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Background: Spontaneous intracerebral hemorrhage (sICH) is a critical and disabling form of stroke and accounts for an obvious number of stroke-related deaths and disabilities globally. Hematoma growth is a key target for therapeutic intervention because of its association with poor outcomes. Recently, the STOP-MSU trial showed that intravenous tranexamic acid (TA) did not reduce hematoma growth or improve clinical outcomes when administered within 2 h of intracerebral hemorrhage symptom onset. This study aims to evaluate the efficacy of TA in reducing hematoma growth and improving clinical outcomes in patients with spontaneous sICH by incorporating the findings from the latest STOP-MSU trial and consolidating past research to clarify the overall efficacy and safety of TA on sICH., Methods: A systematic review and meta-analysis were conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. We included randomized controlled trials (RCTs) comparing TA to placebo in adult patients with sICH. Databases such as PubMed, Medline, and Cochrane were searched up to May 2024. Key outcomes analyzed included hematoma expansion, mortality within 90 days, thromboembolic events, and favorable functional outcomes. Data were pooled using a random-effects model and analyzed using the "metafor" package in RStudio., Results: Five RCTs involving 1419 patients were included. The meta-analysis showed no significant difference in hematoma expansion (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.74-1.03), mortality within 90 days (OR 1.03, 95% CI 0.86-1.24), thromboembolic events (OR 1.07, 95% CI 0.69-1.64), and favorable functional outcomes (modified Rankin Scale of 0-2 at 90 days; OR 1.04, 95% CI 0.88-1.22) between the TA and placebo groups., Conclusions: TA does not significantly reduce hematoma growth or improve clinical outcomes in patients with sICH. Despite its affordability and availability, the routine use of TA in sICH is not supported by current evidence., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable for systematic review/meta-analysis., (© 2025. The Author(s).)

Introduction: Hypoxemia is a common complication of sedation. This meta-analysis aimed to evaluate the efficacy and safety of supraglottic jet oxygenation and ventilation (SJOV) in preventing hypoxemia during sedative procedures., Methods: Randomized controlled trials (RCTs) that compared SJOV with conventional oxygen therapy in sedated patients were searched in five databases (MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure [CNKI], and Google Scholar) from their inception to March 2024. The primary outcome was the proportion of patients who developed hypoxia (SpO 2  < 90%). The secondary outcomes included subclinical respiratory depression (90% ≤ SpO 2  < 95%), severe hypoxemia (SpO 2  < 75%), airway interventions, adverse events, hemodynamics, propofol dosage, and procedure time. The certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Twelve trials (n = 3058) were included in the analysis. The evidence suggests that SJOV results in a large reduction in the risk of hypoxemia (risk ratio [RR], 0.26; 95% confidence interval, 0.19-0.36; low certainty) and subclinical respiratory depression (RR, 0.40; low certainty) compared with the control. SJOV likely resulted in a large reduction in the risk of severe hypoxemia (RR, 0.22; moderate certainty). In addition, it may result in a large reduction in the need for jaw lift (RR, 0.22; low certainty) and mask ventilation (RR, 0.13; low certainty). The risk of sore throat probably increases with SJOV (RR, 1.71; moderate certainty), whereas SJOV may result in little to no difference in nasal bleeding (RR, 1.75; low certainty). Evidence is very uncertain regarding the effect of SJOV on hemodynamics (very low certainty) and procedure time (very low certainty). SJOV probably resulted in little to no difference in sedative doses between the groups (moderate certainty)., Conclusion: According to the GRADE approach, SJOV likely results in a large reduction in the risk of severe hypoxemia but probably increases the risk of sore throat. Compared with the control, evidence suggests that SJOV results in a large reduction in the risk of hypoxemia, subclinical respiratory depression, and the need for airway manipulation, with little to no difference in nasal bleeding. The integration of SJOV into clinical practice may help minimize hypoxemic events in at-risk patients., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia., Methods: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses., Results: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I 2  = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I 2  = 0%) but not in the ward., Conclusion: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement., (© 2024. The Author(s).)

Objective: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment., Methods: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues., Results: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy., Conclusion: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions., (© 2024. The Author(s).)

Background: The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis., Methods: A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis's evidence., Results: The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58-0.74) and 0.74 (95% CI 0.67-0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99-3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37-0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80-8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI's sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p < 0.05) and in studies excluding patients with chronic kidney disease (CKD) than in those including them (0.75 vs. 0.56; p < 0.01). Overall, diagnostic performance was superior in the non-chronic kidney disease group., Conclusion: Our study demonstrated that PNI has practical accuracy for predicting the development of AKI in critically ill populations, with superior diagnostic performance observed in medical and non-CKD populations. However, the diagnostic efficacy of the PNI has significant heterogeneity with different cutoff value, indicating the need for further research., (© 2024. The Author(s).)

Background: To shorten the preoperative preparation time, reconstruction plates were designed using the computed tomography (CT)-based three-dimensional (3D) medical imaging surgical planning software OOOPDS. In addition, 3D printing was used to generate curved plates for anterior pelvic fracture surgeries., Methods: This study analyzed two groups with the same 21 patients who underwent surgery for traumatic anterior pelvic ring fractures. In Group 1, the direct reconstruction plates were preoperatively contoured according to the anatomical 3D-printed pelvic model. In Group 2, the fixation plates were contoured according to the 3D printed plate templates, which were created based on the simulated plate templates by the OOOPDS software. The processing time, including the 3D printing time for the pelvic models in Group 1, the 3D printing time for the fixation plate templates in Group 2, and the pre-contouring time for the plates in both groups, was recorded., Results: The mean time of pre-contouring for the curved reconstruction plates in Group 2 was significantly less than in Group 1 (-55 min; P < 0.01). The mean time of 3D printing for the 3D plate template model in Group 2 was significantly less than that for the 3D pelvic model in Group 1 (-869 min; P < 0.01). Experimental results showed that the printing time for the plate pre-contouring and the 3D plate templates could be effectively reduced by approximately 93% and 90%, respectively., Conclusion: This method can shorten the preoperative preparation time significantly., (© 2023. The Author(s).)

Background: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury., Methods and Results: Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 10 6 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001)., Conclusion: Mel-ADMSCs effectively protected the testis against TTIR injury.

Background: Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers., Methods: In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR., Results: Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients' restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively., Conclusions: The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.

Background: Acromioclavicular joint (ACJ) dislocation is a relatively common shoulder injury. For the treatment of cases of severe ACJ dislocation (Rockwood type III-V), hook plate fixation is an easy-to-master and minimally-invasive approach to surgical intervention. Over stress on the acromion following hook plate fixation often leads to acromial complications such as osteolysis and loss of reduction. We hypothesized that suspensory reconstruction alongside hook plate fixation might provide a superior stability and reduce complications as compared with hook plate fixation alone. The purpose of the study was to assess the clinical and radiographic outcomes of these two surgical modalities., Methods: We retrospectively enrolled 49 patients with acute ACJ dislocation from May 2010 to December 2018. Among them, 19 patients received hook plate fixation only (HP group), and 19 underwent concomitant hook plate fixation and loop suspension fixation with two mersilene sutures (HM group). The demographic data of the patients were recorded and analyzed. All patients underwent a shoulder X-ray initially, immediately postoperatively, and at 1, 3, 6 and 12 months to measure the relative coracoclavicular distance (rCCD). Clinical assessment of shoulder function outcome was conducted using the Constant Murley Score (CMS); the University of California at Los Angeles (UCLA) Shoulder Score was also measured at the latest follow-up., Results: There were no significant differences in the demographic data between the two groups. With regards to the CMS and the UCLA score, the HM group and HP group both had excellent outcomes, and no significant differences in scores were observed between groups (CMS: 93.90 ± 6.16 versus 94.47 ± 7.26, p = 0.47; UCLA score: 32.84 ± 2.91 versus 34.32 ± 1.16, p = 0.07). However, the HM group demonstrated substantial superiority in terms of maintenance of the rCCD over the HP group (91.47 ± 27.47 versus 100.75 ± 48.70, p = 0.015). In addition, there was less subacromial osteolysis in the HM group than the HP group (52.6% versus 15.8%, p = 0.038)., Conclusion: Both fixations yielded excellent functional outcomes. However, concomitant hook plate fixation with loop suspensory reconstruction demonstrated the fewer acromion complications and statistical differences in reduction maintenance with less clinical significance.

Background: The Nelson mortality results were presented in September 2018. Four other randomized control trials (RCTs) were also reported the latest mortality outcomes in 2018 and 2019. We therefore conducted a meta-analysis to update the evidence and investigate the benefits and harms of low-dose computed tomography (LDCT) in lung cancer screening., Methods: Detailed electronic database searches were performed to identify reports of RCTs that comparing LDCT to any other type of lung cancer screening. Pooled risk ratios (RRs) were calculated using random effects models., Results: We identified nine RCTs (n = 97,244 participants). In pooled analyses LDCT reduced lung cancer mortality (RR 0.83, 95% CI 0.76-0.90, I 2  = 1%) but had no effect on all-cause mortality (RR 0.95, 95% CI 0.90-1.00). Trial sequential analysis (TSA) confirmed the results of our meta-analysis. Subgroup defined by high quality trials benefitted from LDCT screening in reducing lung cancer mortality (RR 0.82, 95% CI 0.73-0.91, I 2  = 7%), whereas no benefit observed in other low quality RCTs. LDCT was associated with detection of a significantly higher number of early stage lung cancers than the control. No significant difference (RR 0.64, 95% CI 0.30-1.33) was found in mortality after invasive procedures between two groups., Conclusions: In meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival. The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, Asian) being screened.

Background: We tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120., Methods: A total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508)., Results: On Day 3, urine and bladder specimens were collected for biochemical, histopathological, immunological, and immunoblotting analysis. Following stimulation with cyclophosphamide, the inhibition of the elevated levels of TAK1/NF-κB and phospho-TAK1/NF-κB by ESWT and GPR120 agonists in RT4 cells was associated with a suppression of NF-κB translocation from the cytosol to the nucleus. Accordingly, this anti-inflammatory effect was abolished by GPR120 antagonist and knockdown of GPR120. Histologically, bladder inflammation in cyclophosphamide-treated rats was suppressed by GW9508 or ESWT. Masson's trichrome and Sirius red staining revealed that cyclophosphamide treatment enhanced synthesis of extracellular matrix in rats that was reversed by GW9508 or ESWT. Upregulated pro-inflammatory mediators and cytokines in the cyclophosphamide-treated rats were also suppressed in the GW9508- or ESWT-treated rats. The significantly increased inflammatory cell infiltration as well as the impaired urothelial integrity of the bladder after cyclophosphamide treatment were reversed by treatment with GW9508 or ESWT., Conclusions: These findings suggest that GPR120, the sensing receptor for ESWT, may be useful in the treatment of interstitial cystitis by inhibiting inflammatory response in bladder cells.

Background: Pelvic ring injuries constitute only 2 to 8% of all fractures; however, they occur in 20% of polytrauma patients. High-energy pelvic fractures often result in mechanical instability of the pelvic ring. Successful treatment of unstable pelvic ring fractures remains a challenge for orthopedic surgeons. This study presents a novel internal fixation method for stabilizing unstable anterior pelvic ring fractures using a minimally invasive modified pedicle screw-rod fixation (MPSRF) technique., Methods: This retrospective study included six patients with unstable pelvic ring injuries who underwent MPSRF, with or without posterior fixation. Intraoperative parameters such as blood loss, operative time, complications, and quality of reduction (Matta criteria) were recorded and evaluated by a blinded reviewer., Results: In the present clinical series, the mean operative times and mean blood loss for unilateral versus bilateral anterior ring fixations were 176.0 min versus 295.6 min, and 153.3 mL versus 550.0 mL, respectively. No iatrogenic neuropraxia of the lateral femoral cutaneous nerve or femoral nerve palsy occurred. The reduction quality, graded by the Matta criteria, was excellent in five patients and good in one patient., Conclusions: There were no infections, delayed unions, nonunions, or loss of reductions during the follow-up period. Only one patient suffered from a broken rod at 4 months postoperatively. The modified technique represents a novel, minimally invasive procedure for the treatment of anterior pelvic ring fractures and offers a reliable and effective alternative to currently available surgical techniques.

Background: Emergency complications of colon cancer include perforation and obstruction which were recognized as poor prognostic factors. Few studies have directly compared the outcomes of these two groups. In this study, we evaluated mortality and morbidity in patients with colon cancer initially presenting as perforation and obstruction., Methods: Newly diagnosed colon cancer cases initially presenting with perforation or obstruction at Tzu Chi General Hospital, Hualien, Taiwan, between 2009 and 2015 were included. Cases of iatrogenic perforation or perforation sites far away from the tumor sites and rectal (< 15 cm from the anal verge) cancer were excluded. Progression-free survival, local recurrence rate, distant metastasis rate, and overall survival were the evaluated outcomes., Results: Eighty-one patients met the selection criteria; 23 and 58 patients had perforation and obstruction, respectively, as the initial symptom. The median age was 72 years. The median tumor stage was stage IIIB. The 1-year and 3-year survival rates were 83.7 and 59.7%, respectively. The perforation group (PRG) and obstruction group (OBG) did not differ significantly in intensive care unit (ICU) stay rate (p = 0.147), sex (p = 0.45), comorbidities (heart, liver, and renal diseases and diabetes mellitus), median stage (p = 0.198), and overall survival (p = 0.328). However, PRG had a higher age at diagnosis (74 vs. 64 years, p = 0.037), a higher APACHE II score (12 vs. 7, p = 0.002), lower disease-free survival (p = 0.001), a higher recurrence rate (56.5 vs. 19%, p = 0.002), a higher distant metastasis rate (39.1 vs. 13.8%, p = 0.015), and a higher local recurrence rate (43.5 vs. 5.2%, p < 0.001) than did OBG. OBG had a higher two-stage operation rate (46.6 vs. 17.4%, p = 0.022). After adjustment for the tumor stage, comorbidity (chronic renal disease), body mass index (BMI), and adjuvant chemotherapy or radiotherapy in multivariate statistics, PRG had lower disease-free survival (p = 0.005) than OBG but overall survival was identical., Conclusion: For colon cancer initially presenting as perforation or obstruction, the PRG had poorer progression-free survival, a higher local recurrence rate, and a higher distant metastasis rate than did OBG. Overall survival did not differ between these two groups.

Background: The cellular immune response for Mycobacterium tuberculosis (M. tuberculosis) infection remained incompletely understood. To uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed M. tuberculosis (HKTB) treatment., Results: Organic solvent-assisted trypsin digestion coupled with stable-isotope labeling and LC-MS/MS analysis was applied to quantitatively analyze the membrane protein expression of THP-1 derived dendritic cells. We evaluated proteins that were upregulated in response to HKTB treatment, and applied STRING website database to analyze the correlations between these proteins. Of the investigated proteins, aminopeptidase N (CD13) was found to be largely expressed after HKTB treatment. By using confocal microscopy and flow cytometry, we found that membranous CD13 expression was upregulated and was capable of binding to live mycobacteria. Treatment dendritic cell with anti-CD13 antibody during M. tuberculosis infection enhanced the ability of T cell activation., Conclusions: Via proteomics data and STRING analysis, we demonstrated that the highly-expressed CD13 is also associated with proteins involved in the antigen presenting process, especially with CD1 proteins. Increasing expression of CD13 on dendritic cells while M. tuberculosis infection and enhancement of T cell activation after CD13 treated with anti-CD13 antibody indicates CD13 positively involved in the pathogenesis of M. tuberculosis.

Background: The source and sink relationships between insect-induced galls and host plant leaves are interesting. In this research, we collected cup-like galls induced by Bruggmanniella sp. (Diptera: Cecidomyiidae) on host leaves of Litsea acuminata and assessed them to investigate source-sink relationships between galls and host leaves. We characterized several of their photosynthetic characteristics including chlorophyll fluorescence (Fv/Fm), stomatal conductance, and photosynthetic capacity, biochemical components such as total soluble sugar, starches, free amino acids, and soluble proteins. The structural analyses were performed under confocal, light, and scanning electron microscopies., Results: Compared with host leaves, galls exhibited slightly lower chlorophyll fluorescence; however, stomatal conductance and photosynthetic capacity were not detected at all. Galls accumulated higher total soluble sugars and free amino acids but less soluble proteins than host leaves. No stomata was observed on exterior or interior gall surfaces under light or scanning electron microscopy, but their inner surfaces were covered with fungal hyphae. Confocal imagery showed a gradient of chloroplasts distribution between gall outer and inner surfaces., Conclusions: Our results strongly suggest that leaf-derived cecidomyiid galls are a type of chlorophyll-deficient non-leaf green tissue and consists on a novel sink in L. acuminate.

Background: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury., Methods: Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2-4)., Results: Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01)., Conclusion: Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.

Background: In a previous study, we showed that the cephalochordate amphioxus Branchiostoma floridae has localized maternal transcripts of conserved germ cell markers Vasa and Nanos in its early embryos. These results provided strong evidence to support a preformation mechanism for primordial germ cell (PGC) development in B. floridae., Results: In this study, we further characterize the expression of B. floridae homologs of Piwi and Tudor, which play important roles in germline development in diverse metazoan animals. We show that maternal mRNA of one of the identified Piwi-like homologs, Bf-Piwil1, also colocalizes with Vasa in the vegetal germ plasm and has zygotic expression in both the putative PGCs and the tail bud, suggesting it may function in both germline and somatic stem cells. More interestingly, one Tudor family gene, Bf-Tdrd7, is only expressed maternally and colocalizes with Vasa in germ plasm, suggesting that it may function exclusively in germ cell specification. To evaluate the conservation of the preformation mechanism among amphioxus species, we further analyze Vasa, Nanos, Piwil1, and Tdrd7 expression in two Asian amphioxus species, B. belcheri and B. japonicum. Their maternal transcripts all localize in similar patterns to those seen in B. floridae. In addition, we labeled putative PGCs with Vasa antibody to trace their dynamic distribution in developing larvae., Conclusions: We identify additional germ plasm components in amphioxus and demonstrate the molecular distinction between the putative germline stem cells and somatic stem cells. Moreover, our results suggest that preformation may be a conserved mechanism for PGC specification among Branchiostoma species. Our Vasa antibody staining results suggest that after the late neurula stage, amphioxus PGCs probably proliferate with the tail bud cells during posterior elongation and are deposited near the forming myomere boundaries. Subsequently, these PGCs would concentrate at the ventral tip of the myoseptal walls to form the gonad anlagen.

Introduction: This study tested the hypothesis that cyclosporine (CsA)-supported syngeneic adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury to either therapy alone., Methods: Adult Sprague-Dawley rats (n = 40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 (IR + CsA (20 mg/kg at 1 and 24 hours after procedure)), group 4 (syngeneic ADMSC (1.2×106) at 1, 6 and 24 hours after procedure), and group 5 (IR + CsA-ADMSC)., Results: By 72 hours after the IR procedure, the creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, and significantly higher in groups 3 and 4 than in group 5 (all P <0.05 for inter-group comparisons), but showed no differences between groups 3 and 4 (P >0.05). The inflammatory biomarkers at mRNA (matrix metalloproteinase-9, RANTES, TNF-α), protein (TNF-α, NF-κB, intercellular adhesion molecule-1, platelet-derived growth factor), and cellular (CD68+) levels of IR kidney showed a similar pattern compared with that of creatinine in all groups (all P <0.05 for inter-group comparisons). The protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NADPH oxidases NOX-1, NOX-2), apoptosis (Bcl-2-associated X protein, caspase-3 and poly(ADP-ribose) polymerase) and DNA damage (phosphorylated H2A histone family member X-positive, proliferating cell nuclear antigen-positive cells) markers exhibited a pattern similar to that of inflammatory mediators amongst all groups (all P <0.05 for inter-group comparisons). Expressions of antioxidant biomarkers at cellular (glutathione peroxidase, glutathione reductase, heme oxygenase-1 (HO-1)) and protein (NADPH dehydrogenase (quinone)-1, HO-1, endothelial nitric oxide synthase) levels, and endothelial progenitor cell markers (C-X-C chemokine receptor type 4-positive, stromal cell-derived factor-1α-positive) were lowest in groups 1 and 2, higher in groups 3 and 4, and highest in group 5 (all P <0.05 for inter-group comparisons)., Conclusion: Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury.

Background: Nonylphenol (NP), an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS) synthesis. Chronic exposure to low-dose adenine (AD) has been reported to induce chronic kidney disease (CKD)., Methods: In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control), group 2 (AD in fodder at a concentration of 0.25%), group 3 (NP: 2 mg/kg/day), group 4 (combined AD & NP), and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day). Treatment was continued for 24 weeks for all animals before being sacrificed., Results: By the end of 24 weeks, serum blood urea nitrogen (BUN) and creatinine levels were increased in group 4 than in groups 1-3, but significantly reduced in group 5 as compared with group 4 (all p < 0.05). Histopathology scorings of renal-parenchymal and tubular damages were significantly higher in group 4 than in groups 1-3, but remarkably lower in group 5 compared with group 4 (all p < 0.01). Both gene and protein levels of inflammation, oxidative stress, ROS, and cellular apoptosis were remarkably higher in group 4 compared with groups 1-3, but lowered in group 5 than in group 4 (all p < 0.001). Conversely, both gene and protein levels of anti-oxidants, anti-inflammation and anti-apoptosis were markedly increased in group 5 compared with group 4 (all p < 0.001)., Conclusion: NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

Background: Successful reproductive efforts require the establishment of a situation favorable for reproduction that requires integration of both behavior and internal physiological events. TR4 nuclear receptor is known to be involved in male fertility via controlling spermatogenesis, yet its roles in regulating other biological events related to reproduction have not been completely revealed., Methods: Male TR4 knockout (TR4 -/-) and wild type mice were used for the sexual behavior and penile dysfunction studies. Mice were sacrificed for histological examination and corresponding genes profiles were analyzed by quantitative RT-PCR. Reporter gene assays were performed., Results: We describe an unexpected finding of priapism in TR4 -/- mice. As a transcriptional factor, we demonstrated that TR4 transcriptionally modulates a key enzyme regulating penis erection and neuronal nitric oxide synthese NOS (nNOS). Thereby, elimination of TR4 results in nNOS reduction in both mRNA and protein levels, consequently may lead to erectile dysfunction. In addition, male TR4 -/- mice display defects in sexual and social behavior, with increased fear or anxiety, as well as reduced mounting, intromission, and ejaculation. Reduction of ER alpha, ER beta, and oxytocin in the hypothalamus may contribute to defects in sexual behavior and stress response., Conclusions: Together, these results provide in vivo evidence of important TR4 roles in penile physiology, as well as in male sexual behavior. In conjunction with previous finding, TR4 represents a key factor that controls male fertility via regulating behavior and internal physiological events.

Background: Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE). Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE., Methods: We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7) rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry., Results: Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats., Conclusion: These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

Background: Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury., Methods: Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed., Results: Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02), Conclusion: ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.