Dose-response study of propofol combined with two different doses of esketamine for laryngeal mask airway insertion in women undergoing hysteroscopy.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

Case report: Anesthetic management for removal of tumor thrombus in the inferior vena cava and pulmonary artery in renal cell carcinoma.

Anesthetic management of patients with renal cell carcinoma with tumor thrombus in the inferior vena cava (IVC) is challenging. This paper reports the experience of anesthesia management in a patient with advanced renal cell carcinoma with thrombus accumulation in the IVC, right atrium, and pulmonary artery who underwent radical nephrectomy and tumor thrombus removal assisted by cardiopulmonary bypass. The emboli, measuring approximately 3 × 6 cm in the left inferior pulmonary artery and 4 × 13 cm in the right main pulmonary artery, were removed completely. During incision of the IVC under systemic heparinization, significant blood loss occurred in the surgical field. The surgery took 724 min, and cardiopulmonary bypass took 396 min. Intraoperative blood loss was 22,000 ml. The patient was extubated 39 hours after surgery and stayed in intensive care unit for 3 days. At 1 year follow-up, the patient was in good health and leading a normal life.

Global trends in research of pseudomyxoma peritonei: a bibliometric and visualization analysis.

Objective: Pseudomyxoma peritonei (PMP) was a complex disease that had attracted increasing attention. However, there had been no bibliometric analysis of this disease so far. This study aimed to explore the current situation and frontier trend of PMP through bibliometric and visualization analysis, and to indicate new directions for future research. Methods: The original research articles and reviews related to the PMP research were downloaded from Web of Science Core Collection on September 11, 2023. CiteSpace (6.2.R4) and VOSviewer(1.6.18) were used to perform bibliometric analysis of the publications, and establish the knowledge map. The data collected was analyzed using the Online Analysis Platform of Bibliometric to evaluate the cooperation of countries in this field. Results: We identified 1449 original articles and reviews on PMP published between 1998 and 2023. The number of publications on PMP increased continuously. The United States, the United Kingdom and China were the top contributors. The most productive organization was the MedStar Washington Hospital Center. Sugarbaker, Paul H. was the most prolific author and the most cited. Keyword analysis showed that "Pseudomyxoma peritonei", "cancer", "cytoreductive surgery", and "hyperthermic intraperitoneal chemotherapy" were the most common keywords. The earliest and latest used keywords were "mucinous tumors" and "impact", respectively. "classification", "cytoreductive surgery", "appendiceal" were the top 3 strongest citation bursts. The reference "Carr NJ, 2016, AM J SURG PATHOL" had the highest co-citations. Conclusion: This bibliometric analysis showed an increasing trend in literature related to PMP. The research trends and hotspots identified in this study could guide the future research directions in this field, in order to promote the development of PMP.

Feasibility study of intubation in lateral position using Viva-sight double-lumen tube combined with video laryngoscope in patients undergoing pulmonary lobectomy.

BACKGROUND: Double-lumen tube (DLT) intubation in lateral decubitus position is rarely reported. We designed this study to evaluate the feasibility of VivaSight double-lumen tube (VDLT) intubation assisted by video laryngoscope in lateral decubitus patients. METHODS: Patients undergoing elective video-assisted thoracoscopic surgery (VATS) for lung lobectomy were assessed for eligibility between January 2022 and December, 2022. Eligible patients were randomly allocated into supine intubation group (group S) and lateral intubation group (group L) by a computer-generated table of random numbers. The prime objective was to observe whether the success rate of VDLT intubation in lateral position with the aid of video laryngoscope was not inferior to that in supine position. RESULTS: A total of 116 patients were assessed, and 88 eligible patients were randomly divided into group L (n = 44) and group S (n = 44). The success rate of the first attempt intubation in the L group was 90.5%, lower than that of S group (97.7%), but there was no statistical difference (p > 0.05). Patients in both groups were intubated with VDLT for no more than 2 attempts. The mean intubation time was 91.98 ± 26.70 s in L group, and 81.39 ± 34.35 s in S group (p > 0.05). The incidence of the capsular malposition in the group L was 4.8%, less than 36.4% of group S (p < 0.001). After 24 h of follow-up, it showed a higher incidence of sore throat in group S, compared to that in group L (p = 0.009). CONCLUSION: Our study shows the comprehensive success rate of intubation in lateral decubitus position with VDLT assisted by video laryngoscope is not inferior to that in supine position, with less risk of intraoperative tube malposition and postoperative sore throat. TRIAL REGISTRATION: Chinese Clinical Trail Register (ChiCTR2200062989).

Accuracy and efficiency of robotic dental implant surgery with different human-robot interactions: An in vitro study.

OBJECTIVES: This study aims to compare the surgical efficiency (preparation and operation time) and accuracy of implant placement between robots with different human-robot interactions. METHODS: The implant robots were divided into three groups: semi-active robot (SR), active robot (AR) and passive robot (PR). Each robot placed two implants (#31 and #36) on a phantom, practising 10 times. The surgical efficiency and accuracy of implant placement were then evaluated. RESULTS: Sixty implants were placed in 30 phantoms. The mean preparation times for the AR, PR and SR groups were 3.85 ± 0.17 min, 2.14 ± 0.06 mins and 1.65 ± 0.19 mins, respectively. The mean operation time of the PR group (3.76 ± 0.59 min) was shorter that of than the AR (4.89 ± 0.70 mins) and SR (4.59 ± 0.56 min) groups (all P < 0.001). The operation time of the AR group in the anterior region (4.47 ± 0.31 min) was longer than that of the SR group (4.07 ± 0.10 min) (P = 0.007). The mean coronal, apical and axial deviations of the PR group (0.40 ± 0.12 mm, 0.49 ± 0.13 mm, 0.96 ± 0.22°) were higher than those of the AR (0.23 ± 0.11 mm, 0.24 ± 0.11 mm, 0.54 ± 0.20 °) (all P < 0.001) and SR (0.31 ± 0.10 mm, 0.36 ± 0.12 mm, 0.43 ± 0.14 °) groups (P = 0.044, P = 0.002, and P < 0.001, respectively). CONCLUSIONS: Human-robot interactions affect the efficiency of implant surgery. Active and semi-active robots show comparable implant accuracy. However, the implants placed by the passive robot show higher deviations. CLINICAL SIGNIFICANCE: This in vitro study preliminarily demonstrates that implant placement is accurate when using implant robots with different human-robot interactions. However, different human-robot interactions have variable surgical efficiencies.

Adductor Canal Block Combined with General Analgesia for Patients with Recurrent Patellar Dislocation Undergoing "3-in-1" Procedure Surgery: A Prospective Randomized Controlled Trial.

OBJECTIVE: Patellar dislocation is a common injury in sports medicine. While surgical treatment is an important option, pain is severe after surgery. This study compared the analgesic effect and early rehabilitation quality between adductor canal block combined with general analgesia (ACB + GA) and single general analgesia (SGA) after recurrent patellar dislocation (RPD) for "3-in-1" procedure surgery. METHODS: From July 2018 to January 2020, a prospective randomized controlled trial was conducted in analgesia management after RPD for "3-in-1" procedure surgery. The 40 patients in the experimental group received ACB (0.3% ropivacaine 30 mL) + GA, while the 38 patients in the control group received SGA. Patients in both groups received "3-in-1" procedure surgery, standardized anesthesia, and analgesia during hospitalization. The outcomes included the visual analog scale (VAS), quadriceps strength, Inpatient Satisfaction Questionnaire (IPSQ), Lysholm scores, and Kujala scores. Total rescue analgesic consumption and adverse events were also recorded. One-way analysis of variance (ANOVA) was used to compare continuous variables between groups and chi-square or Fisher's exact tests were used to compare count data. Nonparametric Kruskal-Wallis H tests evaluated ranked data. RESULTS: No significant differences in resting VAS scores were observed at 8, 12, and 24 h postoperatively. However, the flexion and moving VAS scores of the ACB + GA group were significantly lower than those of the SGA group (p < 0.05). Meanwhile, the first triggering of rescue analgesics was advanced in the SGA group (p < 0.0001), and the dose of opioid analgesics was significantly higher (p < 0.0001). The quadriceps strength of the ACB + GA group was higher than that of the SGA group at 8 h postoperatively. The IPSQ of the ACB + GA group was significantly higher 24 h postoperatively. We observed no significant differences in Lysholm and Kujala scores between the two groups at 3 months after surgery. CONCLUSIONS: Early analgesia management of ACB + GA showed excellent analgesia effectiveness and a positive hospitalization experience for RPD patients undergoing "3-in-1" procedure surgery. Moreover, this management was good for early rehabilitation.

The effect of implant surgery experience on the learning curve of a dynamic navigation system: an in vitro study.

BACKGROUND: Dynamic navigation systems have a broad application prospect in digital implanting field. This study aimed to explore and compare the dynamic navigation system learning curve of dentists with different implant surgery experience through dental models. METHODS: The nine participants from the same hospital were divided equally into three groups. Group 1 (G1) and Group 2 (G2) were dentists who had more than 5 years of implant surgery experience. G1 also had more than 3 years of experience with dynamic navigation, while G2 had no experience with dynamic navigation. Group 3 (G3) consisted of dentists with no implant surgery experience and no experience with dynamic navigation. Each participant sequentially placed two implants (31 and 36) on dental models according to four practice courses (1-3, 4-6, 7-9, 10-12 exercises). Each dentist completed 1-3, 4-6 exercises in one day, and then 7-9 and 10-12 exercises 7 ± 1 days later. The preparation time, surgery time and related implant accuracy were analyzed. RESULTS: Three groups placed 216 implants in four practice courses. The regressions for preparation time (F = 10.294, R2 = 0.284), coronal deviation (F = 4.117, R2 = 0.071), apical deviation (F = 13.016, R2 = 0.194) and axial deviation (F = 30.736, R2 = 0.363) were statistically significant in G2. The regressions for preparation time (F = 9.544, R2 = 0.269), surgery time (F = 45.032, R2 = 0.455), apical deviation (F = 4.295, R2 = 0.074) and axial deviation (F = 21.656, R2 = 0.286) were statistically significant in G3. Regarding preparation and surgery time, differences were found between G1 and G3, G2 and G3. Regarding implant accuracy, differences were found in the first two practice courses between G1 and G3. CONCLUSIONS: The operation process of dynamic navigation system is relatively simple and easy to use. The linear regression analysis showed there is a dynamic navigation learning curve for dentists with or without implant experience and the learning curve of surgery time for dentists with implant experience fluctuates. However, dentists with implant experience learn more efficiently and have a shorter learning curve.

Identification and validation of autophagy-related genes during osteogenic differentiation of bone marrow mesenchymal stem cells.

Objectives: Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is an essential stage in bone formation. Autophagy plays a pivotal role in the self-renewal potential and pluripotency of stem cells. This study aimed to explore the function of autophagy-related genes during osteogenic differentiation of BMSCs. Materials and Methods: The differentially expressed autophagy-related genes (ARGs) were obtained from the GEO and HADb databases. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. The PPI and hub gene mining networks were constructed using the STRING database and Cytoscape. Finally, the RT-qPCR was conducted to validate the expression level of ARGs in BMSCs. Results: Thirty-seven differentially expressed ARGs were finally obtained, including 12 upregulated and 25 downregulated genes. GO and KEGG enrichment analysis showed that most of these genes were enriched in apoptosis and autophagy. The PPI network revealed strong interactions between differentially expressed ARGs. The expression level of differentially expressed ARGs tested by RT-qPCR showed 6 upregulated ARGs, including FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, and 4 downregulated ARGs, including MAPK8IP1, NRG1, VEGFA, and ITGA6 were consistent with the expression of high-throughput sequencing data. Conclusion: We identified 37 ARGs during osteogenic differentiation using bioinformatics analysis. FOXO1, MAP1LC3C, CTSB, FOXO3, CALCOCO2, FKBP1A, MAPK8IP1, NRG1, VEGFA, and ITGA6 may regulate osteogenic differentiation of hBMSCs by involving autophagy pathway. This study provides new insight into the osteogenic differentiation of hBMSCs and may be available in developing therapeutic strategies for maxillofacial bone defects.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial.

BACKGROUND: High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE: The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION: This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES: The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS: A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/µL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION: STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION: This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Expression of cartilage oligomeric matrix protein (COMP) associates with capsular invasion in salivary gland pleomorphic adenoma.

BACKGROUND: Accumulating evidence shows that pleomorphic adenoma (PA) exhibits a unique capsular invasion and with a crucial role in recurrence. This study was designed to explore RNA expression profiles in salivary gland PA in an attempt to further analyse genes associate with capsule invasion. METHODS: We evaluated the expression profiles of 4 salivary gland PA patients by RNA-sequencing. The principal functions of the differentially expressed mRNAs (DEGs) were explored using GO and KEGG analysis. Then, RT-qPCR and correlation analyses were performed to verify the candidate DEGs in 59 PA patients, and immunohistochemical examinations were conducted to validate candidate DEGs. Finally, the COMP-related genes were screened using correlation and biological pathway enrichment analysis, and further validated by RT-qPCR. RESULTS: A total of 974 DEGs were significantly upregulated, and 1464 were downregulated (fold change ≥2.0; p < 0.05). Based on GO and KEGG analyses, extracellular matrix organization and the PI3K-Akt signalling pathway might play pivotal roles in the tumorigenesis of PA. 40 DEGs were screened and validated by RT-qPCR, 11 upregulated and 5 downregulated DEGs were consistent with the sequencing results. Cartilage oligomeric matrix protein (COMP) was identified to have a significant correlation with the capsular invasion of PA and expression of COMP in patients with invasive capsular PA was significantly stronger than PA. Finally, further results could reveal that 5 highest scoring genes were screened as hub genes for COMP. CONCLUSIONS: These findings suggested that COMP may be a prognostic target for PA and might contribute to its capsular invasion.

Anesthetic management for cytoreductive surgery of pseudomyxoma peritonei with high intra-abdominal pressure: A case report.

Anesthetic management for patients of pseudomyxoma peritonei (PMP) is challenging. This case report describes a patient of PMP with high intra-abdominal pressure. Intubation was performed in lateral position; the intraabdominal pressure was relieved slowly to prevent significant hemodynamic changes. Additionally, positive pressure ventilation was performed to reduce the risk of re-expansion pulmonary edema. During the operation, transfusion and infusion therapy was performed with target-mediated fluid therapy according to stroke volume variation (SVV) and cardiac index (CI) and blood gas analysis.

The Effects of Titanium Surfaces Modified with an Antimicrobial Peptide GL13K by Silanization on Polarization, Anti-Inflammatory, and Proinflammatory Properties of Macrophages.

The polarization of macrophages and its anti-inflammatory and proinflammatory properties play a significant role in host response after implant placement to determine the outcome of osseointegration and long-term survival. In the previous study, we immobilized an antimicrobial peptide, GL13K, onto titanium surfaces to provide immune regulation property. In the herein presented study, we aimed at investigating whether GL13K immobilized titanium surface could improve osteogenesis and reduce the inflammatory reaction around the biomaterials by altering macrophage response. We evaluated the cell proliferation of the different phenotypes of macrophages seeded in GL13K-coated titanium surface, which indicated an inhibition of M1 macrophages and a good cytocompatibility to M2 macrophages. Then, we measured the inflammatory and anti-inflammatory activity of the M1 and M2 macrophages seeded on the GL13K-coated titanium surfaces. The results of the enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction showed that the group with the GL13K modified surface had a downregulation in the expression level of the tumor necrosis factor-α and interleukin-1ß in M1 macrophages and an upregulation of IL-10 and transforming growth factor-ß3 (TGF-ß3) levels in M2 macrophages. This study demonstrated that the GL13K modified titanium surfaces can regulate macrophages' polarization and the expression of inflammatory and anti-inflammatory effects, reducing the effects of the inflammatory process, which may promote the process of bone regeneration and osseointegration.

Adductor canal block is similar to femoral nerve block for the quality of rehabilitation after arthroscopic partial meniscectomy.

PURPOSE: Adductor canal block (ACB) provides postoperative pain relief as effectively as femoral nerve block (FNB) does, and it preserves the strength of the quadriceps femoris. However, its effect on rehabilitation after arthroscopic partial meniscectomy has not been reported. The purpose of this study was to determine the effect of pre-operative ACB and FNB on the quality of rehabilitation after arthroscopic partial meniscectomy. METHODS: A total of 150 patients undergoing arthroscopic partial meniscectomy were randomly allocated to the FNB group (receiving 0.3% ropivacaine 30 ml at the thighroot-femoral nerve), the ACB group (receiving 0.3% ropivacaine 30 ml at mid-thigh adductor canal), or the control group. The primary outcome was the Hospital for Special Surgery (HSS) knee score on the 30th postoperative day. RESULTS: The HSS knee score of the ACB group on the 30th day after the operation was significantly higher than those of the FNB and control groups (88.6 ± 5.3 vs. 85.3 ± 6.9 and 81.2 ± 5.9, respectively; P < 0.05). Both the ACB and FNB groups showed excellent rehabilitation, indicating similar rehabilitation quality for both treatments. CONCLUSION: ACB is similar to FNB concerning the quality of rehabilitation and pain relief after arthroscopic partial meniscectomy, while ACB has little effect on the strength of the quadriceps femoris. LEVEL OF EVIDENCE: I TRIAL REGISTRATAION: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INC-16008346).

Inhibition of Galectin-3 Alleviates Cigarette Smoke Extract-Induced Autophagy and Dysfunction in Endothelial Progenitor Cells.

Endothelial progenitor cells (EPCs) have the potential to repair damaged blood vessels and promote angiogenesis. Smoking, an important risk factor for cardiovascular diseases, is associated with impaired functions of EPCs. However, the underlying mechanisms remain unclear. The aim of the study was to investigate the effects of cigarette smoke extract (CSE) on autophagy and dysfunction of EPCs and the involvement of galectin-3 in its effects. EPCs were treated with 8% CSE for 24 h (without affecting cell viability). EPC functions were assessed by tube formation and migration capacity and intracellular ROS and eNOS expression. Autophagy was assessed by autophagic protein expression by Western blotting and immunofluorescence microscopy and autophagosome accumulation by transmission electron microscopy. Galectin-3 expression was measured by real-time PCR, Western blotting, and immunofluorescence microscopy, while phospho-AMPK and phospho-mTOR were measured by Western blotting. EPCs were transfected by shRNA-Gal-3 or shRNA-NC before treatment with CSE to examine the effects of galectin-3 on CSE-induced autophagy and dysfunction of EPCs. CSE-treated EPCs showed decreased tube formation and migration ability and eNOS expression but increased oxidative stress. CSE also induced autophagy which was characterized by a decrease in p62 protein, an increase in LC3B-II/I ratio, and accumulation of autophagosomes. CSE upregulated galectin-3 expression on EPCs. Inhibition of galectin-3 abrogated CSE-induced autophagy and dysfunction of EPCs. CSE activated phospho-AMPK and inhibited phospho-mTOR, and inhibition of galectin-3 abolished CSE's effect on activating phospho-AMPK and inhibiting phospho-mTOR. In conclusion, our results suggest that galectin-3 mediates CSE-induced EPC autophagy and dysfunction, likely via the AMPK/mTOR signaling pathway.

Protective effect of hydrogen sulfide on monocrotaline­induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition.

Endothelial­to­mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H2S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague­Dawley rats (10 weeks old) received a single dose of monocrotaline (MCT; i.p., 60 mg/kg) and were randomly treated with NaHS [an H2S donor; intraperitoneal (i.p.) 1 mg/kg/day], DL­propagylglycine (an inhibitor of H2S synthesis; PAG; i.p., 10 mg/kg/day) or saline, 7 days after MCT injection. Rats were sacrificed 21 days after MCT injection. A selection of human pulmonary artery endothelial cells (HPAECs) were pretreated with NaHS or saline and stimulated with transforming growth factor (TGF)­ß1 (10 ng/ml), and the other HPAECs were transfected with a cystathionine γ­lyase (CSE, an H2S synthesizing enzyme) plasmid and subsequently stimulated with TGF­ß1. NaHS was indicated to inhibit EndMT and PAH progression by inhibiting the induction of the nuclear factor (NF)­κB­Snail pathway. In contrast, the depletion of H2S formation by PAG exacerbated EndMT and PAH by activating NF­κB­Snail molecules. In HPAECs, NaHS dose­dependently inhibited TGF­ß1­induced EndMT and the activation of the NF­κB­Snail pathway. Transfection with a CSE plasmid significantly repressed TGF­ß1­induced expression of the mesenchymal marker and upregulated the expression of the endothelial marker, which was accompanied by the suppression of the NF­κB­Snail pathway. The inhibitory effect of CSE overexpression on TGF­ß1­induced EndMT was significantly reversed by pretreatment with PAG. In conclusion, the current study provides novel information elucidating the beneficial effect of H2S on PAH through inhibiting the induction of the NF­κB­Snail pathway and the subsequent process of EndMT in pulmonary arteries.

Propanol-Triggered Luminescence for Rapid Screening of Crystal Facets in Noble Metal.

The rapid and effective recognition techniques for crystal facets in noble metal nanocrystals (NCs) are highly desirable in evaluation of their catalytic performances. Herein, it was found that the variation trend of cataluminescence (CTL) intensity in the presence of propanol was proportional to the crystal facets index change of LDH-supported Pd@Au NCs. The mechanism investigation for the propanol-triggered CTL on the surface of layered double hydroxide (LDH)-supported Pd@Au NCs revealed that the abundant negative charge in the high-index facets of LDH-supported Pd@Au NCs facilitated electron transfer between NCs and volatile propanol, resulting in acceleration of the CTL reactions. Accordingly, the propanol-triggered CTL can be as an indicator for rapid screening of crystal facets in NCs. Its universality had further been verified by screening crystal facets in LDH-supported Pd NCs. The crystal facets detected by propanol CTL probe were well-matched with those obtained by conventional high-resolution transmission electron microscope. The proposed CTL strategy exhibits some advantages, such as convenient operation, rapid response, long-term stability, and low cost. And it is expected crystal facets of other kinds of NCs could be screened by replaceable CTL probe.

Challenges in the surgical treatment of undiagnosed functional paragangliomas: A case report.

INTRODUCTION: Paragangliomas (PGs) or extra-adrenal pheochromocytomas are rare neuroendocrine neoplasms of ubiquitous distribution. Those that produce excess catecholamine are categorized as functional, and those that do not are categorized as nonfunctional. Although modern medical technology is becoming more widespread, there are still substantial risks of misdiagnosis or missed diagnosis of PGs. CASE PRESENTATION: A 38-year-old woman who lived in an autonomous region of inner Mongolia presented complaining of having experienced coughing for approximately the past month. Chest computed tomography (CT) and magnetic resonance imaging (MRI) revealed a lesion on the right side of thoracic vertebra 5-8 of approximately 66 mm × 54 mm, and it was deemed to be a mediastinal tumor that required surgical treatment. The patient exhibited severe hemodynamic instability during the operation, resulting in substantial challenges and risks with regard to anesthesia management. CONCLUSION: When a patient is suspected having PG, whether the surgery should be continued or not depends on their overall condition and whether hemodynamic fluctuation can be controlled to within the normal range. Both are factors that should be considered during intraoperative management. Communication between the surgeon and anesthesiologist is necessary, in order to accurately assess the risks associated with the operation. The combination of central venous pressure and the Flotrac/Vigileo system may provide precise guidance for complementary liquid therapy and reduce cardiopulmonary complications. After the operation, hemodynamic changes should be monitored continuously in the intensive care unit, and vasoactive drugs are required to avoid postoperative hypotension. Dramatic hemodynamic changes are certainly a challenge for patients and anesthesiologists, regardless of their origin, and sufficient attention should be paid to avoid serious consequences.

Regulation of Folate-Mediated One-Carbon Metabolism by Glycine N-Methyltransferase (GNMT) and Methylenetetrahydrofolate Reductase (MTHFR).

Folate-mediated one-carbon metabolism is an important therapeutic target of human diseases. We extensively investigated how gene-nutrient interactions may modulate human cancer risk in 2 major folate metabolic genes, MTHFR and GNMT. The biochemical impacts of MTHFR and GNMT on methyl group supply, global DNA methylation, nucleotide biosynthesis, DNA damage, and partitioning of the folate dependent 1-carbon group were carefully studied. The distinct model systems used included: EB virus-transformed lymphoblasts expressing human MTHFR polymorphic genotypes; liver-derived GNMT-null cell-lines with and without GNMT overexpression; and HepG2 cells with stabilized inhibition of MTHFR using shRNA, GNMT wildtype, heterozygotous (GNMT(het)) and knockout (GNMT(nul)) mice. We discovered that the MTHFR TT genotype significantly reduces folate-dependent remethylation under folate restriction, but it assists purine synthesis when folate is adequate. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in human hematological malignancies. GNMT affects transmethylation kinetics and S-adenosylmethionine (adoMet) synthesis, and facilitates the conservation of methyl groups by limiting homocysteine remethylation fluxes. Restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. The systematic series of studies gives new insights into the underlying mechanisms by which MTHFR and GNMT may participate in human tumor prevention.

A novel role of the tumor suppressor GNMT in cellular defense against DNA damage.

Glycine N-methyltransferase (GNMT) is a folate binding protein commonly diminished in human hepatoma yet its role in tumor development remains to be established. GNMT binds to methylfolate but is also inhibited by it; how such interactions affect human carcinogenesis is unclear. We postulated that GNMT plays a role in folate-dependent methyl group homeostasis and helps maintain genome integrity by promoting nucleotide biosynthesis and DNA repair. To test the hypothesis, GNMT was over-expressed in GNMT-null cell lines cultured in conditions of folate abundance or restriction. The partitioning of folate dependent 1-carbon groups was investigated using stable isotopic tracers and GC/MS. DNA damage was assessed as uracil content in cell models, as well as in Gnmt wildtype (Gnmt(+/+)), heterozygote (Gnmt(+/-)) and knockout (Gnmt(-/-)) mice under folate deplete, replete, or supplementation conditions. Our study demonstrated that GMMT 1) supports methylene-folate dependent pyrimidine synthesis; 2) supports formylfolate dependent purine syntheses; 3) minimizes uracil incorporation into DNA when cells and animals were exposed to folate depletion; 4) translocates into nuclei during prolonged folate depletion. In conclusion, loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. To our best knowledge, the role of GNMT in folate dependent 1-carbon transfer in nucleotide biosynthesis has never been investigated. The present study gives new insights into the underlying mechanism by which GNMT can participate in tumor prevention/suppression in humans.

Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis.

Varicocele, a cause of male infertility, occurs in nearly 40% of infertile males. It has been postulated that varicoceles may cause sperm DNA damage. Sperm DNA integrity has been recognized as one of the important determinants of normal fertilization and embryo growth in natural and assisted conception. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. Data were analysed using RevMan software. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). In conclusion, there is increased sperm DNA damage in patients with varicoceles and varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding. A varicocele is an important cause of male infertility and occurs in nearly 40% of infertile males. The recent understanding of the effect of varicoceles in male reproduction has led some researchers to postulate varicoceles as the possible cause of sperm DNA damage. Eighty-three human studies were identified after an extensive literature search involving the role of varicoceles in sperm DNA damage. Of the 83 studies, 12 were selected that measured similar types of reactive sperm DNA damage by a similar method. Seven studies determined the damage of sperm DNA in varicocele-associated patients and six studies evaluated the efficacy of varicocelectomy. One study was a duplicate because both outcomes were included. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients with varicoceles have significantly higher sperm DNA damage than controls, with a mean difference of 9.84% (95% CI 9.19 to 10.49; P<0.00001). A varicocelectomy can improve sperm DNA integrity, with a mean difference of -3.37% (95% CI -4.09 to -2.65; P<0.00001). Based on the results, it can be concluded that there is increased sperm DNA damage in patients with varicoceles and that varicocelectomy may be a possible treatment; however, more studies with appropriate controls are needed to confirm this finding.