Establishment and application of a prospective follow-up research method for acute infectious diseases in Shanghai community residents / 上海预防医学

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.

Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease： A Cross-sectional Study / 中山大学学报(医学科学版)

ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.

Effect of Atractylodis Macrocephalae Rhizoma on Short-chain Fatty Acids and Intestinal Barrier in Mice with Slow-transit Constipation / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Atractylodis Macrocephalae Rhizoma（AMR） in the treatment of slow-transmission constipation（STC） by observing the effects of AMR on short-chain fatty acids and intestinal barries in STC mice. MethodForty-eight male KM mice were randomly divided into blank group， model group， AMR low-， medium-， high-dose groups（2.5， 5， 10 g·kg-1） and mosapride group（2.5 mg·kg-1）. Except for the blank group， all groups were gavaged with loperamide suspension（5 mg·kg-1） twice daily for 14 d to construct the STC mouse model. At the same time， each drug administration group was given the corresponding drug by gavage for consecutive 14 d， the blank and model groups were gavaged with equal volume of distilled water. The effects of the treatment of AMR on body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice were observed， the pathological changes of mouse colon were observed by hematoxylin-eosin（HE） staining and periodic acid-Schiff（PAS） staining， the levels of gastrin（GAS） and motilin（MTL） in serum were detected by enzyme-linked immunosorbent assay（ELISA）， gas chromatography-mass spectrometry（GC-MS） was used to detect the contents of short-chain fatty acids（SCFAs） in mouse feces， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to determine the mRNA and protein expression levels of zonula occludens-1（ZO-1）， Occludin， and Claudin-1 in the colon of mice. ResultCompared with the blank group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in the model group were significantly decreased（P<0.05， P<0.01）， the arrangement of colonic tissues was disordered， and the number of goblet cells was reduced， the levels of GAS and MTL in serum were significantly decreased（P<0.01）， and the levels of SCFAs in the feces were on a decreasing trend， with the contents of acetic acid， propionic acid， butyric acid， isobutyric acid and valeric acid were significantly decreased（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly decreased（P<0.01）. The above results suggested that STC mouse model was successfully constructed. Compared with the model group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in AMP administration groups all increased significantly（P<0.05， P<0.01）， the mucosal layer of the colonic tissues was structurally intact without obvious damage， and the number of goblet cells increased， serum levels of GAS and MTL were significantly increased（P<0.01）， the contents of SCFAs in the feces were all on a rising trend， with the contents of acetic， propionic， butyric and isobutyric acids rising significantly（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly increased（P<0.05， P<0.01）. ConclusionAMR is able to improve the constipation symptoms in STC mice， and its mechanism may be related to increasing the contents of SCFAs in the intestine as well as promoting the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colon.

Progress on the relationship of aldehyde dehydrogenase 2 with human diseases and its small-molecule activators / 药学实践杂志

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Comparison of Effect of Hirudo， Notoginseng Radix et Rhizoma， and Their Combinations on Renal Fibrosis in Rats with Chronic Renal Failure / 中国实验方剂学杂志

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg-1·d-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg-1·d-1）， Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg-1·d-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

Mechanism of obesity affecting periodontal tissue regeneration and therapeutic strategies / 中华口腔医学杂志

Obesity is an important health problem in our society today, which can lead to the chronic low-grade inflammation state, to be an inducement for many chronic diseases such as hypertension, type 2 diabetes and non-alcoholic fatty liver disease. As a common oral chronic infectious disease, periodontitis is mainly characterized by gingival inflammation, periodontal pocket formation, alveolar bone resorption and tooth mobility. The ultimate goal of periodontitis treatment is to achieve periodontal tissue regeneration in the defect area. As a major risk factor for periodontitis, obesity can alter the periodontal inflammatory microenvironment in multiple ways, affecting the effects of periodontal tissue regeneration ultimately. Therefore, this paper will review the relationship between obesity and periodontal tissue regeneration, mechanism of obesity affecting periodontal tissue regeneration and the therapeutic strategies of periodontal tissue regeneration, providing new ideas for periodontal tissue regeneration treatment in obesity.

Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway / 中华肿瘤杂志

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Arthroscopic treatment of ankle impingement syndrome / 中华创伤杂志(英文版)

Arthroscopic treatment of ankle impingement syndrome (AIS) is a minimally invasive surgical procedure used to address symptoms caused by impingement in the ankle joint. This syndrome occurs when there is abnormal contact between certain bones or soft tissues in the ankle, leading to pain, swelling, or limited range of motion. Traditionally, open surgery was the standard approach for treating AIS. However, with advancements in technology and surgical techniques, arthroscopic treatment has become a preferred method for many patients and surgeons. With improved visualization and precise treatment of the arthroscopy, patients can experience reduced pain and improved functionality, allowing them to return to their daily activities sooner. In this paper, we reviewed the application and clinical efficacy the of arthroscopic approach for treating AIS, hoping to provide a reference for its future promotion.

Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p / 中国骨伤

OBJECTIVE@#To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA.@*METHODS@#Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs.@*RESULTS@#The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs.@*CONCLUSION@#Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

Current Strategies of Surface Modifications to Polyurethane Biomaterials for Vascular Grafts / 中国医学科学杂志(英文版)

As the number of patients suffering from cardiovascular diseases and peripheral vascular diseases rises, the constraints of autologous transplantation remain unavoidable. As a result, artificial vascular grafts must be developed. Adhesion of proteins, platelets and bacteria on implants can result in stenosis, thrombus formation, and postoperative infection, which can be fatal for an implantation. Polyurethane, as a commonly used biomaterial, has been modified in various ways to deal with the adhesions of proteins, platelets, and bacteria and to stimulate endothelium adhesion. In this review, we briefly summarize the mechanisms behind adhesions, overview the current strategies of surface modifications of polyurethane biomaterials used in vascular grafts, and highlight the challenges that need to be addressed in future studies, aiming to gain a more profound understanding of how to develop artificial polyurethane vascular grafts with an enhanced implantation success rate and reduced side effect.

Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor / 中国中药杂志

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Association Between Daily Executive Function and Core Symptoms， Attention Deficit-Hyperactivity Symptoms in Children with Autism Spectrum Disorder / 中山大学学报(医学科学版)

ObjectiveTo explore the association between daily executive function and core symptoms， the symptoms of attention deficit hyperactivity disorder （ADHD） in children with autism spectrum disorder （ASD）， and the moderating effect of theory of mind and other cognitive abilities on this association. MethodsChildren aged 6-12 years with ASD were recruited， and 86 children were identified according to the inclusion and exclusion criteria. Wechsler Intelligence Test for Children， Fourth Edition （WISC-Ⅳ）， Strange Story Test （SST） and Behavior Rating Inventory of Executive Function （BRIEF） were used to evaluate children's cognitive ability. Swanson Nolan and Pelham-Version Ⅳ Scale （SNAP-Ⅳ）， Social Responsiveness Scale （SRS）， and Repetitive Behavior Scale-Revise （RBS-R） were used to assess the severity of ADHD symptoms， social impairment， and repetitive stereotyped behavior. Multiple linear regression was used to explore the association between daily executive function and ADHD symptoms， social impairment， repetitive stereotyped behaviors. ResultsAfter controlling for the score of strange stories， verbal comprehension index （VCI） and other factors， the full scale score and each index of BRIEF were positively correlated with full scale score of SNAP （b = 0.619-0.741， b’ = 0.637-0.755）， SRS （b = 0.928-1.200， b’ = 0.417-0.513） and RBS-R （b = 0.326-0.525， b’ = 0.339-0.520） in children with ASD （P< 0.05）， and the SNAP total score was more strongly correlated with the full scale BRIEF score and each index score （b’ = 0.637-0.755，P< 0.01）. In addition to daily executive function， strange stories score （b = -2.218- -1.839） and age （b = 3.181-4.037） were also the important factors affecting the social function of children with ASD （P< 0.01）. There were no moderating effects of strange stories score and age on the association between BRIEF score and full scale score of SNAP， SRS， and RBS-R（P> 0.05）. ConclusionThe deficits of daily executive function in school-aged ASD children are significantly associated with core symptoms and ADHD symptoms， and the association is independent of other cognitive domains， such as theory of mind and verbal comprehension intelligence quotient.

Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis. MethodThe mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg-1·d-1）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg-1·d-1 and 13.26 g·kg-1·d-1， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg-1·d-1） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining. ResultCompared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （P<0.01）， lowered serum levels of CK-MB， TGF-β1， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， and elevated IL-10 level （P<0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （P<0.01）， and increased CD206 and MDA （P<0.01）. ConclusionFangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

Risk factors and perioperative outcomes of prolonged mechanical ventilation after coronary artery bypass grafting in elderly patients / 中国胸心血管外科临床杂志

@#Objective     To investigate the clinical characteristics, risk factors and perioperative outcome of prolonged mechanical ventilation (PMV) in elderly patients undergoing coronary artery bypass grafting (CABG). Methods     The data of elderly patients receiving CABG in the Nanjing First Hospital from January 2013 to June 2019 were collected. All patients were divided into a control group and a PMV group according to whether ventilation time≥24 h. The clinical characteristics and risk factors of PMV were compared between the two groups. Variables were 1∶1 balanced through propensity score matching (PSM) and perioperative outcomes of two groups was analyzed. Results     Finally 956 patients were collected, including 187 in the PMV group and 769 in the control group. There were 586 males and 370 females aged 70-94 (74.3±3.5) years. Compared with the control group, the PMV group had higher rates of smoking,  preoperative renal impairment, intraoperative blood transfusion and intra-aortic balloon pump (IABP) implantation, worse cardiac function, lower glomerular filtration rate and ejection fraction, larger left atrial diameter, longer cardiopulmonary bypass time and aortic cross-clamping time (P<0.05). There was no statistical difference in other clinical data between the two groups (P>0.05). Binary multivariate logistic regression analysis showed that females, smoking, chronic obstructive pulmonary disease, left ventricular ejection fraction≤56.0%, cardiopulmonary bypass time>106.0 min, IABP implantation and intraoperative blood transfusion were independent risk factors for PMV in elderly patients. After PSM, there were 146 patients in the control group and the PMV group, respectively. The PMV group had longer ICU stay and length of hospital stay and more drainage volume compared with the control group (all P<0.05). There was no statistical difference in perioperative mortality or other complications between the two groups (all P>0.05). Conclusion    There are a lot of factors associated with PMV of the elderly patients undergoing on-pump CABG. In order to establish a complete and formal PMV prediction model, clinicians can make a further step of assessment according to perioperative elements, and improve the prognosis of such patients.

Clinical and epidemiological analysis of 18 cases of Japanese spotted fever in Zigui County / 中华检验医学杂志

Objective:The epidemiological and clinical characteristics of 18 cases of Japanese spotted fever (JSF) in Zigui County were analyzed in order to improve the prevention and treatment of JSF.Methods:This is a case series analysis. The epidemiological and clinical data, laboratory tests and imaging characteristics of 18 JSF cases with median age of 60 years (54, 68) identified by The People′s Hospital of Zigui from April 2021 to August 2022 were collected and analyzed retrospectively.Results:Most (17/18) of the patients were farmers and all had a field exposure history. The patient′s onset was from April to October. Spring and autumn were the seasons with the highest incidence of JSF. The first symptoms of patients were high fever, headache, and fatigue. Of the 18 cases, 15 had a rash and 12 presented an eschar and 3 had neither rash nor eschar. In addition, 10 of 18 cases experienced edema of both lower extremities, and 3 got disturbance of consciousness. Laboratory tests found that 15 patients had abnormal white blood cells and 11 patients had decreased platelets. C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase were elevated in all patients; 13 patients with elevated alanine aminotransferase, 14 patients with elevated aspartate transamination. Kidney damage caused by Rickettsia japonica infection showed by abnormal proteinuria in 11 of the patients. Conclusions:The most common clinical manifestations of JSF are non-specific indications such as high fever, chills, fatigue, headache. The eschar and rash, which are the main features of Rickettsia infection, are not present in all patients, resulting delay of diagnosis or misdiagnosis. Medical workers should be more alert to rickettsial infections in patients with fever of unknown origin, especially in seasons of high incidence of spotted fever. Early diagnosis and correct antibiotic treatment shall be given according to the patient′s clinical manifestations, laboratory results and imaging test to control disease progression.

Progress on the function and mechanism of pigment epithelium derived factor receptors in the occurrence and development of diabetic retinopathy / 中华眼底病杂志

Endogenous pigment epithelium derived factor (PEDF) shows great potential as a drug target for the treatment of diabetes retinopathy (DR) due to its anti-angiogenesis, anti-inflammatory, neuroprotective and neurotrophic effects. PEDF plays a biological role by combining with receptor proteins on cell membrane surface and regulating a variety of signaling pathways. Low density lipoprotein receptor related protein 6 plays a role in inhibiting oxidative stress reaction, inflammatory reaction, and neovascularization of DR. Adipose triglyceride lipase, laminin receptor, plexin domain containing 1 (PLXDC) 1, PLXDC2 and F 1-adenosine triphosphate synthase have the effect of promoting endothelial cell apoptosis, among which PLXDC1 also has neuroprotective effect. By clarifying the receptor that PEDF acts on, exploring the affinity between the receptor and PEDF, the difference in the expression level of each receptor in the process of disease, and the specific function that PEDF plays after binding with specific receptors, we can develop fusion protein drugs for the active domain of high affinity of receptors, have a clearer understanding of the pathogenesis of DR, and take PEDF or PEDF receptor as the target to consolidate the theoretical basis for the development of new therapeutic drugs and strategies for DR.

Extra-anatomic bypass grafting in patients with lower extremity malperfusion due to type A acute aortic dissection / 中华胸心血管外科杂志

Objective:To summarize the efficacy of artificial blood vessel bypass grafting in patients with acute type A aortic dissection (ATAAD) complicated with lower extremity malperfusion.Methods:From January 2004 to January 2021, a total of 896 patients with ATAAD underwent surgical operations in Nanjing First Hospital, Among which 75 patients with lower extremity malperfusion was retrospectively analyzed.Results:There were 61 males and 14 females with mean age (50.9±11.3) years old. The cardiopulmonary bypass time (CPB) was (181.9±27.0) min, the cross-clamp time was (125.7±25.0)min, and the lower body circulatory arrest time was (20.4±3.1) min. Fifty-five patients had total aortic arch replacement and 20 cases had hemi-arch replacement surgery. Lower extremity arterial perfusion was restored in 48 patients after dissection surgery. Twenty-six patients underwent dissection surgery concurrently with extra-anatomic bypass grafting. The main postoperative complications were: acute kidney injury in 9 cases, delayed extubation (≥72 h) in 10, pulmonary infection in 13, tracheotomy in 6, paralysis in 1, stroke in 2 and lower limb amputation in 3. ICU stay time was (5.8±4.5) days, in-hospital time was (21.4±13.8) days. Nine patients (12%) died in the whole group: pulmonary infection, respiratory failure in 2 cases, multiple organ failure in 3 cases, iliac artery rupture in 1 case, intestinal necrosis in 1 case, severe cerebral infarction in 1 case, and giving-up in 1 case. A total of 66 patients (88%) were successfully discharged. The follow-up time was (55.8±33.4) months. The results of survival analysis showed that the 5-year survival rate was (96.7±4.2)%, and the 10-year survival rate was (56.4±16.3)%.Conclusion:Extra-anatomic bypass grafting is a feasible method to solve ATAAD complicated with lower extremity malperfusion. It is simple and easy to operate, and the long-term effect is satisfactory.