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Due to sudden loss of cerebral blood circulation, acute ischemic stroke (IS) causes neuronal energy attenuation or even exhaustion by mitochondrial dysfunction resulting in aggravation of neurological injury. In this study, we investigated if Notoginsenoside R1 ameliorated cerebral energy metabolism by limiting neuronal mitochondrial dysfunction in acute IS. Male Sprague-Dawley rats (260-280 g) were selected and performed by permanent middle cerebral artery occlusion model. In vitro, the oxygen glucose deprivation (OGD) model of Neuro2a (N2a) cells was established. We found Notoginsenoside R1 treatment reduced rats' cerebral infarct volume and neurological deficits, with increased Adenosine triphosphate (ATP) level together with upregulated expression of glucose transporter 1/3, monocarboxylate transporter 1 and citrate synthase in brain peri-ischemic tissue. In vitro, OGD-induced N2a cell death was inhibited, cell mitochondrial morphology was improved. Mitochondrial amount, mitochondrial membrane potential, and mitochondrial DNA copy number were increased by Notoginsenoside R1 administration. Furthermore, mitochondrial energy metabolism-related mRNA array found Atp12a and Atp6v1g3 gene expression were upregulated more than twofold, which were also verified in rat ischemic tissue by quantitative polymerase chain reaction (qPCR) assay. Therefore, Notoginsenoside R1 administration increases cerebral glucose and lactate transportation and ATP levels, ameliorates neuronal mitochondrial function after IS. Notoginsenoside R1 may be a novel protective agent for neuronal mitochondria poststroke.

Context Maternal thyroid hormone trajectories are a better predictor of offspring’s neurodevelopment than hormone levels in single trimester of pregnancy. Programming effect of uterine hormonal environment on offspring’s health is usually sex-specific. Objective To examine the sex-specific effect of thyroid hormone trajectories on preschoolers’ behavioral development. Design Based on Ma’ anshan Birth Cohort in China, pregnant women were recruited at their first antenatal checkup from May 2013 to September 2014. Setting Ma’ anshan Maternal and Child Health Hospital in China. Patients or Other Participants 1860 mother-child pairs were included in the analysis. Children were followed up at age of 4. Main Outcome Measures Maternal thyroid hormones [thyroid-stimulating hormone (TSH), free thyroxine (FT4)] and thyroid peroxidase antibody in the first, second, and third trimesters of pregnancy were retrospectively assayed. Preschoolers’ behavioral development was assessed by Achenbach Child Behavior Checklist/1.5~5. Results Maternal TSH and FT4 levels were respectively fitted into high, moderate, and low trajectories. In boys, maternal high TSH trajectory was related to withdrawn [odds ratio (OR) = 2.01, 95% CI: 1.16, 3.50) and externalizing problems (OR = 2.69, 95% CI: 1.22, 5.92), and moderate TSH trajectory was associated with aggressive behavior (OR = 3.76, 95% CI: 1.16, 12.23). Maternal high FT4 trajectory was associated with anxious/depressed (OR = 2.22, 95% CI: 1.08, 4.56) and total problems (OR = 1.74, 95% CI: 1.13, 2.66), and low FT4 trajectory was associated with aggressive behavior (OR = 4.17, 95% CI: 1.22, 14.24). Conclusions Maternal thyroid hormone trajectories impact preschool boys’ behavioral development.

Gradual distraction with an external fixator is a widely used treatment for severe postburn ankle contracture (SPAC). However, application of external fixators is complex, and conventional two-dimensional (2D) imaging-based surgical planning is not particularly helpful due to a lack of spatial geometry. The purpose of this study was to evaluate the surgical planning process for this procedure with patient-specific three-dimension-printed models (3DPMs). In this study, patients coming from two centers were divided into two cohorts (3DPM group vs. control group) depending on whether a 3DPM was used for preoperative surgical planning. Operation duration, improvement in metatarsal-tibial angle (MTA), range of motion (ROM), the American Orthopedic Foot and Ankle Society (AOFAS) scores, complications, and patient-reported satisfaction were compared between two groups. The 3DPM group had significantly shorter operation duration than the control group ((2.0±0.3) h vs. (3.2± 0.3) h, P

Objective This research was performed to investigate the correlation between acute kidney injury (AKI) and systemic immune-inflammation index (SII) in severe acute pancreatitis (SAP) patients. Methods The study included 218 SAP patients from Chongqing Jiangjin Center Hospital during January 2016 to October 2020. The SII was defined as platelet × neutrophil/lymphocyte ratio. After univariate analysis, logistic regression analysis was used for analyzing independent risk factors of AKI in SAP patients. Receiver operating characteristic (ROC) curve was used for analyzing the prognostic value of the SII. Results AKI occurred in 74 cases and its incidence rate was 33.9%. The median SII value of AKI patients was higher than that of patients without AKI. After multivariate analysis, SII, age, triglyceride (TG), neutrophil ratio (NEU-R), C-reactive protein (CRP), aspartate aminotransferase (AST), and serum albumin (ALB) were independent predictors of AKI. Serum ALB was an independent protective factor. The optimum threshold truncation value of SII was 2880.1*10^9/L. Compared with other inflammatory factors, SII had a better prediction efficiency. Conclusion The SII, TG, NEU-R, CRP, and ALB were significant independent predictors of AKI in SAP patients. Serum TG, NEU-R, CRP, and SII were risk factors. Serum ALB was a protective factor. The SII may be a novel, simple, and strong marker for the accurate early prediction of AKI in SAP patients.

Men who have sex with men (MSM) are a priority population for preexposure prophylaxis (PrEP) for HIV prevention. We summarized the surveillance data from the studies of MSM taking PrEP versus before taking PrEP to investigate the possible increased risk of sexually transmitted infections (STIs).Two researchers independently searched 5 databases from January 2012 to April 2022 to identify relevant studies reporting the incidence density of syphilis, gonorrhea, and chlamydia infection. Subgroup analyses based on the type and location of research were conducted. The publication bias was detected by Egger's publication bias plot.Twenty studies met the inclusion criteria for the meta-analysis. The pooled estimate of incidence density of syphilis was 9.53 per 100 person-years (PY), whereas 36.48 per 100 PY for chlamydial infection and 34.79 per 100 PY for gonorrhea, higher than the MSM before taking PrEP. The results of the subgroup analysis showed that the incidence density tended to be lower in prospective studies than in retrospective studies and lower in North American studies than in other regions' studies.The high incidence of STIs in the MSM taking PrEP needs to be increasingly appreciated, and more effective prevention method for STIs is valuable among MSM alongside HIV prevention uptake.

biBackground:/i/bEpidemiological and experimental studies suggest that thyroid peroxidase antibody (TPOAb)- and thyroglobulin antibody (TGAb)-positive exposure during gestation may contribute to offspring's adverse neural development. However, limited knowledge is available on the association between joint exposure on TPOAb and TGAb and children's emotional and behavioral development. Furthermore, the sex-specific effect on the developmental process of preschoolers' emotions and behaviors is unknown. The present research intends to examine the sex-specific effect of TPOAb- and TGAb-positive exposure in gestation on the developmental process of preschoolers' emotions and behaviors.biMethods:/i/bA total of 2455 mother-child pairs were included from the Ma'anshan Birth Cohort study. The serum TPOAb and TGAb of pregnant women was measured retrospectively by electrochemical immunoassay during the follow-up period. Preschoolers' emotional and behavioral development was assessed by a child behavior checklist 1.5-5. Growth mixture modeling was adopted to fit thyroid antibody (TAb) trajectories. Poisson regression models were used, stratifying by sex, to examine the association between TAb trajectories, as well as four categories of maternal TAb exposure and preschoolers' emotional and behavioral problems.biResults:/i/bBoys born to mothers with TPOAb positivity in the first, second, and third trimesters of pregnancy had an increased risk of autism spectrum problems after adjusting for confounders, with relative risk (RR) [confidence interval, CI] of 2.01 [1.24-3.27], 2.15 [1.08-4.26], and 2.13 [1.20-3.79], respectively. Maternal TGAb positivity and TPOAb negativity in the first trimester were associated with a high risk of attention-deficit/hyperactivity problems in boys (RR = 1.74 [CI 1.01-2.99]). The prevalence of depressive problems in girls was 33.3% after exposure to TPOAb alone in the third trimester of pregnancy. Exposure to TPOAb alone in the third trimester of pregnancy was associated with an increased risk of depressive problems in girls (RR = 1.78 [CI 1.09-2.90]).biConclusions:/i/bMaternal TPOAb positivity in all three trimesters was associated with the risk of autism spectrum problems in boys. Isolated maternal TGAb positivity in the first trimester was associated with attention-deficit/hyperactivity problems in boys, whereas isolated maternal TPOAb positivity in the third trimester was associated with depressive problems in girls.

Objective In the present study, we explored the clinical effect of midazolam as an adjuvant analgesic and tranquilizer after brachial plexus block anesthesia with the aid of imaging guidance. Methods We selected 106 patients who had undergone elective unilateral upper extremity surgery from January 2017 to December 2019 and randomly divided them into groups A and B, with 53 cases in each group. All the patients had undergone brachial plexus block anesthesia. Group A received imidazole-assisted sedation, and group B received fentanyl plus midazolam-assisted sedation. Under ultrasound-guided intermuscular sulcus brachial plexus block, we observed and recorded the ultrasound anatomical images before injection, including the distance from the lower edge of the upper, middle, and lower trunk of the forearm brachial plexus to the skin. We also recorded the anesthesia and operation times, effects of the anesthetic block, and incidence of adverse reactions. Results The distance from the lower edge of each nerve trunk to the skin averaged 1.002 cm for the upper stem, 1.598 cm for the middle stem, and 2.26 cm for the lower stem. The average anesthesia procedure time was 3 minutes, 56 seconds and was within 3–5 minutes for 92% of the procedures. The anesthesia effect was excellent, good, and poor in 81%, 11%, and 6%, respectively, and ineffective for 2% and effective for 92%. Conclusions The ultrasound-guided inferior intermuscular sulcus approach for brachial plexus block is suitable for unilateral upper extremity radial hand surgery. For surgery involving the upper extremity ulnar hand side, a larger dose (concentration) of local anesthetic should be used within a safe range and/or an additional ulnar nerve block might be necessary. Midazolam adjuvant medication can have a good sedative and amnestic effect in brachial plexus block anesthesia, helping to reduce pain and inhibit the increase in stress levels.

To explore the effectiveness of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction in the treatment of head titanium mesh exposure complicated with soft tissue infection.Between January 2015 and December 2021, 13 patients with head titanium mesh exposure complicated with soft tissue infection were admitted. There were 9 males and 4 females with a mean age of 42.9 years (range, 23-64 years). The duration of titanium mesh exposure was 22-609 days (median, 102 days). The wound site located at the frontal part in 3 cases, the parietal part in 1 case, the occipital part in 2 cases, the frontal-parietal part in 1 case, the temporal-parietal part in 4 cases, and the frontotemporal part in 2 cases. The titanium mesh had been taken out in 5 patients before admission, leaving skull defect and shape collapse, with signs of infection. The bacterial culture was positive in 7 cases and negative in 6 cases. The imaging examination revealed that the size of the skull defect ranged from 6 cm×5 cm to 21 cm×17 cm and the scalp defect ranged from 1 cm×1 cm to 15 cm×10 cm. The soft tissue infection did not reach dura in 5 cases, reached dura in 6 cases, and reached frontal sinus in 2 cases. The two-stage surgical protocol was used in all patients. In the first-stage operation, the latissimus dorsi myocutaneous flap was designed to repair the skull and scalp defects after removing the titanium mesh and thorough debridement. The size of muscle flap ranged from 13.5 cm×4.0 cm to 21.0 cm×17.0 cm, and the skin flap ranged from 7.0 cm×4.0 cm to 15.0 cm×10.0 cm. After the flap survived and stabilized, the second-stage operation was performed. The titanium mesh was implanted to reconstruct the skull contour. The size of titanium mesh ranged from 7.0 cm×6.0 cm to 21.5 cm×17.5 cm. The interval between the first- and second-stage operations was 3.7-17.8 months, with an average of 11.4 months. The survival of the skin flap, the appearance of the head, and the presence of re-exposed titanium mesh and infection were observed after operation.At the first-stage operation, venous embolism occurred in 1 case, and no obvious abnormality was observed after treatment. All the flaps survived and the incisions healed by first intention. Besides, the incisions of the second-stage operation healed by first intention. All patients were followed up 1-96 months (median, 14 months). During follow-up, no exposure to titanium mesh, infection, or other complications occurred. The appearance satisfaction rate of the patients was 92.31% (11/13). There was no significant difference in the skull contour between the affected side and the healthy side in all patients.For the head titanium mesh exposure with soft tissue infection, the application of two-stage operation on free latissimus dorsi myocutaneous flap transplantation and skull contour reconstruction can reduce the risks of implant exposure and infection again by increasing the thickness of the scalp and blood supply, filling the wound cavity, and obtain good effectiveness.探讨分阶段游离背阔肌皮瓣移植及颅骨轮廓重建治疗头部钛网外露合并软组织感染的疗效。.2015年1月—2021年12月，收治13例头部钛网外露合并软组织感染患者。男9例，女4例；年龄23～64岁，平均42.9岁。钛网暴露时间22～609 d，中位时间102 d。创面部位：额部3例，顶部1例，枕部2例，额顶部1例，颞顶部4例，额颞部2例。其中5例该次入院前钛网已取出，遗留颅骨缺损和外形塌陷，存在感染征象。细菌培养阳性7例，阴性6例。影像学检查示颅骨缺损范围为6 cm×5 cm～21 cm×17 cm，头皮缺损范围为1 cm×1 cm～15 cm×10 cm；软组织感染深度：未侵及硬脑膜5例，侵及硬脑膜6例，侵及额窦2例。采用分阶段手术方案，第1阶段取出钛网、彻底清创后，切取背阔肌皮瓣修复颅骨及头皮缺损。背阔肌皮瓣切取范围：肌瓣13.5 cm×4.0 cm～21.0 cm×17.0 cm，皮瓣7.0 cm×4.0 cm～15.0 cm×10.0 cm。待皮瓣成活稳定后行第2阶段手术，再次植入钛网，重建颅骨轮廓；钛网范围为7.0 cm×6.0 cm～21.5 cm×17.5 cm。两次手术间隔时间3.7～17.8个月，平均11.4个月。术后观察皮瓣成活、头部外观，有无钛网再次外露和感染等情况发生。.第1阶段术后1例出现皮瓣静脉栓塞，经处理后未见明显异常；背阔肌皮瓣全部成活，供受区创面均Ⅰ期愈合。第2阶段术后切口均Ⅰ期愈合。13例患者均获随访，随访时间1～96个月，中位时间14个月。随访期间无再次钛网外露、感染等情况发生。末次随访时，患者外观主观满意率为92.31%（11/13）。所有患者创区颅骨轮廓与健侧无明显差异。.对于头部钛网外露合并软组织感染，分阶段游离背阔肌皮瓣移植及颅骨轮廓重建方案通过增加头皮厚度及血供、填塞死腔，减少了钛网再次暴露和二次感染风险，临床疗效确切。.

Background: Previous studies suggested blood pressure variability (BPV) might help reveal interactions between blood pressure fluctuation and white matter lesions, and the impact of elevated BPV on white matter hyperintensity (WMH) or cerebral arterial dilation is unclear. Methods: This retrospective observational study involved 2634 stroke-free individuals (68.6±11.1 years, 50.3% female), who underwent magnetic resonance imaging and magnetic resonance angiography scans, from a single center in Shanghai, China. Measurements for variability of blood pressure were made based on 7 days blood pressure recordings. WMHs were quantified from T2-FLAIR images and further classified as periventricular WMH or deep WMH. M1 segment of middle cerebral artery dilation was assessed from magnetic resonance angiography images. General linear model was used to examine the associations. Results: Both increased systolic and diastolic BPV were associated with increased WMH volume (systolic: β =0.02 [95% CI, 0.004–0.03], P =0.01; diastolic: β =0.05 [95% CI, 0.03–0.08], P β =0.02 [95% CI, 0.005–0.04], P =0.01; diastolic: β =0.06 [95% CI, 0.04–0.09], P β =0.11 [95% CI, 0.06–0.17], P β =0.17 [95% CI, 0.11–0.23], P Conclusions: Increased BPV might be one of the pathophysiological phenomena involving in the small vessel disease independent of hypertension. Increased BPV might independently contribute to intracranial arterial dilation. Management of BPV might be a target to preserve cerebrovascular wellness.

Objectives Due to the impact of COVID‐19 epidemic, face‐to‐face follow‐up treatments for patients with chronic pain and implanted spinal cord stimulation (SCS) devices are forced to be delayed or stopped. This has led to more follow ups being done remotely. Meanwhile, with the development of 4G/5G networks, smartphones, and novel devices, remote programming has become possible. Here, we investigated the demand and utility of remote follow‐ups including remote programming for SCS for patients with chronic pain. Materials and Methods A questionnaire including questions on demographic characteristics, pain history, postimplantation life quality, standard follow‐up experience, remote follow‐up, and remote programming experience was sent to patients diagnosed as chronic intractable pain and treated with SCS during January 2019 to January 2020. Results A total of 64 participants completed the questionnaire. About 70% of participants expressed demands for remote follow‐ups due to the inconvenience, high costs, and time consumption of traditional follow‐up visits. Nearly 97% of participants have attempted remote follow‐ups, and about 81% of participants have further tried remote programming. Approximately, 96% of them recognized the benefits. Conclusions The remote programming was in high demand among participants. Most of the participants have tried remote follow‐ups or even remote programming. The remote programming appeared to be more efficient, economic and were widely recognized among participants.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with working memory (WM) in many studies, but the results have not been consistent. One plausible explanation is sex-specific effects of this polymorphism as reported in several studies. The current study aimed to explore the sex-specific effects of the COMT Val158Met polymorphism on WM-related brain function in an elderly sample. We found that Val homozygotes outperformed Met allele carriers on the backward digit span subtest for both males and females. The triangular part of the left inferior frontal gyrus and the left inferior temporal gyrus exhibited higher activation in Met allele carriers compared with Val homozygotes during the n-back task, while the background functional connectivity (bFC) between the left angular gyrus (ANG) and the right ANG was enhanced in Val homozygotes as compared to Met allele carriers. Finally, the associations between brain activation, bFC (among various regions), and WM performance were identified only in specific genotype groups of the female participants. These findings provide new insights into the role of COMT Val158Met gene polymorphism in brain function, particularly its female-specific nature.

The study will be a nationwide cross-sectional survey to estimate the prevalence of chlamydial infections among MSM who meet the inclusion criteria over a period of 6 months (May-October 2022). A total of 2429 participants will be recruited from the venues where MSM most often seek sex partners in 14 cities of the 7 geographical regions in China. A mobile phone app-based anonymous self-administered questionnaire will be used to collect sociodemographic and behavioural data, and specimens of urine, anorectal and pharyngeal swabs will be collected for identifying the infections of CT andChiCTR2100052869.

Childhood trauma (CT) is a well‐established risk factor for major depressive disorder (MDD). However, the underlying mechanism linking CT and MDD remains not fully understood. The present study tested the hypothesis that CT have effects on specific types of anhedonia in depression via reward system. To do so, we evaluated different aspects of anhedonia and resting‐state functional connectivity (FC) in reward system among 66 patients with MDD (44 with moderate‐to‐severe and 22 with no or low CT), and 57 healthy controls (HC; 23 with moderate‐to‐severe and 34 with no or low CT). Results showed that MDD patients with moderate‐to‐severe CT suffered more severe state anhedonic depression than patients with no or low level of CT. Individuals with moderate‐to‐severe CT, irrespective of MDD diagnosis, had elevated physical, social and anticipatory but not consummatory trait anhedonia, and demonstrated decreased left nucleus accumbens (NAcc)‐right orbital frontal cortex (OFC) and left ventral caudate‐left OFC connectivity compared to those with no or low exposure. Left NAcc‐right OFC connectivity mediated relationship between CT and state anhedonia in MDD. The total altered ventral striatum (VS)‐OFC connectivity mediated links between CT and physical trait anhedonia in HC. These findings highlight specific types of anhedonia and the core reward system as targets of CT. Blunted hedonic responses via decreased coupling within core reward system may be involved in the mechanism of depression following CT. Implications for clinical interventions are also discussed.

Changes in cerebral glucose metabolism after subdural hematoma have been rarely reported. We present a case with acute subdural hematoma detected unexpectedly on FDG PET/CT. Focal intense FDG uptake in the cerebral parenchyma beneath the subdural hematoma was seen on PET. The density of the cerebral parenchyma was normal on CT. The patient received conservative management. He recovered without any complication. This case indicates that familiarity with the changes in cerebral glucose metabolism on PET after subdural hematoma may be helpful for optimal patient care.

BackgroundChlamydia trachomatis(CT) infection is one of the most pervasive sexually transmitted infections and has high prevalence in urogenital and extra-urogenital sites among men who have sex with men (MSM). This study investigated anatomical site-specific prevalence and genotypes of CT among MSM recruited from three geographic areas in China.MethodsWe collected urine specimens and anorectal, pharyngeal swab specimens from 379 MSM. CT infection was identified using polymerase chain reaction and CT genotyping was determined by sequences of the ompA gene.ResultsThe results indicated that the overall prevalence of CT infection was 18.2% (95% confidence intervals [CIs], 13.9–22.5%) and significantly different between the cities (p = 0.048). The infection was most common at the anorectal site (15.6, 95%CIs 11.6–19.5%) followed by urethral (3.2, 95%CIs 1.4–5.0%) and oropharyngeal sites (1.6, 95%CIs 0.3–2.9%). Genotypes D and G were the most common CT strains in this population but genotype D was significantly predominated in Nanjing while genotype G was in Wuhan. No genotype related to lymphogranuloma venereum was found. CT infection was significantly related to the infection ofNeisseria gonorrhoeae(adjusted odds ratio [aOR] 14.27, 95%CIs 6.02–33.83,p p = 0.03).ConclusionThe high CT infection prevalence, particularly in the anorectal site, among MSM suggests the necessity to development an integrated CT screening and treatment program specifically focusing on this high-risk population. Surveillance of CT infections should be improved by including both infection and genotype based surveys into the current surveillance programs in China.

Background Although external circular frame (ECF) has been widely used for the correction of knee and ankle deformities, few studies reported the use of ECF for the treatment of severe postburn elbow contracture and stiffness (SPECS). The purpose of this retrospective study was to investigate the effectiveness and safety of the distraction using ECF in treating SPECS. Methods After institutional review board approval, we implemented a retrospective single-center case series study composed of consecutive patients treated for SPECS at Chinese PLA General Hospital between January 2010 and January 2018. After scar release and skin grafting, distraction with ECF was performed for 4 to 6 weeks, and the frame was retained for 2 more weeks before removal. Four weeks of splinting and at least 1 year of rehabilitation were recommended. Patient demographics, active and passive range of motion (ROM) of the elbow at different time points (preoperative, postdistraction, and final follow-up), and complications were collected from the electronic medical record. The primary outcome was the long-term improvement of the ROM. Other outcomes included complications and recurrence. Results The ECF was used to treat SPECS in 6 patients (3 males and 3 females, average age of 11.7 ± 2.6 years). Scar release and distraction with ECF significantly increased both active (from 3° preoperative to 38.7° postdistraction) and passive (from 3.5° preoperative to 48.3° postdistraction) ROM over an average distraction duration of 5.2 weeks. The long-term improvement of active and passive ROM was 38° ± 13.4° and 46° ± 14.7°, respectively, over a median follow-up of 4.1 years. Pin-tract infection occurred in 2 patients and were treated with local wound care and oral antibiotics. A tendon readhesion developed in 1 of the 6 patients because of noncompliance with splinting and physiotherapy, and was treated with revision surgery. Conclusions The 3C strategy (i.e., contracture release, coverage of the defect with skin grafting, and correction of articular angle with gradual distraction using the ECF) is able to increase the ROM with minor complications. We recommend distraction with ECF as part of the treatment arsenal, particularly for severe contractures in which 1-stage correction is unfeasible because of considerable soft tissue shortening.

Jia Ke,1,* Meng-Ting Li,1,* Ya-Jing Huo,1 Yan-Qiong Cheng,2 Shu-Fen Guo,1 Yang Wu,1 Lei Zhang,3 Jianpeng Ma,4 Ai-Jun Liu,2 Yan Han1 1Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Department of Vascular Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ai-Jun LiuDepartment of Pharmacology, School of Pharmacy, Second Military Medical University, 800 Xiangyin Road, Yangpu, Shanghai, 200433, People’s Republic of ChinaEmail mrliuaijun@163.comYan HanDepartment of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou, Shanghai, 200437, People’s Republic of ChinaTel +86 21 51322043Email hanyan.2006@aliyun.comPurpose: We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models.Methods: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5ʹ-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways.Results: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR.Conclusion: Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.Keywords: Ginkgo biloba, aspirin, antiplatelet, synergistic effect, Chinese herb, arachidonic acid

Aim This study investigated the roles of bone morphogenetic protein-4 (BMP4) and ROS in diabetic endothelial dysfunction and explored whether Salvianolic acid B (Sal B) improved endothelial function by affecting BMP4-ROS in diabetic mice. Main methods db/db mice were orally administrated with Sal B (10 mg/kg/day) for one week while db/m + mice were injected with adenoviral vectors delivering BMP4 (3 × 108 pfu) and then received one week-Sal B treatment. ROS levels were assayed by DHE staining. Protein expression and phosphorylation were evaluated by Western blot. Aortic rings were suspended in myograph for force measurement. Flow-mediated dilatations in the second-order mesenteric arteries were determined by pressure myograph. Key findings We first revealed the existence of a BMP4-ROS cycle in db/db mice, which stimulated p38 MAPK/JNK/caspase 3 and thus participated in endothelial dysfunction. One week-treatment or 24 h-incubation with Sal B disrupted the cycle, suppressed p38 MAPK/JNK/caspase 3 cascade, and improved endothelium-dependent relaxations (EDRs) in db/db mouse aortas. Importantly, in vivo Sal B treatment also improved flow-mediated dilatation in db/db mouse second order mesenteric arteries. Furthermore, in vivo BMP4 overexpression induced oxidative stress, stimulated p38 MAPK/JNK/caspase 3, and impaired EDRs in db/m + mouse aortas, which were all reversed by Sal B. Significance The present study demonstrates that Sal B ameliorates endothelial dysfunction through breaking the BMP4-ROS cycle and subsequently inhibiting p38 MAPK/JNK/caspase 3 in diabetic mice and provides evidence for the additional new mechanism underlying the benefit of Sal B against diabetic vasculopathy.

Background There is still a certain gap between the effective implementation and requirements of sepsis bundle. Our aim is to establish the clinical nursing pathway of the cluster treatment of septic shock in the Intensive Care Unit and promote effective implementation of the cluster treatment of septic shock. Methods By means of evidence-based method, quality control index requirements and on-site investigation, the implementation process of clinical nursing pathway of the cluster treatment within 6 h of diagnosis of septic shock was established. Results After the implementation of clinical nursing pathway, the completion rate of septic shock cluster treatment was 81.4% (66.4%) in 1 h, 89.4% (77.0%) in 3 h, 95.5% (82.3%) in 6 h (P Conclusions The clinical nursing pathway of septic shock cluster treatment is guided by evidence-based nursing, which emphasizes standardization and standardization of septic shock cluster treatment nursing under the guidance of the guideline, and can promote the effective implementation of septic shock cluster treatment, significantly improve efficiency of septic shock treatment and the quality of medical care.

The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), which are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The alloimmune rejection postvascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose-derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but their therapeutic results in the VCA are unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, the genes of CCR7–GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multidifferentiation and immunoregulatory abilities, but it gained the migration capacity elicited by secondary lymphoid organ chemokine (SCL) (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetedly relocated in the T-cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had a rare effect on the allografted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts’ survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the downregulated rejection response. Moreover, the proteomic examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation, and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensifies their in vivo immunomodulatory effect in the VCA model for the first time. We believe this SLO-targeting strategy may improve the clinical therapeutic efficacy of hASC for allogeneic and autogenic immune disease. Stem Cells 2019;37:1581–1594

BACKGROUND Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

The mechanism of knee osteoarthritis (OA) is still not clearly elucidated. SMAD3 gene polymorphisms are considered to play a vital role in OA pathogenesis. We thus investigated the relationship of SMAD3 rs1065080 gene polymorphism and susceptibility to knee osteoarthritis in a Chinese Han population. A total of 237 patients and 142 healthy control participants were enrolled in a case-control study. DNA was extracted from peripheral blood samples and genotyped by using the Mass-ARRAY method. Our results revealed that there was a significant difference between patients and healthy controls in the genotype of A and G (p = 0.019); those with a GG genotype had a significant increase in OA risk (OR 2.881, 95% CI 1.993-7.353, p = 0.025). In addition, logistic regression analysis showed that the recessive genetic model decreased OA morbidity (OR 0.648, 95% CI 0.416-0.911, p = 0.046). In conclusion, the GG genotype of rs1065080 was associated with a higher risk of OA and the recessive genetic model decreased the risk of OA.

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling. NEW & NOTEWORTHY Prolonged exercise may impact some people leading to pathological cardiac hypertrophy. This study using an animal model of fatigue-induced cardiac hypertrophy provides evidence showing the potential of QiShenYiQi Pills, a novel traditional Chinese medicine, to prevent the cardiac adaptive hypertrophy from development to pathological hypertrophy and demonstrates that this effect is correlated with its capacity for regulating energy metabolism through interacting with insulin-like growth factor-1 receptor.

Supplemental Digital Content is available in the text, Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are known to participate in regulating mitochondrial function. However, whether Total Salvianolic Acid Injection (TSI) protects against myocardial ischemia/reperfusion (I/R) injury through regulating Sirt1, Sirt3, and mitochondrial respiratory chain complexes is unclear. The aim of this study was to explore the effects of TSI on I/R-induced myocardial injury and the underlying mechanism. Male Sprague–Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 90 min reperfusion with or without TSI treatment (8 mg/kg/h). The results demonstrated that TSI attenuated I/R-induced myocardial injury by the reduced infarct size, recovery of myocardial blood flow, and decreased cardiac apoptosis. Moreover, TSI protected heart from oxidative insults, such as elevation of myeloperoxidase, malondialdehyde, hydrogen peroxide, ROS, as well as attenuated I/R-elicited downregulation of Sirt1, Sirt3, NADH dehydrogenase [ubiquinone] 1 alpha subcomplex 10 (NDUFA10), succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA), and restoring mitochondrial respiratory chain complexes activity. The in vitro study in H9c2 cells using siRNA transfection further confirmed the critical role of Sirt1 and Sirt3 in the effect of TSI on the expression of NDUFA10 and SDHA. These results demonstrated that TSI attenuated I/R-induced myocardial injury via inhibition of oxidative stress, which was related to the activation of NDUFA10 and SDHA through the upregulation of Sirt1 and Sirt3.

Necroptosis refers to a programmed form of necrosis, which involves the receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). In this study, to investigate the role of necroptosis in the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), we retrospectively analyzed 122 patients with ACHBLF, 131 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs). Using quantitative real-time polymerase chain reaction (RT-qPCR), we measured RIPK3 mRNA levels in peripheral blood mononuclear cells (PBMCs). ELISA was performed to measure the serum levels of MLKL, TNF-α and caspase-8. We found that RIPK3 mRNA levels were significantly higher in patients with ACHBLF than those with CHB or HCs. RIPK3 mRNA levels in patients with ACHBLF were positively correlated with serum levels of TNF-α or MLKL and negatively correlated with caspase-8 levels. Univariate and multivariate analysis revealed that RIPK3 mRNA level was predictive of 3-month mortality of ACHBLF. The area under receiver operating characteristic curve (AUC) of RIPK3 mRNA levels was 0.810 (95% CI: 0.729-0.876), which was higher than that of MELD scores (0.766, 95% CI: 0.681-0.838). The optimal cut-off point of 8.81 was determined for RIPK3 mRNA levels, which showed a sensitivity of 80.7% and a negative predictive value of 80.4%. These results indicate that elevated RIPK3 mRNA levels in PBMCs are associated with poor prognosis of ACHBLF. We thus propose that necroptosis may play an important role in pathogenesis of ACHBLF.

Investigating the molecular mechanisms of myocardial infarction (MI) and subsequent heart failure have gained considerable attention worldwide. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been previously demonstrated to regulate the proliferation and metastasis of several tumors. However, little is known about the effects of MALAT1 in MI and in regulating the cell date after MI. In our study, first, it was shown that the expression levels of MALAT1 were increased in the MI samples compared with normal tissues using quantitative reverse-transcription polymerase chain reaction. Then, MALAT1 knockdown could significantly decrease the cell viability and increase the apoptotic rates in isoproterenol (ISO)-treated H9C2 cells. In addition, we screened the possible target and found that miR-558 is its direct target using dual luciferase reporter assay, indicating that MALAT1 functioned as decoys sponging miR-558. Transfection of miR-558 mimic decreased the cell viability and enhanced the apoptosis. Furthermore, we revealed that miR-558 could downregulate ULK1 expression and suppressed ISO-induced protective autophagy. Activation of MALAT1/miR-558/ULK1 pathway protected H9C2 cells from ISO-induced mitochondria-dependent apoptosis. Finally, we used MALAT1-knockout mice to further demonstrated that MALAT1 protected cardiomyocytes from apoptosis and partially improved the cardiac functions upon ISO treatment. In conclusion, we elucidated that lncRNA MALAT1 protected cardiomyocytes from ISO-induced apoptosis by sponging miR-558 thus promoting ULK1-dependent autophagy. Targeting lncRNA MALAT1 might become a potential strategy in protecting cardiomyocytes during MI.

The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury, which represents a key issue in clinical transplantation determining early outcome and long-term graft survival. A solution is needed to deal with this insult. This study was undertaken to explore the effect of Caffeic acid (CA), a naturally occurring antioxidant, on I/R injury of grafted liver and the mechanisms involved. Male Sprague-Dawley rats underwent orthotopic liver transplantation (LT) in the absence or presence of CA administration. In vitro, HL7702 cells were subjected to hypoxia/reoxygenation. LT led to apparent hepatic I/R injury, manifested by deteriorated liver function, microcirculatory disturbance and increased apoptosis, along with increased PDIA3 expression and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity, and membrane translocation of NADPH oxidase subunits. Treatment with CA attenuated the above alterations. siRNA/shRNA-mediated knockdown of PDIA3 in HL7702 cells and rats played the same role as CA not only in inhibiting ROS production and NADPH oxidase activity, but also in alleviating hepatocytes injury. CA protects transplanted livers from injury, which is likely attributed to its protection of oxidative damage by interfering in PDIA3-dependent activation of NADPH oxidase.

Background The leakage of blood-brain barrier (BBB) is main pathophysiological change in acute stage of ischemic stroke, which not only deteriorates neurological function, but also increases the risk of hemorrhagic transformation after thrombolysis. Purpose/Study Design This article investigates the efficacy of Notoginsenoside R1, an active ingredient of Panax notoginseng, on BBB permeability and explores related mechanisms after acute ischemic stroke. Methods In vivo, male Sprague-Dawley rats (260–280 g) were selected and randomly divided into 6 groups: sham group, model group, low, middle and high doses of Notoginsenoside R1 groups and positive drug Dl-3-n-Butylphthalide group. Except for sham group, rats were performed with permanent middle cerebral artery occlusion model in each group. Twelve hours later, rats were evaluated for Bederson neurological function, and BBB integrity by Evans blue leak imaging; Triphenyltetrazolium chloride staining was used to detect the volume of cerebral infarction. Frozen sections of rats’ brain tissue were prepared for detection of MMPs activity in situ zymography. Peripheral tissue of cerebral infarction was collected and tested the expression of MMP2, 9 and tight junction proteins (zo1, claudin5, occludin) by western blot. In vitro, transwell endothelial barrier model was established by bEnd.3 cells. Oxygen glucose deprivation (OGD) was chosen to simulate the hypoxic environment. Suitable OGD stimulation time as well as Notoginsenoside R1 and Dl-3-n-Butylphthalide optimal dose concentrations were determined through transwell leakage and CCK8 assay. Furthermore, endothelial subcellular component proteins were extracted. The change of zo1, claudin5, occludin and caveolin1 was detected by western blot. Results Notoginsenoside R1 treatment significantly reduced BBB leakage and cerebral infarction volume, weakened neurological deficits in post-stroke rats. Moreover, it inhibited the activity of MMPs in infarcted cortex and striatum, down-regulated MMP2, 9 and up-regulated zo1 and claudin5 expressions in penumbra. In vitro, Notoginsenoside R1 treatment decreased OGD-induced endothelial barrier permeability, restored expressions of zo1, claudin5 on cellular membrane and cytoplasm, as well as mediated membrane redistribution of occludin and caveolin1 from actin cytoskeletal fraction. Conclusions Notoginsenoside R1 treatment attenuates BBB permeability, cerebral infarction volume and neurological impairments in rats with acute cerebral ischemia. The mechanisms might be related to intervening degradation and redistribution of zo1, caludin5 and occludin by caveolin1/ MMP2/9 pathway. More effects and mechanisms of Notoginsenoside R1 on rehabilitation of stroke are worthy to be explored in the future.

Purpose Although osteoporosis is associated with increased risks of complications of fracture fixation in the orthopedic literature, the association between local bone quality (LBQ) and complications of facial fracture fixation is unknown. The authors aim to identify that if decreased LBQ is an independent risk factor for complications following facial fracture fixation? Methods The authors conducted a prospective cohort study on patients over age of 50 years who underwent open reduction and rigid internal fixation for facial fractures. The primary predictor was LBQ (low or normal), decided by a combination of 3 panoramic indices. Other predictors included age, gender, body mass index (BMI), comorbidities, trauma-related characteristics, etc. The outcome variable was the presence of hardware-related, fracture-healing, wound, or neurosensory complications during 2-year follow-up. Univariate and multivariate regressions were performed to identify any significant association between predictor and outcome variables. Results The sample was composed of 69 patients (27 females) with an average age of 58.6 ± 8.6 years and BMI of 25 ± 3.8. Low-LBQ patients were significantly older, more females, had lower BMI, mainly injured from falls, had more complications compared to their normal-LBQ counterparts. However, multivariable logistic regressions demonstrated that only age (adjusted OR: 1.12, P = 0.031, 95% CI: 1.01, 1.23) and diabetes (adjusted OR: 12.63, P = 0.029, 95% CI: 1.3, 122.53) were significantly associated with overall complications after confounding adjustment. Conclusions The results of the present study indicate that reduced LBQ is not an independent risk factor for complications following facial fracture fixation. The increased risk of complications in low-LBQ patients is more likely to be attributed to other age-related comorbidities such as diabetes. Therefore, the authors recommend detailed workup and good control of comorbidities in elderly trauma patient.

Fecal immunochemical testing (FIT) is widely used for colorectal cancer screening, its only indication. Its effect on clinical decision-making beyond screening is unknown. We studied the use of FIT in emergency and inpatient settings and its impact on patient care.Using electronic medical records, we reviewed all non-ambulatory FITs performed from November 2017 to October 2019 at a tertiary care community hospital. We collected data on demographics, indications, gastroenterology consultations, and endoscopic procedures. Multivariate logistic regression was performed to determine the effect of FIT on gastroenterology consultation and endoscopy.We identified 550 patients with at least 1 FIT test. Only 3 FITs (0.5%) were performed for colorectal cancer screening. FITs were primarily ordered from the emergency department (45.3%) or inpatient hospital floor (42.2%). Anemia (44.0%), followed by gastrointestinal bleeding (40.9%), were the most common indications. FIT was positive in 253 patients (46.0%), and gastroenterology consultation was obtained for 47.4% (n = 120), compared with 14.5% (n = 43) of the 297 FIT-negative patients (odds ratio 3.28; 95% confidence interval, 2.23-4.82, P.0001). A potential bleeding source was identified in 80% of patients with reported or witnessed overt gastrointestinal bleeding, a similar proportion (80.7%; P = .92) to patients who were FIT positive with overt gastrointestinal bleeding. Multivariate analysis showed that melena, hematemesis, and a positive FIT were associated with gastroenterology consultation (all P.05), while only melena (odds ratio 3.34; 95% confidence interval, 1.48-7.54) was associated with endoscopy.Nearly all emergency department and inpatient FIT use was inappropriate. FIT resulted in more gastroenterology consultation but was not independently associated with inpatient endoscopy.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.

A 42-year-old male was hospitalized 13.5 hours after ingestion of 50 mg (approximately 0.7 mg/kg) colchicine in a suicide attempt. The patient developed gastrointestinal dysfunction, grade IV myelosuppression, and restrictive respiratory failure without occurrences of cardiovascular collapse or fatal dysrhythmias. Emergency treatment with integrated Chinese and Western medicine was started and the patient fully recovered without long-term complications. This report describes a massive overdose of colchicine successfully treated with integrated Chinese and Western medicine. Current treatment options are reviewed.

Ethnopharmacological relevance Marsdenia tenacissima (Roxb.) Wight & Arn is a well-known traditional Chinese medicine for treating cancer. The anti-tumor effects of the water soluble component of M. tenacissima (MTE, M. Tenacissima Extract) have been intensely studied. However, the roles of microenvironmental cells in mediating the anti-tumor actions of MTE remain to be defined. Aim of the study To determine the roles of nitric oxide (NO) released by endothelial cells (ECs), an important component of tumor microenvironment, in regulating the anti-cancer effects of MTE, and to explore the underlying mechanisms. Materials and methods Co-culture system of ECs and A549 non-small cell lung cancer (NSCLC) cells was established for determining the interactions of ECs and lung cancer cells. Nitro-L-arginine methyl ester hydrochloride (L-NAME) was used to inhibit the production of NO. Cell viability was examined using cell counting kit 8 and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. NO assay and Western blot were used to determine the involved signaling pathway. Primary lung microenvironmental cells (PLMCs) were cultured to examine the roles of NO released from the lung microenvironment in regulating the anti-cancer effects of MTE. A subcutaneous xenograft model was established to determine the involvement of NO in effects of MTE against NSCLCs in vivo. Results In the co-culture system of ECs and A549 NSCLC cells, MTE (30 mg/mL) treatment reduced viability of lung cancer cells. However, when L-NAME (a nitric oxide synthase (NOS) inhibitor, 300 μM) was introduced into the co-culture system, the NSCLC-inhibiting effects of MTE were significantly suppressed. By contrast, addition of L-NAME (300 μM) did not affect the anti-cancer efficiency of MTE when ECs were not present. Mechanistically, MTE enhanced endothelial production of NO via stimulating PKA-endothelial nitric oxide synthase (eNOS) signaling. Elevated levels of NO inhibited proliferation and promoted apoptosis of the A549 NSCLC cells. Importantly, PKA-eNOS-NO signaling was effective in mediating the anti-cancer effects of MTE, when lung cancer cells were co-cultured with PLMCs. Finally, oral administration of MTE to the subcutaneous xenograft mice significantly suppressed tumor growth, while elevated NO productions. Plasma NO was also revealed to be negatively correlated with the tumor weight. Conclusions ECs significantly contributed to anti-cancer effects of MTE by elevating production of NO, in a PKA-dependent manner. The present study revealed a novel anti-cancer mechanism of MTE through regulating the function of ECs, an important component of tumor microenvironment.

Ethnopharmacological relevance Marsdenia tenacissima is a traditional Chinese medicine that is known to be effective in combating cancer as well as reducing blood pressure. The efficacy and mechanisms of Marsdenia tenacissima in treating cancer have been well described. However, the potential vasoactivities of Marsdenia tenacissima remain poorly known. Aim of the study To determine the vasoactive effects of the water-soluble part of marsdenia tenacissima in mesenteric resistance arteries of the mice, and to explore the underlying mechanisms. Materials and methods Isometric vessel tension study was used to examine the effects of marsdenia tenacissima extract (MTE) on vasodilation of the mesenteric arteries of mice. KCl, phenylephrine (PE) and 9,11-Dideoxy-11α,9α-epoxymethanoprostaglandin F2α (U46619) were used as vasoconstrictors. Y27632, Nitro-L-arginine methyl ester hydrochloride (L-NAME) and indomethacin were used to explore the underlying mechanisms for the vasoactivities of MTE. Western blot and nitric oxide (NO) assay were used to evaluate the effects of MTE on the activities of endothelial nitric oxide synthase (eNOS). Results MTE (5–50 mg/mL), but not vehicle, dose-dependently relaxed the mesenteric arteries constricted with KCl, PE or U46619, in which relaxations to KCl were more pronounced than that to PE or U46619. Pre-incubation of the vessels with MTE (40 mg/mL) reduced the vasoconstrictions caused by calcium influx. Decreasing calcium sensitivity by inhibition of Rho kinase (ROCK) significantly augmented the vasorelaxation of MTE. While, inhibition of endothelial cells by pre-incubation with L-NAME (300 μM) and indomethacin (10 μM) or denudating endothelial cells attenuated vasorelaxations of MTE to KCl, and with a larger potency, to U46619. In both human umbilical vein endothelial cells (HUVECs) and human heart microvascular endothelial cells (HMECs), the phosphorylations of eNOS and the production of NO were significantly enhanced after treatment of MTE for 2, 5, 10, 30 min. Conclusions MTE, the water-soluble part of marsdenia tenacissima, was effective in relaxing mesenteric resistance arteries via inhibiting calcium influx and stimulating eNOS activities.

Biological scaffolds based stem cell delivery methods have emerged as a promising approach for tissue repair and regeneration. Here we developed a hydrogel biological scaffold from human decellularized adipose matrix (hDAM) for human adipose-derived stem cells (hASCs) delivery to accelerate chronic wound healing. The hDAM hydrogel was prepared by pepsin mediated digestion and pH controlled neutralization. The morphology, survival, proliferation and angiogenic paracrine activity of hASCs cultured in the hydrogel were assessed. Moreover, the therapeutic efficacy of the hASCs-hydrogel composite for impaired wound healing was evaluated by using a full-thickness wound model on diabetic mouse. The developed hDAM hydrogel was a thermosensitive hydrogel, presented the biochemical complexity of native extracellular matrix (ECM) and formed a porous nanofiber structure after gelation. The hydrogel can support hASCs adhesion, survival and proliferation. Compared to standard culture condition, hASCs cultured in the hydrogel exhibited enhanced paracrine activity with increased secretion of hepatocyte growth factor (HGF). In the diabetic mice model with excisional full-thickness skin wounds, mice treated with the hASCs-hydrogel composite displayed accelerated wound closure and increased neovascularization. Our results suggested that the developed hDAM hydrogel can provide a favorable microenvironment for hASCs with augmented regeneration potential to accelerate chronic wound healing. This article is protected by copyright. All rights reserved.

Since December 2019, an outbreak of COVID-19 sweeping the world. Understanding the clinical and SARS-CoV-2 dynamic changes of mild and ordinary patients of COVID-19, so as to provide basis for the prevention and control of COVID-19. On February 1st, 2020, 16 SARS-CoV-2 RNA positive patients diagnosed in the same site in Beijing. The patients symptoms, signs, medication, and SARS-CoV-2 results were recorded. Of the 16 patients, 12 were female. Although they were infected at the same time in the same workplace, their clinical processes were very different and can be roughly divided into three different types: persistent sputum positive, persistent stool positive and persistent both positive. In 7 patients with mild clinical manifestations, the median days of SARS-CoV-2 RNA negative conversion in sputum samples were significantly later than those with obvious lung injury (27 days [range: 18 to 36]; 17 days, [range 6 to 25], P = .021). The negative conversion of SARS-CoV-2 RNA in stool was significant later than in sputum. There were various clinical manifestations after SARS-CoV-2 infection, even if they were infected by the same source of infection in the same place. The presence of SARS-CoV-2 virus RNA in stool samples was longer than that in respiratory tract.

This study aimed to improve the biological effectiveness and pharmacokinetic properties of chlorin e

The hypomethylation of the Cyclin D1 (CCND1) promoter induced by excess oxidative stress likely promotes the development of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). We aimed to evaluate methylation status of the CCND1 promoter as a new plasma marker for the detection of HBV-HCC. We consecutively recruited 191 participants, including 105 patients with HBV-HCC, 54 patients with chronic hepatitis B (CHB), and 32 healthy controls (HCs). Using methylation-specific polymerase chain reaction, we identified the methylation status of the CCND1 promoter in plasma samples. We analyzed the expression levels of the CCND1 mRNA in peripheral blood mononuclear cells by using quantitative real-time PCR. We assessed the plasma levels of superoxide dismutase, 8-hydroxydeoxyguanosine and malondialdehyde by using enzyme-linked immunosorbent assays. Patients with HBV-HCC (23.81%) presented a reduced methylation frequency compared with patients with CHB (64.81%) or HCs (78.13%) (P

To observe clinical effects of platelet-rich plasma (PRP) intra-articular and extra-articular injection for patients with knee osteoarthritis (KOA), and analyze its safety and clinical efficacy.From January to December 2017, 48 patients with KOA were randomly divided into observation group and control group, 24 cases in each group. The observation group was treated with intra-articular injection of PRP (2 ml) and extra-articular injection of PRP (2 ml), once a week, for three times, including 8 males and 16 females with an average of (58.04±7.87) years old ranging from 43 to 68 years old, the courses of disease ranged from 1 to 8 years with an average of (4.69±1.96) years, the body mass index (BMI) was (24.53±5.26) kg/m 2 . The control group was treated with intra-articular injection of sodium hyaluronate (20 mg), extra-articular injection of analgesic drug (2 ml for one point), once a week, for three times, including 7 males and 17 females with an average of (60.54±8.93) years old ranging from 47 to 72 years old, the courses of disease ranged from 1.5 to 9 years with an average of (5.27±1.68) years, BMI was (23.47±4.62) kg/m 2 . VAS score and Lysholm score before operation and the 1st, 6th month after treatment were compared between two groups.All patients were followed up at least 6 months without occurrence serious adverse reactions or complications. VAS score in observation group and control group before treatment and 1st, 6th month after treatment were 7.35±1.47, 4.15±1.52, 2.26±1.02 and 7.51±1.39, 3.84±1.76, 3.66±1.18, respectively; VAS score in obsevation group was lower than that of control group at 6 months after treatment. Lysholm score in observation group and control group before treatment and 1st, 6th month after treatment were 55.21±5.78, 79.16±7.25, 85.45±6.87 and 54.65± 6.40, 77.58±6.94, 82.34±7.12. There were significant differences in Lysholm score before and after injection between two groups (Intra-articular and extra-articular injection of PRP could relieve pain symptoms and improve function of knee joint with higher safety, although the short-term effect is not significantly different from traditional treatment, its medium-long-term effect is stable. It is a safe and effective method for the treatment of knee osteoarthritis.

OBJECTIVE: To preliminary explore the effect of decellularized adipose tissue (DAT) combined with vacuum sealing drainage (VSD) on wound inflammation in pigs. METHODS: The DAT was prepared through the process of freeze-thaw, enzymatic digestion, organic solvent extraction, and vacuum freeze-drying. The appearance of DAT was observed before and after freeze-drying. HE staining was used to observe its structure and acellular effect. Eighteen male Bama minipigs were recruited, and four dorsal skin soft tissue wounds in diameter of 4 cm were made on each pig and randomly divided into 4 groups for different treatments. The wounds were treated with DAT combined with VSD in DAT/VSD group, DAT in DAT group, VSD in VSD group, and sterile gauze dressing in control group. HE staining was performed at 3, 7, 10, and 14 days after treatment. Moreover, the expressions of inflammatory factors [interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)], as well as the phenotypes of M1 and M2 macrophage phenotypic markers [inducible nitric oxide synthase (iNOS) and arginase 1 (ARG-1)] were detected by real-time fluorescence quantitative PCR (qRT-PCR). ELISA was used to determine the content of iNOS and ARG-1. RESULTS: General observation and HE staining showed that DAT obtained in this study had a loose porous structure without cells. The neutrophils of wounds were significantly less in DAT/VSD group than in control group and DAT group (P0.05) between DAT/VSD group and VSD group. And the neutrophils were significantly less in DAT/VSD group than in other three groups (P

Objective We developed and validated a prediction score for predicting the probability of 6-month and 12-month seizure freedom of antiepileptic drug (AED) treatment in newly diagnosed patients with magnetic resonance imaging (MRI)-negative epilepsy. Methods The development cohort included 543 consecutive patients from the Epilepsy Center of Henan Provincial People's Hospital, while the validation cohorts included 493 consecutive patients in two independent cohorts. Univariate analysis and a forward and backward elimination of multivariate Cox regression analysis were used to select predictive factors. The performance of the score was evaluated with C-index, calibration plots, and decision curve analysis. The risk stratification was also performed. Results The score included five routinely available predictors including Circadian rhythms, Electroencephalography before AED treatment, Neuropsychiatric disorders, Perinatal brain injury, and History of central nervous system infection (CENPH score). When applied to the external validation cohort, the score showed good discrimination with C-index (development group: 0.83; validation group: 0.78), and calibration plots indicated well calibration, as well as the decision curve analysis showed good predictive accuracy and clinical values in four cohorts. The points of the score were categorized to the following three probability levels for predicting seizure freedom: high probability (0–83.11 points), medium probability (83.11–122.71 points), and low probability (> 122.71 points). And online calculator was established to make this score easily applicable in clinical practice. Conclusions We established a simple, practical, and evidence-based prediction score for predicting seizure freedom with AEDs to aid in the clinical consultation and treatment decision for the newly diagnosed patients with MRI-negative epilepsy.

Objective We used a smartphone to construct three-dimensional (3D) models of keloids, then quantitatively simulate and evaluate these tissues. Methods We uploaded smartphone photographs of 33 keloids on the chest, shoulder, neck, limbs, or abdomen of 28 patients. We used the parallel computing power of a graphics processing unit to calculate the spatial co-ordinates of each pixel in the cloud, then generated 3D models. We obtained the longest diameter, thickness, and volume of each keloid, then compared these data to findings obtained by traditional methods. Results Measurement repeatability was excellent: intraclass correlation coefficients were 0.998 for longest diameter, 0.978 for thickness, and 0.993 for volume. When measuring the longest diameter and volume, the results agreed with Vernier caliper measurements and with measurements obtained after the injection of water into the cavity. When measuring thickness, the findings were similar to those obtained by ultrasound. Bland–Altman analyses showed that the ratios of 95% confidence interval extremes were 3.03% for longest diameter, 3.03% for volume, and 6.06% for thickness. Conclusion Smartphones were used to acquire data that was then employed to construct 3D models of keloids; these models yielded quantitative data with excellent reliability and validity. The smartphone can serve as an additional tool for keloid diagnosis and research, and will facilitate medical treatment over the internet.

Thallium, a highly toxic heavy metal and priority pollutant, has been widely reported to cause neurodevelopmental toxicity in animals. However, accessible epidemiological studies concerning the neurodevelopmental toxicity of early-life thallium exposure in humans are limited. In a prospective birth cohort including 2164 mother-child pairs, we explored the effect of prenatal serum thallium exposure on cognitive development among preschool-aged children born in Ma'anshan, Anhui, China. Serum thallium concentrations were measured in the first trimester, second trimester, third trimester, and cord blood by inductively coupled plasma mass spectrometry (ICP-MS). Child cognitive development was appraised by the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) at 4.5 years old. Multiple informants generalized estimating equations (GEEs) were fit to jointly estimate the association between the four repeated measurements of thallium concentrations and the preschool-aged children's cognitive test scores. After adjusting for potential confounders, the visual spatial index (VSI) was 1.45 points lower in the highest tertile of serum thallium during the first trimester than in the lowest tertile (p for trend = 0.04). Moreover, children in the highest tertile of serum thallium during the third trimester had a significantly lower full-scale intelligence quotient (FSIQ) (β = −1.51, 95% CI: 2.68, −0.35), VSI (β = −1.79, 95% CI: 3.16, −0.42), fluid reasoning index (FRI) (β = −1.41, 95% CI: 2.73, −0.10), and processing speed index (PSI) (β = −1.47, 95% CI: 2.71, −0.24) scores than the children in the lowest tertile. When performing stratified analysis by child sex, the associations of first- and third-trimester thallium concentrations with cognitive test scores were more prominent in boys than in girls. Our findings revealed that maternal serum thallium exposure during the first and third trimesters, but not other periods, had detrimental effects on preschoolers' cognitive development, and these effects showed sex differences.

Background The phenotypes of osteoarthritis (OA) consist of cartilage extracellular matrix (ECM) metabolism disorder and the breakdown of cartilage homeostasis, which are induced by pro-inflammatory factors and oxidative stress. Selenoproteins regulated by selenocysteine insertion sequence binding protein 2 (SBP2) are highly effective antioxidants, but their regulatory mechanisms, particularly the involvement of miRNAs, are not fully understood. Methods To explore whether miR-181a-5p and SBP2 are involved in OA pathogenesis, we established an IL-1β model using the chondrocyte SW1353 cell line. Next, we up- or down-regulated SBP2 and miRNA-181a-5p expression in the cells. Finally, we measured the expression of miRNA-181a-5p, SBP2 and three selenoproteins in OA cartilage and peripheral blood. Results The results showed that IL-1β increased hsa-miR-181a-5p and decreased SBP2 in a time- and dose-dependent manner. GPX1 and GPX4, which encode crucial glutathione peroxidase antioxidant enzymes, were up-regulated along with SBP2 and miR-181a-5p. Furthermore, SBP2 showed a significant negative correlation with miR-181a-5p during induced ATDC5 cell differentiation. There was lower GPX1 and GPX4 mRNA expression and SBP2 protein expression in damaged cartilage than in smooth cartilage from the same OA sample, and hsa-miR-181a-5p expression on the contrary. Similar results were observed in peripheral blood. In conclusion, we have reported a novel pathway in which pro-inflammatory factors, miRNA, SBP2 and selenoproteins are associated with oxidation resistance in cartilage. Conclusion Overall, this study provides the first comprehensive evidence that pro-inflammatory factors cause changes in the cartilage antioxidant network and describes the discovery of novel mediators of cartilage oxidative stress and OA pathophysiology. Our data suggest that miR-181a-5p may be used to develop novel early-stage diagnostic and therapeutic strategies for OA. Electronic supplementary material The online version of this article (10.1186/s12891-018-2273-6) contains supplementary material, which is available to authorized users.

To the best of our knowledge, no study has reported pediatric jaw lesions according to the latest World Health Organization (WHO) classification of head and neck tumors. We reviewed the spectrum of benign pediatric jaw lesions treated at the Massachusetts General Hospital during a 13-year period according to the 2017 WHO classification.We implemented a retrospective cohort study of patients younger than 18 years old with benign bony lesions. The primary predictor variable was the histopathologic diagnosis, grouped into odontogenic tumors (OTs), non-OTs, and odontogenic cysts. The primary outcome variables were the incidence of recurrence and the interval to recurrence. Other outcome variables included symptoms, radiographic findings, and treatment modalities. Descriptive statistics were computed. Kaplan-Meier analyses and Cox regressions were performed.The sample included 131 patients (58 males and 73 females; mean age, 12.6 ± 3.7 years) with 14 pathologic diagnoses. These were grouped as follows: non-OTs (n = 67), OTs (n = 36), and odontogenic cysts (n = 28). Odontogenic cysts were predominantly radiolucent, unilocular, and well-circumscribed cysts compared with the OTs and non-OTs (P .05). Enucleation was the most commonly performed surgical procedure (72.5%). Adjuvant nonoperative procedures included cryotherapy for 10 patients, interferon therapy for 9 patients, and chemotherapy with denosumab for 3 patients to treat aggressive tumors. The overall incidence of recurrence was 0.77/100 person-years. The Cox hazard ratio of non-OTs/OTs was 3.1 (P = .13) and cysts/OTs was 4.3 (P = .075). Neither the incidence of recurrence nor the interval to recurrence among the 3 groups showed significant differences. A high incidence of recurrence was noted for aggressive central giant cell tumors (39.1%) and odontogenic keratocysts (40%) during a median follow-up of 3 years.Although pediatric jaw lesions are uncommon, symptoms such as swelling could indicate potential pathologic findings and require panoramic examination. Management of pediatric jaw lesions should consider the biologic behavior of the lesion, maxillofacial development, and growth. Enucleation combined with pharmacologic therapy is a promising strategy for the management of aggressive central giant cell tumors in children.

The interplay between anabolic and catabolic factors regulates cartilage matrix homoeostasis. In OA, this balance is disrupted which results in cartilage degradation involving a plethora of inflammatory factors. Here, we identify a novel gene “Scm‐like with four MBT domains protein 2” (SFMBT2) negatively regulated in OA cartilage. Articular cartilage from human OA patients undergoing knee arthroplasty surgery exhibited significantly decreased levels of SFMBT2 compared to the normal controls. Down‐regulation of SFMBT2 by specific siRNA disturbed the metabolic homoeostasis and led to decreased expression of anabolic genes (SOX9, COL2A1) while increasing the expression of catabolic genes (MMP13 and ADAMTS4), in human chondrocytes. Finally, we revealed that SFMBT2 intervention by siRNA contributed to the catabolic phenotype of human chondrocytes mediated by NF‐kB pathway.

MicroRNA-142-5p (miR-142-5p) has been found to be dysregulated in several neurodegenerative disorders. However, little is known about the involvement of miR-142-5p in Alzheimer's disease (AD). Brain angiogenesis inhibitor 3 (BAI3), which belongs to the adhesion-G protein-coupled receptor subgroup, contributes to a variety of neuropsychiatric disorders. Despite its very high expression in neurons, the role of BAI3 in AD remains elusive, and its mechanism at the cellular and molecular levels needs to be further elucidated. The current study sought to investigate whether miR-142-5p influenced BAI3 expression and neuronal synaptotoxicity induced by Aβ, both in APP/PS1 transgenic mice and a cellular model of Alzheimer's disease. Altered expression of miR-142-5p was found in the hippocampus of AD mice. Inhibition of miR-142 could upregulate BAI3 expression, enhance neuronal viability and prevent neurons from undergoing apoptosis. In addition, the reduction of phosphorylation of Synapsin I and calcium/calmodulin-dependent protein kinase II (CaMKII), as well as the expression of PSD-95 in the hippocampus of APP/PS1 transgenic mice, were significantly restored by inhibiting miR-142. Meanwhile, the levels of Aβ1-42, β-APP, BACE-1 and PS-1 in cultured neurons were detected, and the effects of inhibiting miR-142 on spatial learning and memory were also observed. Interestingly, we found that BAI3, an important regulator of excitatory synapses, was a potential target gene of miR-142-5p. Collectively, our findings suggest that miR-142 inhibition can alleviate the impairment of spatial learning and memory, reduce the level of apoptosis, and upregulate the expression of pCaMKII and BAI3 in the hippocampus of APP/PS1 transgenic mice; thus, appropriate interference of miR-142 may provide a potential therapeutic approach to rescue cognitive dysfunction in AD patients.

Background: Childhood nephrotic syndrome is widespread in pediatric nephrology. In most cases, it needs hospitalization for patient management. An increasing number of studies report that proper nursing care could promote the rate of treatment and improve post-treatment prognosis. Clinical nursing pathways refer to innovative nursing modes with high-quality, excellent efficacy, and low costing treatment. There are reports on how nursing methods that utilize data combine with clinical nursing pathway to enhance nephrotic syndrome care in kids. However, the results remain controversial. Therefore, it is necessary to conduct this study to systematically explore how evidence-based nursing combined with clinical nursing pathway plays a role in nephrotic syndrome care among children. Methods: This study protocol will conduct a comprehensive search on MEDLINE, Cochrane Library, CINAHL, EMBASE, Scopus, Chinese National Knowledge Infrastructure, WanFang, and Web of Science electronic databases to identify relevant research articles from inception to April 25, 2021. Studies in both English and Chinese languages are used for this study. This study protocol will analyze randomized controlled trials that investigated the role of evidence-based nursing combined with clinical nursing pathway to care for nephrotic syndrome in children. Two authors will independently screen the search results, select suitable studies for inclusion, extract the characteristics and outcome data of the selected studies, and evaluate the risk of bias based on standard Cochrane methodology. Any discrepancies will be resolved by consensus. Results: The present study will summarize high-quality evidence to systematically explore how a nursing model based on evidence combined with clinical nursing pathway influences the caring of children with nephrotic syndrome. Conclusion: The present study will summarize the direct and indirect evidence to judge whether evidence-based nursing combined with clinical nursing pathway can improve the treatment and post-treatment prognosis in children with nephrotic syndrome. Ethics and dissemination: This study does not require an ethical approval. Registration number: April 25, 2021.osf.io/bcrdk/ (https://osf.io/bcrdk/).

Colorectal cancer is one of the most frequent malignancies in the world. Tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family and a coregulator for multiple nuclear receptors. Altered expression of TRIM24 has been shown in a spectrum of human cancers. However, the clinical role of TRIM24 in colorectal cancer remains unknown. Here, gene expression data in colorectal cancer and normal tissues were downloaded from Gene Expression Omnibus (GEO). Western blotting analysis was conducted to compare TRIM24 expression between colorectal cancer and non-cancerous tissues. Immunohistochemistry staining were performed to assess TRIM24 expression in colorectal cancer tissues, and statistical analyses were employed to evaluate the associations of TRIM24 expression with clinicopathologic features and overall survival. TRIM24 mRNA and protein levels were higher in colorectal cancer tissues than that in the normal controls. TRIM24 protein expression was positively correlated with tumor size (P=0.0269), clinical stage (P=0.0061), vital status (P=0.0110) and serum carcinoembryonic antigen levels (P=0.0176). Kaplan-Meier survival analysis indicated that patients with higher TRIM24 expression had shorter survival time than those with lower TRIM24 expression. Multivariate analyses revealed TRIM24 expression was an independent prognostic factor (P

Objectives Many medical schools in Taiwan have adopted a dignified “silent mentor” initiation ceremony to strengthen student’s medical humanity and increase their learning attitudes. This ceremony consists of introductions of the body donor’s conduct and deeds, wreath-laying, and a tea party. However, few empirical studies have examined the influences of the ceremony and dissection on medical humanity. This study explored if the initiation ceremony and the course can help students care more about others, develop more positive attitudes toward death, improve learning effectiveness in the course, and decrease negative emotions the first time they see a cadaver. Methods The Attitudes Towards Death and Love and Care subscales of the life attitude inventory, Learning Effectiveness of Gross Anatomy Laboratory Scale (LEGALS), and Emotional Reactions Towards Cadavers Scale were adopted to examine differences before (T1) and after (T2) medical students attended an initiation ceremony at a university in northern Taiwan. Whether these effects lasted to the end of the semester (T3) was also tested. Results After the ceremony, students’ attitudes towards death increased, negative emotions towards cadavers decreased, but love and care and the LEGALS did not significantly change. Data from T3 showed a similar pattern, but high-level emotions (e.g., being respected, cherished, and grateful) and the LEGALS were significantly higher than those at T1. Discussion The initiation ceremony, which showed a body donor’s deeds and attitudes toward life and death when they were alive, could help medical students gain more mature attitudes towards death and decreased negative emotions. Learning between T2 and T3 might have caused significant changes in high-level emotions and the LEGALS at T3. Arranging reflective writing with guided discussion by a teacher before and after the ceremony is highly recommended.