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.

Objective: To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children. Methods: A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations. Results: The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05). Conclusion Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.

Objective To analyze the relationship of serum S100 calcium binding protein A4(S100A4)and pentraxin-3(PTX3)levels with left atrial appendage thrombosis in patients with NVAF.Methods A total of 120 elderly NVAF patients treated in our hospital from March 2020 to March 2023 were enrolled in this study.According to their echocardiograms,they were divided into a left atrial appendage thrombosis group(40 cases)and a non-thrombosis group(80 cases).Serum S100A4 and PTX3 levels were detected.Spearman correlation analysis was applied to ana-lyze the relationship between serum S100A4 and PTX3 levels and left atrial appendage thrombo-sis.Logistic regression analysis was conducted to analyze the factors affecting left atrial appendage thrombosis.Results The serum levels of S100A4 and PTX3 were higher in the thrombosis group than the non-thrombosis group(P＜0.01).The serum levels of S100A4 and PTX3 were positively correlated with left atrial appendage thrombosis(r=0.497,P=0.000;r=0.555,P=0.000).Heart failure,CHA2DS2-VASc score,B-type natriuretic peptide,uric acid,S100A4 and PTX3 were risk factors for left atrial appendage thrombosis in NVAF patients(P＜0.05,P＜0.01).Combination of serum S100A4 and PTX3 in predicting left atrial appendage thrombosis formation in NVAF patients had an AUC value of of 0.949(95％CI:0.893-0.981).Conclusion Serum S100A4 and PTX3 levels are increased in NVAF patients,they are related to left atrial appendage thrombosis,and their serum levels have certain predictive value for left atrial appendage thrombosis.

Pan-vascular medicine is an emerging discipline focusing on atherosclerotic diseases,with the concept of multidisciplinary integration,emphasizing on exploring the mechanism of disease development from the whole of the organism's structure and function.At present,the basic mechanism system of pan-vascular diseases has yet to be perfected.The pan-vascular concept is highly compatible with the idea of Chinese medicine that focuses on the overall view.Deficiency of all qi is the root cause of pan-vascular diseases,while phlegm,blood stasis,and water-dampness and other tangible evils stagnate in the veins and channels as the symptoms of the disease,therefore,the disease mechanism can be highly summarized as"stagnation due to qi deficiency".Deficiency leads to the stagnation,blocking the veins and channels,and the deficiency worsens due to the stagnation and then damages the veins and channels,thus,it develops into a disease.Based on the theory of"stagnation due to qi deficiency",this paper takes endothelial cell dysfunction as the entry point of pan-vascular diseases,and considers that low endothelial cell immunity is the initiating factor of pan-vascular diseases,and that the widespread persistence of microinflammatory state is the key pathology to pan-vascular diseases.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory,identity awareness,immediate sensation,and motor control.This article documents a case of the disorder presenting with an onset of depressive mood,diminished interest,and facial tics,subsequently accompanied by intermittent fainting spells with limb convulsions.Despite multiple consultations in both general hospitals and psychiatric settings,and despite treatment with various antidepressants and antiepileptic medications,the patient's symptoms showed no significant improvement.The report of this case deepens the understanding of a complex and commonly misdiagnosed condition,offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.

Objective:To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring′s birth weight and risk of small for gestational age (SGA) infant.Methods:The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1 st September 2016 to 11 th November 2022. A standardized questionnaire was used to collect the mothers′ demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B 12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results:A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) μmol/L, with (8.3±3.7) μmol/L in the preconception subgroup and (7.3±2.4) μmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B 12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight ( β=-2.30, 95% CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight ( β=-7.39, 95% CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring ( RR=1.05, 95% CI 1.01-1.08, P=0.002). Periconceptional vitamin B 12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions:Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed. ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD. MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients. ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P<0.05］. A statistical difference was found in plasma G-CSF level ［63.92（54.60， 89.43）pg/mL vs. 47.80（33.41， 74.66）pg/mL vs. 71.47（61.20， 79.99）pg/mL， H=8.247， P=0.016］ and plasma M-CSF level ［20.05（16.05， 22.23）pg/mL vs. 13.05（11.43， 17.50）pg/mL vs. 18.95（14.59， 22.88）pg/mL， H=7.620， P=0.022］ among retardation group， non-retardation group and healthy control group. The post hoc pairwise comparisons using Bonferroni correction indicated that plasma G-CSF level was lower in non-retardation group compared with healthy control group （adjusted P<0.05）， and plasma M-CSF level was higher in retardation group compared with non-retardation group （adjusted P<0.05）. The retardation factor score in HAMD-17 was positively correlated with plasma M-CSF level in MDD patients （r=0.348， P<0.05）. ConclusionThe prevalence of psychomotor retardation in MDD patients may be related to abnormally elevated plasma M-CSF level. ［Funded by Shanghai "Science and Technology Innovation Action Plan" Project in Medical Innovation Research Field （number， 21Y11905600）； Shanghai "Science and Technology Innovation Action Plan" Project in Natural Science Field （number， 21ZR1455100）； Shanghai Mental Health Center Scientific Research Project （number， 2021-YJ02）］