Copper-Catalyzed Sulfonylation/Cyclization of Pent-4-ynamides toward Sulfonyl-Functionalized Pyrrol-2-ones.

A domino sulfonylation/intramolecular C-N coupling/dehydrogenation reaction was realized between pent-4-ynamides and sulfonyl chlorides by catalysis of Cu(acac)2 and 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene. The reaction provides a convenient approach to sulfonyl-functionalized pyrrol-2-ones. This method can also be applied to the synthesis of 3-alkylidene isoindolinones from 2-ethynyl-benzamides.

Effect of sevoflurane anesthesia to neonatal rat hippocampus by RNA-seq.

BACKGROUND: Sevoflurane is an inhalational anesthetic for the induction and maintenance of general anesthesia in pediatric surgery. However, few studies have paid attention to the multiple organ toxicity and the mechanism behind it. METHODS: Inhalation anesthesia neonatal rat model were realized by exposing to 3.5% sevoflurane. RNA-seq was performed to find out how inhalation anesthesia affects the lung, cerebral cortex, hippocampus, and heart. Validation of RNA-seq results by QPCR after animal model establishment. Tunel assay detects cell apoptosis in each group. CCK-8, cell apoptosis assay and western blot assay validation of the role of siRNA-Bckdhb in the action of sevoflurane on rat hippocampal neuronal cells. RESULTS: There are significant differences between different groups, especially the hippocampus and cerebral cortex. Bckdhb was significantly up-regulated in the hippocampus with sevoflurane-treated. Pathway analysis revealed several abundant pathways related to DEGs, e.g., protein digestion and absorption and PI3K-Akt signaling pathway. A series of cellular and animal experiments showed that siRNA-Bckdhb can inhibit the reduction of cellular activity caused by sevoflurane. CONCLUSION: Bckdhb interference experiments indicated that sevoflurane induces hippocampal neuronal cells apoptosis by regulating Bckdhb expression. Our study provided new insights into the molecular mechanism of sevoflurane-induced brain damage in pediatrics.

Programmable 4D Printing of Photoactive Shape Memory Composite Structures.

4D printing is an advanced manufacturing technology combining additive manufacturing with smart materials. Based on light-active shape memory composites, smart medical structures with remote control capability, therapeutic function, and biocompatibility are hopefully fabricated by 4D printing. Here, a multifunctional composite with good mechanical properties, biocompatibility, and light-active shape memory performance is prepared by incorporating gold nanoparticles into a shape memory polyurethane matrix. The composites demonstrate a rapid and stable light-thermal effect, which can achieve localized and controlled breast tumor ablation, providing an approach to hyperthermia treatment for cancer cells. By directly bioprinting the composite melt, a series of 4D-printed structures are manufactured accurately in a convenient, clean, and safe way, which show a fast autonomous light-driven shape recovery process. The examples of a 4D-printed soft tissue scaffold and intraluminal scaffold can expand from a conveniently insertional shape to an expanded shape under light exposure. The proposed strategies provide great inspiration for customized multifunctional light-thermal therapeutic structures for minimally invasive treatment.

Determinants of Complex Regional Pain Syndrome Type I among Radial Head Fracture Patients with Unilateral Arthroplasty.

OBJECTIVE: This study aims to assess the proportions of complex regional pain syndrome type I (CRPS I) in radial head fracture patients undergoing unilateral arthroplasty and to explore associated factors. METHODS: This is a prospective observational study. From March 2016 to May 2019, a total of 221 adult patients with radial head fracture patients were included in consecutive studies and completed the 1-year follow-up. All patients were treated by unilateral arthroplasty. At each follow-up visit, the visual analogue scale was used to measure patients' pain level. Occurrence of CRPS I, which was diagnosed by Budapest criteria, was the main outcome collected at baseline and the 1-, 3-, 6-, and 9-month follow-ups. The baseline data were collected before surgery and included demographic and clinical data. Independent t-tests and χ2 tests were used as univariate analyses to compare the baseline data of patients with and without CRPS I. Multivariate analysis (Backword-Wald) was used to identify factors independently associated with CRPS I. RESULTS: The proportion of CRPS I cases among radial head fracture patients undergoing unilateral arthroplasty was 11% (n = 24). A total of 19 (79%) patients were diagnosed with CRPS I within 1 month after surgery. Multivariable logistic regression analysis revealed that female gender (odds ratios [OR]: 1.537; 95% confidence interval [CI]: 1.138-2.072), age younger than 60 years (OR: 1.682; 95% CI: 1.246-2.267), moderate and severe Mayo Elbow Performance Score (MEPS) pain (OR: 3.229; 95% CI: 2.392-4.351) and anxiety (OR: 83.346; 95% CI: 61.752-112.320) were independently associated with CRPS I. CONCLUSIONS: This exploratory study reported that the incidence of CRPS I developing after radial head arthroplasty was 11%. Female sex, younger age, moderate and severe MEPS pain and anxiety patients seems more likely to develop CRPS I.

Age-related visual impairments and retinal ganglion cells axonal degeneration in a mouse model harboring OPTN (E50K) mutation.

Retinal ganglion cells (RGCs) axons are the signal carriers of visual information between retina and brain. Therefore, they play one of the important roles affected in many optic neurodegenerative diseases like glaucoma. Among the genetic risks associated with glaucoma, the E50K mutation in the Optineurin (OPTN) gene are known to result in glaucoma in the absence of increased intraocular pressure (IOP), whereas the relevant pathological mechanism and neurological issues remain to be further investigated. In this study, the OPTN (E50K) mutant mouse model was established through CRISPR/Cas9-mediated genome editing, and aging-related RGCs loss and the visual dysfunction were identified. In E50K mice 16 months old, the axonal transport decreased comparing to wild-type (WT) mice at the same age. Furthermore, results of electron microscopy demonstrated significant morphological anomaly of mitochondria in RGCs axons of young E50K mice 3 months old, and these changes were aggravated with age. These indicated that the damaged mitochondria-associated dysfunction of RGCs axon should play an etiological role in glaucoma as an age-related outcome of OPTN (E50K) mutation. The findings of this study have potential implications for the targeted prevention and treatment of NTG.

Evaluation of Pericapsular Nerve Group (PENG) Block for Analgesic Effect in Elderly Patients with Femoral Neck Fracture Undergoing Hip Arthroplasty.

BACKGROUND: For evaluating pericapsular nerve group (PENG) block's analgesic effect on elderly patients suffering from femoral neck fracture undergoing hip arthroplasty to provide a basis for optimizing perioperative analgesia in hip arthroplasty. METHODS: Forty-eight patients undergoing hip arthroplasty with spinal anesthesia for femoral neck fracture in our hospital were chosen in this study. Based on the random number table method, patients were categorized into the following two groups (n = 24 per group): the hip peripheral nerve group block group (PE group) and the iliac fascia block group (FI group). The fascia iliaca compartment block was used in the FI group, whereas the pericapsular nerve group block in the PE group. When placed in the position for spinal anesthesia (T4), we measured dynamic and static visual analog scale (VAS) scores as well as analgesic satisfaction before blockade (T0), along with at 10 min (T1), 20 min (T2), and 30 min postblockade (T3). Sufentanil dosage and effective analgesic pump press number at 6 h (T5), 12 h (T6), 24 h (T7), and 48 h (T8) postoperatively were recorded. In the meantime, the development of related complications was also recorded. RESULTS: Compared with T0, patients in both groups achieved lower static VAS scores at T1-T4 (P < 0.05) and lower dynamic VAS scores at T2-T4 of the FI group (P < 0.05). Relative to the FI group, both static and dynamic VAS scores at T1-T4 were obviously lower in the PE group (P < 0.05), along with increased dynamic analgesic satisfaction (P < 0.05). Weakness of the quadriceps was observed in seven patients in the FI groups (P < 0.05). No delirium, hematoma, puncture site infection, or nerve injury occurred in either group. CONCLUSION: The pericapsular nerve group block can provide safe and effective analgesia for elderly patients during the perioperative period of hip arthroplasty, with rapid onset, good analgesic effect, high patient satisfaction, and low complication rate, and is worthy of widespread application. The trial is registered with ChiCTR2100046785.

Effect of long-term weight gain on the risk of breast cancer across women's whole adulthood as well as hormone-changed menopause stages: A systematic review and dose-response meta-analysis.

Adult weight gain is a good indicator of excess body fatness for breast cancer risk. However, little is known about the effect of weight gain during other special periods in women's lifetime. A publication search in PubMed and Embase through April 2020 was conducted. A primary meta-analysis comparing the highest and lowest category and a secondary meta-analysis based on dose-response meta-analysis were performed to calculate risk estimates with 95% confidence intervals using a random-effects model. For postmenopausal breast cancer, the relative risk for highest vs. lowest category of adult weight gain and weight gain since menopause were 1.55 and 1.59 (RR = 1.55, 95% CI: 1.40, 1.71; RR = 1.59, 95% CI: 1.23, 2.05). For per 5 kg increase in adult weight gain, the summary RR of postmenopausal breast cancer was 1.08 (RR = 1.08, 95% CI: 1.07, 1.09), which is much stronger in Asian women (RR = 1.34, 95% CI: 1.22, 1.47). There was no significant finding among premenopausal women (RR = 1.00, 95% CI: 0.83, 1.21). Same as adult weight gain, weight gain since menopause might be an equivalent predictor for postmenopausal breast cancer risk. More studies are warranted to confirm the magnitude of this association further.

Neuroprotective effects of bone marrow Sca-1+ cells against age-related retinal degeneration in OPTN E50K mice.

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1- chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1- cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1- chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1- cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.

Effect of intravenous oxycodone on the physiologic responses to extubation following general anesthesia.

BACKGROUND: Endotracheal intubation and extubation may cause undesirable hemodynamic changes. Intravenous oxycodone has recently been introduced and used for relieving hemodynamic alterations in response to intubation, but there is insufficient information regarding its application in stabilizing hemodynamics during extubation in the patients emerging from general anesthesia. METHODS: One hundred patients, who had undergone assorted laparoscopic surgeries under general anesthesia, were randomly assigned to Control group (saline injection, 50 cases) and Study group (intravenous injection of 0.08 mg/kg oxycodone immediately after completion of the surgical procedure, 50 cases). Blood pressure, heart rate, blood oxygen saturation (SpO2) as well as blood concentrations of epinephrine, norepinephrine, and cortisol were recorded or measured immediately before extubation (T0), during extubation (T1), as well as one minute (T2), 5 min (T3), and 10 min after extubation (T4). In addition, coughing and restlessness, time of eye-opening, and duration from completing surgery to extubation as well as Ramsay Sedation Scale were analyzed. RESULTS: Blood pressure and heart rate as well as blood concentrations of epinephrine, norepinephrine, and cortisol were significantly higher in the Control group compared with the Study group at the time of extubation as well as 1, 5, and 10 min after extubation (P < 0.05). When the patients emerged from general anesthesia, 70 % of the Control group had cough, which was significantly higher than that of Study group (40 %, P < 0.05). Significantly higher number of patients manifested restlessness in the Control group before (40 %) and after extubation (20 %) compared with that in the Study group (20 and 2 %, respectively, P < 0.05). In addition, patients of Control group had lower Ramsay score at extubation (1.7 ± 0.7) as well as 30 min after extubation (2.4 ± 0.9) compared to that of the patients of Study group (2.2 ± 0.9, and 3.0 ± 0.8, respectively, P = 0.003 and 0.001). CONCLUSIONS: Intravenous oxycodone attenuated alterations of hemodynamics and blood hormones associated with extubation during emergence from general anesthesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000040370 (registration date: 11-28-2020) "'retrospectively registered".

Proteomic analysis of aged and OPTN E50K retina in the development of normal tension glaucoma.

Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma. To elucidate proteomic and biochemical pathway alterations during NTG development, we established an OPTN E50K mutant mouse model through CRISPR/Cas9. Retinal proteins from resulting mice exhibiting glaucomatous phenotypes were subject to tandem mass tag-labeled quantitative proteomics and then analyzed through bioinformatics methods to characterize the molecular and functional signatures of NTG. We identified 6364 quantitative proteins in our proteomic analysis. Bioinformatics analysis revealed that OPTN E50K mice experienced protein synthesis dysregulation, age-dependent energy defects and autophagy-lysosome pathway dysfunction. Certain biological features, including amyloid deposition, RNA splicing, microglia activation and reduction of crystallin production, were similar to Alzheimer's disease. Our study is the first to describe proteomic and biochemical pathway alterations in NTG pathogenesis during disease advancement. Several proteomic signatures overlapped with retinal changes found in the ad mice model, suggesting the presence of common mechanisms between age-related degenerative disorders, as well as prospective new targets for diagnostic and therapeutic strategies.

Analgesic effect of Ropivacaine combined with Dexmedetomidine on brachial plexus block.

BACKGROUND: This randomized controlled study investigated the analgesic effect of ropivacaine in combination with dexmedetomidine versus ropivacaine alone on brachial plexus block to provide alternative anesthetic means for upper limb trauma surgery. METHODS: Totally 114 patients who received upper limb surgeries under brachial plexus block anesthesia in our hospital from February 2013 to July 2015 were enrolled. The patients were randomized to ropivacaine alone (the control group) or ropivacaine combined with dexmedetomidine (the combination group). The blocking effect on sensory and motor neurons, visual analog scale (VAS) score, heart rate (HR), mean arterial pressure (MAP), peripheral capillary oxygen saturation (SPO2) and adverse reactions were compared between the two groups. RESULTS: The time to onset of sensory and motor nerve blockade was significantly shorter in the combination group than in the control group (8.9 min vs. 12.4 min for sensation blockade; 7.5 min vs. 12.8 min for motor blockade, P < 0.05 for both comparisons), and the duration of the blockade was significantly longer in the combination group (590.2 min vs. 532.1 min, P < 0.05). There was no significant difference in VAS scores between the two groups immediately and 4 h after surgery; however, 8, 12 and 24 h after surgery, the VAS scores were all significantly lower in the combination group than the control group (2.4 vs. 3.0 for 8 h; 2.2 vs. 4.2 for 12 h, and 2.1 vs. 5.4 for 24 h, respectively, P < 0.05 for all comparisons). There was no statistical difference in HR, MAP and SPO2 between the two groups before anesthesia, but after anesthesia, the MAP and HR were significantly lower, and the SPO2 was significantly higher in the combination group than the control group (78 vs. 84 for MAP; 72 vs. 79 for HR; and 95.1 vs. 88.2 for SPO2, P < 0.05 for all comparisons). The rates of adverse reaction was significantly lower in the combination group than the control group (3.6 vs. 7.2, P < 0.05). CONCLUSION: The brachial plexus blocking effect of ropivacaine combined with dexmedetomidine was superior to that of ropivacaine alone, mainly intra-operatively and postoperatively. TRIAL REGISTRATION: Analgesic Effect of Ropivacaine Combined with Dexmedetomidine on Brachial Plexus Block, ChiCTR1800017372, retrospectively registered on July 26, 2018.

Effect of soybean protein on blood pressure in postmenopausal women: a meta-analysis of randomized controlled trials.

The effect of soybean protein on blood pressure (BP) in postmenopausal women is controversial, so we aimed to conduct a systematic review and a meta-analysis of published randomized controlled trials (RCTs) to investigate whether supplementation with soy protein improves their blood pressure. PubMed and Embase were searched up to February 2016. Weighted mean differences were calculated for net changes in BP by using fixed-effect or random-effect models. Subgroup and meta-regression analyses were performed to clarify heterogeneity among the trials. A total of twelve trials (1551 postmenopausal women participants) were included in the present meta-analysis. The overall pooled estimates of the effect of soy protein indicated a significant effect on systolic blood pressure (SBP) (mean difference: -3.03 mmHg; 95% CI: -5.03, -1.02; P = 0.003) and diastolic blood pressure (DBP) (mean difference: -0.71 mmHg; 95% CI: -1.26, -0.16; P = 0.012). Subgroup analyses further demonstrated that soy protein intake ≥25 g d-1 significantly reduced BP, and the mean difference in SBP and DBP was -4.62 mmHg (95% CI: -8.42, -0.81; P = 0.04) and -1.63 mmHg (95% CI: -2.85, -0.41; P = 0.009), respectively. Soy isoflavone intake ≥100 mg d-1 had a better reduction effect both in SBP (-5.47 mmHg; 95% CI: -8.42, -2.51; P = 0.00) and DBP (-2.03 mmHg; 95% CI: -3.35, -0.72; P = 0.002). However, soy protein intake <25 g d-1 or soy isoflavone intake <100 mg d-1 had no such effects (P > 0.05). This meta-analysis suggests that ingestion of ≥25 g soy protein per day has BP-lowering effects, and the improvements in BP may be due to the isoflavones component of soy protein. More high-quality RCTs need to be carried out to confirm the present findings.