Among the 180 cases,there were 115 cases of placenta accreta,38 of planceta increta and 27 of placenta percreta.Placenta increta and percreta were defined as the severe type.Blood loss in placenta accreta was lower than in the severe type [200 (100-4 000) ml vs 3 025 (100-15 000) ml,P＜0.01].There was no difference in blood loss between patients with placenta increta or percreta (P=0.350).No hysterectomy was performed for patients with placenta accreta,the rate being lower than in the severe type [0 vs 29.2％ (19/65),P＜0.01].Among the severe type,18.4％ (7/38) of the placenta increta patients underwent hysterectomy,the rate being lower than in placenta percreta patients [44.4％ (12/27),P＜0.01].The score in placenta accreta was lower than in the severe type [(1.88± 1.45) vs (7.01 ±2.15) scores,P＜0.01].In the severe type,the score in placenta increta was lower than in placenta percreta [(6.08 ± 2.62) vs (8.74 ± 2.75),P＜0.01].The receiver operating characteristic curve showed that the cut-off score of placenta accreta and the severe type was 5 [area under the curve (AUC)=94.3％,the score ≥ 4.5,the sensitivity=81.5％,and the specificity=95.7％],the cut-off score of placenta accreta and increta was 3 (AUC=91.1％,score ≥ 2.5,the sensitivity=92.1％,and the specificity=75.7％),and the cut-off score of placenta increta and percreta was 10 (AUC=74.6％,score ≥ 9.5,the sensitivity=55.6％,and the specificity=89.5％).Conclusions Ultrasound scoring system is effective in assessing types of placenta accreta and predicting its associate risks,and alerting the possibility of hysterectomy.It also facilitates preoperative planning and guides physicians in formulating subsequent treatment plans.Placenta accreta and the severe type (placenta increta and percreta) can be distinguished by cut-offscores ≥ 5,and a score ≥ 10 implies a higher risk of placenta percreta.