Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Objective To explore the effect of myotubularin-related protein 6(MTMR6)on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism.Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus(GEO)database,MTMR6 gene was screened out,and Spearman analysis was used to analyze the correlation of MTMR6 and pathway in the Cancer Genome Atlas(TCGA)database.Finally,the interaction between MTMR6 and signaling pathway proteins was analyzed with Genemania database.Then the expression of MTMR6 in human normal liver cell line LO-2 and hepatoma cell lines Huh-7 and HepG2 were measured and compared among the cell lines.Then HepG2 cells was selected as the study object.After MTMR6 gene was knocked down or over-expressed in HepG2 cells,Transwell assay was employed to observe invasion ability,and Western blotting was adopted to detect the expression of MTMR6,PI3K,p-PI3K,AKT,p-AKT,mTOR,p-mTOR MMP-2 and MMP-9.Results The expression of MTMR6 was significantly higher in the hepatocellular carcinoma tissues than the paracancer tissues,and it was in a positive linear correlation with PI3K/AKT/mTOR signaling pathway(P＜0.01),showing interaction with PI3K,AKT and mTOR.The expression level of MTMR6 was significantly higher in the HepG2 cells than the LO-2 and Huh-7 cells(P＜0.01).Over-expression of MTMR6 obviously enhanced invasion ability(P＜0.01),while its knockdown decreased the ability(P＜0.01)in HepG2 cells.Knockdown of MTMR6 gene also resulted in decreased phosphorylation of PI3K,AKT and mTOR,and expression levels of MMP-2 and MMP-9(P＜0.01),while over-expression of MTMR6 promoted the phosphorylation of PI3K,AKT and mTOR,and up-regulated the expression of MMP-2 and MMP-9(P＜0.01).In addition,LY294002(a specific PI3K inhibitor)treatment could block the PI3K/AKT/mTOR pathway and down-regulate the expression of MMP-2 and MMP-9(P＜0.01),but had no effect on MTMR6 expression.Conclusion MTMR6 may promote the invasion of hepatoma cells through activation of PI3K/AKT/mTOR signaling pathway.

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Objective:To analyse the correlation between depression and hip fracture in the middle-aged and elderly population in the Chinese community.Methods:The study data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) database. A total of 16,831 respondents from 12,400 households in the fourth national follow-up data in 2018 were selected as the research sample. The samples were divided into a training set and a test set at a ratio of 7∶3, and the test set data were used for internal validation. For external validation, 2,337 subjects recruited from the Institute of Orthopaedics, the First Affiliated Hospital of Zhejiang Chinese Medical University from 2018 to 2023 were selected as the survey subjects. The Center for Epidemiological Studies Depression Scale (CESD) was used to assess depression. CESD≥16 points were defined as depression, and CESD<16 points were defined as no depression. Binary logistic regression was used to gradually analyze the correlation between depression and hip fracture after adjusting for different covariates.Results:In the training set, statistically significant differences were observed between patients with and without hip fractures in terms of depression prevalence (χ 2=16.310, P<0.001), age (χ 2=9.417, P=0.009), education level ( P<0.001), marital status ( P=0.019), and place of residence ( P=0.035). In the testing set, statistically significant differences were found in depression prevalence (χ 2=10.130, P=0.001), gender (χ 2=4.368, P=0.037), education level ( P=0.013), and smoking history (χ 2=8.804, P=0.012). In the external validation set, significant differences were noted in depression prevalence (χ 2=337.885, P<0.001), age (χ 2=29.475, P<0.001), and smoking history ( P=0.020). After controlling for demographic characteristics, exercise, smoking and drinking history, binary logistic regression showed that the risk of hip fracture in depressed patients was 1.78 times higher in the training set ( OR=1.78, P<0.001), 2.73 times higher in the testing set ( OR=2.73, P=0.002), and 15.21 times higher in the external validation set ( OR=15.21, P<0.001) than that of non-depressed patients, indicating good internal and external validation results. Conclusion:Depression is an independent risk factor for hip fractures among middle-aged and elderly populations in Chinese communities. Early identification and active intervention for depression in this population can help reduce the risk of hip fractures.

Objective:To investigate the effects of three-dimensional computed tomography angiography (3D-CTA)-assisted free medial sural artery perforator flap in repairing foot wounds.Methods:A retrospective observational study was conducted. From May 2018 to August 2021, 18 patients with foot soft tissue defects who met the inclusion criteria were admitted to the Department of Spine and Trauma Orthopedics of the Yidu Central Hospital of Weifang, including 13 males and 5 females, aged 19 to 55 years, with a wound area of 4.0 cm×3.0 cm-9.0 cm×8.0 cm at admission. Before the operation, CT scanner was used to scan the area from the supracondylar femur to the middle segment of the fibula of patients, and the obtained data were extracted into the Mimics16.0 software and analyzed to determine the pre-selected perforator, and then the image data of the pre-selected perforator side were analyzed further, and the body surface projection position of the perforating point of the medial sural artery in the calf region was marked. Based on the above examination, the flap was designed and cut according to the shape and area of the patient's foot tissue defect, and the area of flaps ranged from 5.0 cm×4.0 cm to 10.0 cm×9.0 cm. The donor sites were sutured directly or covered by skin grafting. The type of perforator, the diameters of perforator at the beginning and outlet point, and the location of the outlet point of perforator of the medial sural artery were observed under 3D-CTA examination before operation and compared to see if they were consistent with the observation under intraoperative condition. The survival of the flaps after operation was recorded. During follow-up, the satisfaction of patients with the wound repair effects, the sensory recovery of the recipient flaps, the healing of the donor wound, and whether there were complications affecting limb functions were recorded. Data were statistically analyzed with Kappa consistency test and equivalence test, and the 95% confidence intervals of measurement difference of perforator diameter and outlet point position of perforator were -0.50-0.50 mm and -2.0-2.0 cm, respectively.Results:The types of medial sural artery perforators observed during operation were type Ⅰ in 3 cases, type ⅡA in 6 cases, type ⅡB in 8 cases, and type Ⅲ in 1 case, which was consistent with the results of 3D-CTA before operation (Kappa=1.00, P<0.05). The blood vessel diameter detected by 3D-CTA before operation at the beginning of perforator of medial sural artery was (1.81±0.39) mm, and the blood vessel diameter at the outlet point of the perforator was (0.83±0.21) mm, which were close to the actual intraoperative measurement of (1.83±0.43) and (0.86±0.22) mm, respectively; equivalence test showed that the 95% confidence intervals of the measurement differences of diameter of medial sural artery perforator at beginning and outlet point were -0.18-0.22 and -0.08-0.14 mm, respectively, with both P values <0.05. The preoperative 3D-CTA detected that the perforating position at the deep fascia of the perforator of the medial sural artery, namely the vertical distance with the popliteal fold was (12.2±1.4) cm, and the horizontal distance with the posterior midline was (2.6±0.7) cm, which were respectively close to the actual intraoperative measurement of (12.4±1.4) and (2.6±0.7) cm; equivalence test showed that the 95% confidence intervals of the measurement differences in the vertical distance with the popliteal fold and the horizontal distance with the posterior midline of the outlet point of medial sural artery perforator were -1.06-1.26 and -0.46-0.66 cm, respectively, with both P values <0.05. After surgery, all flaps of 18 patients survived without vascular crisis. After 1 year of follow-up, the satisfaction degree of 16 patients was excellent and 2 patients was good with the wound repair effects, with a satisfaction ratio of 16/18; the sensory recovery of flap was evaluated as S 3 in 11 cases and S 2 in 7 cases; the donor wounds healed well without obvious scar or contracture, with no effect on limb joint functions. Conclusions:The medial sural artery perforator flap achieved good results in repairing foot wound with high degree of patient satisfaction. Preoperative application of 3D-CTA can realize the standardization, systematization, and visualization of artery perforator flap.

OBJECTIVES: We performed an updated meta-analysis to clarify the relationship between the CEBPE rs2239633 polymorphism and the childhood acute lymphoblastic leukemia (CALL) susceptibility. METHODS: All the case-control studies were updated on October 5, 2020, through Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) electronic database. The heterogeneity in the study was tested by the Q test and I RESULTS: A total of 20 case-control studies were selected, including 7014 patients and 16,428 controls. There was no association of CEBPE rs2239633 polymorphism with CALL (CC vs CT + TT: OR = 1.08, 95% CI = 0.94-1.26; CC + CT vs TT: OR = 1.10, 95% CI = 0.94-1.30; C vs T: OR = 1.02, 95% CI = 0.92-1.13). In the subgroup analysis by ethnicity, there is no significant association of this polymorphism and CALL risks among Asian and Caucasian populations in the three genetic models (CC vs CT + TT, CC + CT vs TT, and C vs T). CONCLUSION This meta-analysis found no significant association between the CEBPE rs2239633 polymorphism and susceptibility to CALL.
Adolescent ; CCAAT-Enhancer-Binding Proteins/metabolism* ; Child ; Child, Preschool ; Genetic Predisposition to Disease/genetics* ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*

Objective: To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester. Methods: Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13^{+ 6} weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared. Results: The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus. Conclusions In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

The scar contracture of Achilles tendon in burn patients after operation is easy to cause " foot drop" , which leads to ankle dorsiflexion dysfunction. To solve this problem, the authors designed and made a static progressive ankle foot orthosis. The foot support part and the crus support part of the orthotic device are connected by rivets, and the distal end of the foot support part and the proximal end of the crus support part are pulled by the traction belt on both sides, gradually improving the ankle dorsiflexion function. This static progressive ankle foot orthosis is simple, practical, cost-effective, and worthy of clinical promotion.

Objective To investigate the predictive value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI for microvascular invision (MVI) in hepatocellular carcinoma (HCC). Methods Retrospective analysis of 70 patients confirmed by pathology as HCC who underwent Gd-EOB-DTPA-enhanced MRI within 2 weeks prior to liver partial resection or liver transplantation surgery from January 2015 to May 2018 in Nantong Third People's Hospital. According to the pathological results of the postoperative pathology, MVI was divided into MVI positive group and MVI negative group, and alpha fetoprotein (AFP) was recorded. In Gd-EOB-DTPA-enhanced MRI, qualitative indicators including whether the tumor signal was uniform, peritumoral enhancement, tumor capsule, tumor margin, peritumor hypointensity and presence of fat in the tumor were assessed. Quantitative indicators including tumor diameter and the increase rate of liver-to-muscle ratio(ΔLMR) of post-enhancement arterial phase, portal vein phase, transitional phase and hepatobiliary phase were assessed and recorded. Theχ2 test was used to compare the qualitative parameters of the MVI-negative group and the MVI-positive group, and the Mann-Whitney U test was used to compare the non-normal quantitative parameters. In both inclusion and non-inclusion of peritumor hypointensity cases in the hepatobiliary phase. The multivariate logistic regression analysis was performed to indicate independent variables after univariate analysis. The prediction probability 1 (pre-1) and the prediction probability 2 (pre-2) were obtained, and the two as independent variables. with MVI as the gold standard, using ROC to analyze the diagnostic efficacy of both for HCC MVI, and using Z test to compare the area under the ROC of pre-1 and pre-2. Results There were 27 lesions in 26 cases of MVI-positive group and 50 lesions in 44 cases of MVI-negative group. There was a statistically significant difference between the MVI-negative group and the MVI-positive group in peritumoral enhancement, tumor capsule, tumor margin and peritumor hypointensity in the hepatobiliary phase (P<0.05), and there was no statistically significant difference in gender distribution, tumor signal uniformity and intratumoral fat (P>0.05). There was significant difference in lesion diameter between MVI-negative group and MVI-positive group (P<0.05) while no significant difference in age, AFP value andΔLMR between the two groups (P>0.05). Multivariate logistic regression analysis showed that tumor diameter, non-smooth tumor margin and peritumor hypointensity were independent risks of MVI when peritumor hypointensity was included, the sensitivity and specificity of the combined diagnosis of MVI were 77.8％ and 94.0％;Multivariate logistic regression analysis showed that tumor diameter and non-smooth tumor margin were independent risks of MVI when peritumor hypointensity was not included, the sensitivity and specificity of the combined diagnosis of MVI were 59.3％and 92.0％. The the area under the ROC of pre-1 and pre-2 were 0.900 and 0.816, their difference was statistically significant (P<0.05). Conclusion Gd-EOB-DTPA enhanced MRI can be used to predict HCC MVI preoperatively, especially peritumor hypointensity in hepatobiliary phase is important for the prediction of MVI.