Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Although indigenous malaria has been eliminated in Wuhan since 2013,imported malaria remains a potential threat as an infectious source of local malaria transmission.The epidemiological and clinical characteristics of imported malaria are particularly important in areas where local malaria has been eliminated.This study was aimed at analyzing the epidemiological and clinical characteristics of imported malaria in Wuhan from 2012 to 2019,to provide a basis for further improving the preven-tion and control of imported malaria.Patients in Wuhan diagnosed with imported malaria from January 1,2012,to December 31,2019,were included in this study.A case-control study was con-ducted to analyze the features of patients with severe malaria.Uni-variate and multivariate logistic regression was used to identify risk factors for prolonged hospital length of stay(LOS).Among 229 imported malaria cases,212(92.6％)were in Chinese citizens,and most cases were in men(96.5％).The gender ratio is 28:1,and the age of cases is mainly concertrated between 18 and 50 years old(89.1％).More than 80％of patients were mi-grant workers,and most cases were infections from African countries(92.6％).Plasmodium falciparum(80.8％)was the dominant species.Fifty-three severe malaria cases were identified during the study period.Compared with uncomplicated cases,severe cases tended to occur in patients with no history of malaria(P=0.008),patients infected with Plasmodium falciparum(P=0.009),and patients who were initially misdiagnosed(P＜0.001).The median LOS was 6 days,and the species of infec-tion(Plasmodium falciparum),the use of antimalarial drugs(group B),antipyretic time(longer than 3 days),and the turn-around time of blood smear microscopy(longer than 3 days)were significantly associated with longer LOS(all P＜0.05).Al-though malaria has been eradicated in Wuhan for many years,imported cases continue to pose a threat.Efforts should be made to strengthen malaria knowledge education for outbound personnel.Additionally,medical institutions must enhance diagnosis and treatment capabilities for malaria,and adhere to standardized treatment processes,and the development of drug resistance and occurrence of severe malaria must be prevented.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective The characteristics of supramolecular"imprinting template"of volatile oil of Curcuma kwangsiensis and Curcuma phaeocaulis were analyzed and studied based on the supramolecular"qixi"theory of Chinese materia medica combined with chemometrics.Methods The volatile oil of C.kwangsiensis and C.phaeocaulis were extracted by steam distillation,and the fingerprint and composition information of each batch were obtained by GC-MS.Total statistical moment method was used to compare the imprinting characteristics of the"imprinting template"of C.kwangsiensis and C.phaeocaulis.The core index(CI)of each batch of essential oil of C.kwangsiensis and C.phaeocaulis was calculated,and the topological characteristics of types of"imprinting template"of C.kwangsiensis and C.phaeocaulis were compared by chemometrics.Results There was no significant difference in the extraction rate of volatile oil between C.kwangsiensis and C.phaeocaulis.The average values of total zero order moment(AUCT)were(1.907±0.177)×108,(1.979±0.413)×108 μV·s,respectively,showing that there was no significant difference in the total content of volatile oil between the two groups.The mean values of the total first order moment(MCRTT)were(30.969±0.962)and(33.198±0.409)min.The average value of total second order moment(VCRTT)was(56.176±11.368)and(43.891±4.113)min2,respectively,indicating that there were significant differences in the content ratio and species of volatile oils between the two groups.The similarity of total statistical moments of C.kwangsiensis and C.phaeocaulis was mostly lower than the defined value,indicating that the chemical composition and composition ratio of the volatile oil were different.Principal component analysis and orthogonal partial least squares discriminant analysis could obviously divide C.kwangsiensis and C.phaeocaulis into two categories.Through the analysis of P value and VIP value,the CI values of Xvp 4th order,Xvpc 5th order,Xvpc 6th order,Xvpc 7th order,Xvc 3rd order,Xvpc 4th order were the main difference values of C.kwangsiensis and C.phaeocaulis.Conclusion Through the characterization of"imprinting property"and"topological characteristics"of the supramolecular"imprinting template"and combining with chemometric analysis,it is possible to successfully distinguish C.kwangsiensis and C.phaeocaulis,and find the different CI values between two"imprinting templates".

Objective:To evaluate the cardiac morphological and functional parameters of patients with persistent atrial fibrillation (per-AF) and paroxysmal atrial fibrillation (PAF) using two-dimensional speckle tracking echocardiography (2D-STE) and real-time three-dimensional echocardiography (RT-3DE), and to explore their predictive value for the occurrence and progression of atrial fibrillation.Methods:A retrospective study was conducted on 30 per-AF patients (per-AF group), 30 PAF patients (PAF group) and 25 non-AF subjects (control group) who underwent echocardiography at Wuhan University People′s Hospital from May 2022 to May 2023. The left/right atrial longitudinal strain of reservoir, conduct and contraction (LASr/RASr, LAScd/RAScd, LASct/RASct), and calculated left atrial stiffness (LASI) were assessed by 2D-STE. Three-dimensional left and right atrial maximum volume index (LAVImax/RAVImax), minimum volume index (LAVImin/RAVImin) and emptying fraction (LAEF/RAEF) were obtained by RT-3DE. Then, patients with atrial fibrillation were divided into the normal LAVI group and enlarged LAVI group, and the differences of atrial strain among each group were compared. ROC curve was used to evaluate the overall diagnostic efficiency and cutoff values of ultrasonic parameters in patients with normal volume of atrial fibrillation. Finally, a multivariate Logistic regression model was established to identify the ultrasonic parameters associated with the occurrence and progression of different types of atrial fibrillation.Results:①Structurally, LAD, RAD and RAVImin in control, PAF and per-AF groups increased gradually, while LAEF and RAEF decreased gradually (all P<0.05). ②In terms of strain, LASr in control, PAF and per-AF groups decreased gradually (all P<0.05); Compared with the control group, LAScd, RASr and RAScd in PAF and per-AF groups were significantly decreased, and LASct and RASct in PAF group were significantly decreased (all P<0.05). ③Compared with the normal LAVI group, the LASr, LAScd and LASct in the enlarged LAVI group were significantly decreased, while LASI was significantly increased (all P<0.05); Compared with control group, the left and right atrial strain parameters in LAVI normal group were decreased, and LASI was increased (all P<0.05). The atrial strain parameter ROC was constructed in all subjects with normal left atrial volume, and RASr was the most sensitive indicator.④Multi-factor Logistic regression analysis showed that LAVImin and RASr were the influence factors of PAF ( OR=1.521, 0.907; 95% CI=1.173-1.972, 0.825-0.998; P=0.002, 0.044), LASr was the influence factor of pre-AF ( OR=0.858, 95% CI=0.802-0.917, P<0.001). Conclusions:2D-STE and RT-3DE can be used to evaluate the structural and functional changes of both atria, especially LAVImin, LASr and RASr, which have certain predictive value for the occurrence and progression of atrial fibrillation.

Objective:To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED).Methods:Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed.Results:Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases.Conclusions:CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Objective: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. Methods: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. Results: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. Conclusion Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective:To quantitatively evaluate and compare the morphology and dynamics parameters of mitral valve devices in patients with atrial functional mitral regurgitation (AFMR) and ventricular functional mitral regurgitation (VFMR) by real-time three-dimensional ultrasound, in order to provide theoretical basis for diagnosis and clinical treatments of the two types of regurgitation patients.Methods:A retrospective study was conducted on 20 AFMR patients (AFMR group) and 20 VFMR patients (VFMR group) who underwent transesophageal echocardiography at Wuhan University People′s Hospital from May to November 2022. Additionally, 20 patients who underwent transesophageal echocardiography at our hospital during the same period due to patent foramen ovale or non cardiac surgery monitoring were selected as the control group. All subjects were measured mitral annulus anteroposterior diameter (AP diameter), anterolateral posteromedial diameter (ALPM diameter), anteroposterior diameter/anterolateral posteromedial diameter (AP/ALPM), commissural width (CW), annular area (AA), annular circumference (AC), annular height (AH), coaptation depth (CD), tenting volume (TV), non-planar angle (NPA) and posterior leaflet angle at isovolumic relaxation time, early diastole, mid diastole, late diastole, isovolumic contraction time, early systole, mid systole, and late systole. The total change rate and systolic change rate of the above parameters were calculated, the differences in structure and dynamic changes of the mitral valve device among three groups were compared, and the correlations between the change rate of mitral annular parameters and left ventricular long axis strain (GLS) were analyzed.Results:①The GLS of three groups were as follows: control group>AFMR group>VFMR group, and the differences between the groups were statistically significant (all P<0.05). ②Static structure: The AP diameter, ALPM diameter, AA, AC, and total leaflet area (TLA) of the AFMR group and VFMR group were significantly larger than those of the control group (all P<0.05), but there was no statistically significant difference between the AFMR group and VFMR group (all P>0.05). Compared with the other two groups, the TV, CD, and posterior leaflet angle of the VFMR group were significantly increased, exhibiting the mitral valve tethering; the control group had the largest AH/CW and the deepest saddle shape; the AFMR group had the smallest TLA/AA and the least mitral valve remodeling; there was no statistically significant difference in the junction area among the three groups (all P>0.05). ③Dynamic changes: AP diameter, ALPM diameter, AA and AC in the control group showed regular changes throughout the cardiac cycle, gradually decreased from isovolumic relaxation time to late diastole, and gradually increased from isovolumic contraction time to late systole; The changes in the above parameters in the AFMR and VFMR groups appeared more disordered. In addition, compared with the control group, the total change rate and systolic change rate of AP diameter in the AFMR group were significantly reduced, but the total change rate of ALPM diameter was significantly increased (all P<0.05). ④The total change rate of AA, ALPM diameter and AP diameter were moderately correlated with GLS ( r=0.353, P=0.006; r=-0.304, P=0.018; r=0.300, P=0.020), while the systolic change rate of posterior leaflet angle was weakly correlated with GLS ( r=0.267, P=0.039). Conclusions:There are differences in the morphology and dynamics parameters of mitral valve device in patients with AFMR and VFMR.Different clinical strategies can be used for the two kinds of functional mitral regurgitation.

OBJECTIVE: To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture. METHODS: A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T₂ fracture, 1 case of T₃ fracture, 3 cases of T₄ fracture, 3 cases of T₅ fracture, and 7 cases of T₆ fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T₁ fracture, 5 cases of T₄ fracture, 2 cases of T₅ fracture and 9 cases of T₆ fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups. RESULTS: Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364). CONCLUSION Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.
Female ; Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Robotics ; Blood Loss, Surgical ; Bone Cements ; Retrospective Studies ; Thoracic Vertebrae/surgery*