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The polysaccharide composition of dried bulbs of Orchis mascula (L.) L. is reported. The obtained polysaccharides were studied as sulfate derivatives, were called SP-S, and were purified by ion-exchange chromatography over a column of DEAE 650M to afford four fractions. Homogeneous polysaccharides were obtained by purifying these fractions using a column of Sephadex G-150. The chemical characteristics were studied. The antioxidant properties of these fractions were determined.

BACKGROUND Cardiac embolism is a common cause of ischemic stroke in young adults. Neurological complications associated with atrial myxoma most frequently include cerebral infarct due to embolus. Early complete resection of giant cardiac myxoma is the key to its treatment and prevention of stroke recurrence. CASE SUMMARY A 42-year-old, previously healthy woman was admitted to the hospital with sudden-onset inability to speak and right-sided hemiplegia. While sweeping the floor 2 h prior to hospital admission, the patient developed sudden inability to express herself or understand what others were saying, accompanied by dyskinesia of the right limb, inability to walk or hold objects, and involuntary choreiform movements of the left upper limb. The patient was diagnosed with cerebral embolism and cardiac myxoma, complicated by left middle cerebral artery occlusion. The acute stroke was treated with intravenous thrombolytic therapy and arterial embolectomy as a bridging therapy to open resection of left atrial cardiac myxoma. The patient condition improved remarkably following initial thrombolysis and embolectomy and subsequently underwent emergency open resection of the atrial cardiac myxoma. She had no recurrence during 1-year follow-up. CONCLUSION Strong consideration should be given to urgent intravenous thrombolysis (rt-PA, alteplase) in young adult stroke patients at the time of hospital admission. The present case demonstrated a highly successful outcome that combined thrombolysis and arterial embolus retrieval as a bridge to early complete resection of a giant cardiac myxoma for both stroke treatment and recurrence prevention.

Objectives Patients with psychiatric disorders have an increased risk of cardiovascular pathologies. A bidirectional feedback model between the brain and heart exists widely in both psychotic and nonpsychotic disorders. The aim of this study was to compare heart rate variability (HRV) and pulse wave velocity (PWV) functions between patients with psychotic and nonpsychotic disorders and to investigate whether subgroups defined by HRV and PWV features improve the transdiagnostic psychopathology of psychiatric classification. Methods In total, 3448 consecutive patients who visited psychiatric or psychological health services with psychotic (N = 1839) and nonpsychotic disorders (N = 1609) and were drug-free for at least 2 weeks were selected. HRV and PWV indicators were measured via finger photoplethysmography during a 5-minute period of rest. Canonical variates were generated through HRV and PWV indicators by canonical correlation analysis (CCA). Results All HRV indicators but none of the PWV indicators were significantly reduced in the psychotic group relative to those in the nonpsychotic group. After adjusting for age, gender, and body mass index, many indices of HRV were significantly reduced in the psychotic group compared with those in the nonpsychotic group. CCA analysis revealed 2 subgroups defined by distinct and relatively homogeneous patterns along HRV and PWV dimensions and comprising 19.0% (subgroup 1, n = 655) and 80.9% (subgroup 2, n = 2781) of the sample, each with distinctive features of HRV and PWV functions. Conclusions HRV functions are significantly impaired among psychiatric patients, especially in those with psychosis. Our results highlight important subgroups of psychiatric patients that have distinct features of HRV and PWV which transcend current diagnostic boundaries.

BACKGROUND Addiction to online games is not uncommon. The patients usually refuse to take medications and present with affective symptoms such as anxiety, depression and negative coping styles. Psychological intervention based on positive psychology is a promising treatment for such patients. AIM To evaluate the effect of positive psychological intervention on anxiety, depression and coping in people addicted to online games. METHODS This self-controlled study included 89 people addicted to online games, who received treatment at Hangzhou Seventh People’s Hospital, Hangzhou, China in 2019. The Hamilton Anxiety Scale, Hamilton Depression Scale and Trait Coping Style Questionnaire were administered to evaluate the anxiety, depression and coping style among these people. Psychological intervention based on positive psychology was provided for 6 wk followed by another evaluation. The results were compared against those from the previous evaluation. RESULTS After 6 wk of psychological intervention, 89 people achieved a significant improvement in the Hamilton Anxiety Scale and Hamilton Depression Scale-24 scales. The score for positive coping style in Trait Coping Style Questionnaire was significantly improved, while that of the negative coping style decreased significantly (P < 0.05). CONCLUSION Psychological intervention based on positive psychology alleviated affective symptoms, such as anxiety and depression, in subjects addicted to online games. Psychological intervention corrected negative coping style, thereby improving mental health.

Tsaokols A (1) and B (2), two complicated flavanol-monoterpenoid hybrids, were isolated from the dried fruits of Amomum tsao-ko under the guidance of LCMS and bioassay. Their structures were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 shared a flavanol backbone fused with 5/7 and 5/6 bicyclic monoterpenoid scaffolds, which were biogenetically condensed by Michael addition and acetalization. Compounds 1 and 2 exhibited significant α-glucosidase inhibitory activity with IC50 values of 18.8 and 38.6 μmol/L (acarbose, IC50 = 213 μmol/L). Docking study supported the strong interactions of 1 and 2 bonding with enzyme by mainly hydrophobic and hydrogen-bond effects. Compounds 1 and 2 could be fast distinguished by the diagnostic ions at m/z 289 and 313 in negative MS2 experiments.

Sericin, a silk protein, has a high potential for use as an extracellular matrix in tissue engineering applications. In this study, novel gelatin (GEL) and silk sericin (SS) were incorporated with a polyvinyl alcohol) PVA hydrogel nanocomposite (GEL-SS-PVA) scaffold that can be applied to repair cartilage. Glutaraldehyde was used as a cross-linking agent, with hydrochloric acid acting as an initiator. The microstructure characteristics of the obtained GEL-SS and GEL-SS-PVA scaffolds were also examined using FTIR and XRD spectra and their enhanced thermal stability was assessed by TGA. The blended GEL-SS and GEL-SS-PVA scaffolds were confirmed by SEM analysis to be highly porous with optimum pore sizes of 172 and 58 µm, respectively. Smaller pore sizes and improved uniformity were observed as the concentration of PVA in the GEL-SS-PVA scaffold increased. PVA decreased the tensile strength and elongation of the membranes but increased the modulus. Swelling studies showed high swellability and complete degradation in the presence of phosphate-buffered saline. Cytocompatibility of the GEL-SS-PVA scaffolds showed that these had the highest potential to promote cell proliferation as evaluated with standard microscopy using L929 fibroblasts. The prepared GEL-SS composite scaffold incorporated with the PVA hydrogel was implanted in full-thickness articular cartilage defects in rats. The repair effect of cartilage defects was observed and evaluated among the GEL-SS-PVA, GEL-SS, and control operation groups. The defects were almost completely repaired after 14 weeks in the GEL-SS-PVA group, thereby indicating that the GEL-SS-PVA composite had a favorable effect on articular cartilage defects in rat knee joint repair.

tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are originated from the specific cleavage of endogenous tRNAs or their precursors and regulate gene expression when the cells are in stressful circumstances. Here, we replicated the rat common carotid artery (CCA) intimal hyperplasia model and investigated the expression of tRFs/tiRNAs in the artery. The normal and the balloon-injured rat CCAs were subjected to small RNA sequencing, and then the differentially expressed tRFs/tiRNAs were identified and analyzed. The expression profiles of tRFs/tiRNAs in the healthy and injured CCAs were remarkably different. tRNAGlnCTG-derived fragments (tRFGlnCTG) were found to be overexpressed with a high abundance in the injured CCA. In in vitro experiments, the synthetic tRFGlnCTG mimetics elevated the proliferation and migration of rat vascular smooth muscle cells (VSMCs). Through bioinformatics analysis and an overexpression experiment, tRFGlnCTG was found to negatively regulate the expression of FAS cell surface death receptor (FAS). This study revealed that tRFGlnCTG is a crucial regulator in promoting VSMC proliferation. The investigation of the roles of tRFs/tiRNAs is of significance for understanding the mechanism, diagnosis, and treatment of intimal hyperplasia., Graphical abstract, tRNA-derived fragments (tRFs) originated from the specific cleavage of tRNAs and regulate gene expression when the cells are in stressful circumstances. We described that tRFGlnCTG was highly expressed in the balloon-injured rat carotid artery. tRFGlnCTG was found to positively regulate VSMC proliferation via the FAS gene.

Objective Bernese periacetabular osteotomy (PAO), an effective treatment for patients with developmental dysplasia of the hip (DDH), is characterized by wide exposure, cancellous bone surgery, and difficult techniques. In addition, the hip joint is deep and of rich muscles and neurovascular supply, which significantly increases bleeding. For patients who had combined proximal femoral osteotomy (PFO), the blood loss may be tremendous. The blood management for PAO is still challenging. We aimed to evaluate the effectiveness of multi‐modal blood management for PAO and PAO combined with PFO. Patients and Methods We retrospectively evaluated patients who had PAO with or without combined procedures from June 2010 to December 2018 in our department. The multi‐modal blood management protocol included three parts: (i) pre‐operation – autologous component blood donation and iron supplement/erythropoietin; (ii) during operation – controlled hypotension anesthesia, intraoperative auto‐blood transfusion, tranexamic acid (20 mg/kg, IV / 0.5 g local), and standardized surgical procedure to shorten surgical time; and (iii) post‐operation – no drainage used, selective allo‐blood transfusion, and ice packing technique. As the lacking of the above standard blood management protocol during PAO or PAO + PFO initially, we divided all the patients into three groups: Group A (PAO) – before protocol started, 74 hips; Group B (PAO) – after protocol finalized, 178 hips; Group C (PAO + PFO) – after protocol finalized, 55 hips. The intraoperative blood loss, surgical time, allo‐transfusion rate, pre‐ and postoperative hemoglobin were compared among groups. Results Both the general characteristics and preoperative hemoglobin were comparable among the three groups (P, Perioperative multi‐modal blood management for periacetabular osteotomy with/without proximal femoral osteotomy can significantly decrease intraoperative blood loss, reduce allo‐transfusion rate from over 80% to 0%, and ensure the rapid recovery of postoperative hemoglobin level.

Objective To summarize the research progress of music therapy in hospice care and to provide reference for further research. Methods A wide range of literatures on music therapy and hospice care at home and abroad were searched and read, and the literature was integrated, judged, analyzed, and summarized. Results The related research on music therapy in hospice care mainly focused on western developed countries such as Europe and the United States. China is still in the stage of theoretical exploration, lacking qualitative research based on case investigation and empirical research based on data statistics. Conclusions Music therapy supports the management of symptoms in hospice care, which can meet the diverse needs of patients and their family members including physical, psychological, social, and spiritual.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 μM, 20-35 times stronger than that of acarbose (IC50, 180.0 μM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 μM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 μM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 μM and 142.3, 88.9, 39.2, and 40.8 μM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

Thermal oxidation stability is an important parameter for jet fuel practical application. In this work, in order to evaluate the influence of deoxygenation on fuel stability, samples of typical fuels (JP-10 and RP-3) were subjected to deoxygenation by nitrogen purge and then subjected to accelerated thermal oxidation (180°C, 200°C, and 220°C). The parameters of hydroperoxide number, total acid number, size distribution of insoluble oxidation products, and concentration of remaining antioxidant (butylated hydroxytoluene, MIT) were monitored and analyzed. The results show that deoxygenation and thermal oxidation have very little influence on the fuel physical properties (density, net heating value, and kinematic viscosity). However, deoxygenation significantly reduces hydroperoxide number, total acid number, and remaining BHT concentration in the fuel after accelerated oxidation. Moreover, the deoxygenation treatment also inhibits the formation of soluble macromolecular oxidatively reactive species (SMORS) and insoluble oxidation products such as gums and deposits.

Background : Acupuncture has been considered as a complementary or alternative therapy for children with tic disorders (TD), but its efficacy remains largely unknown. This study retrospectively examined the efficacy of acupuncture treatment for TD in children over the course of 12 weeks.Methods: Data were collected from Traditional Chinese Medicine clinics in a public pediatric hospital in Shanghai between June 2020 and March 2021. A total of 250 patients with TD were included in the study, with 122 patients exposed to acupuncture therapy combined with conventional treatment (observation group), and 128 patients exposed to conventional treatment alone (control group). Propensity score matching analyses were used to balance baseline characteristics, resulting in 78 matched patients for each group. Reductions in the Yale Global Tic Severity Scale (YGTSS) total score were analyzed in the two groups after 12 weeks of treatment.Results: The two groups reached equilibrium in terms of baseline demographic characteristics and YGTSS total score after the propensity score matching (P > 0.05). Compared to the control group, the reduction in the YGTSS total score after 12 weeks of treatment was greater for the observation group (OR = 2.94, 95% CI: 1.03, 8.39, P = 0.04), and this association was stronger for patients who had significant vocal tics (β = 0.29, 95% CI: 0.88, 2.68, P = 0.001). The clinical efficacy for the observation group was significantly better than the control group.Conclusions: We provided preliminary evidence supporting the therapeutic effect of acupuncture for TD in children. Hence, our findings indicate that acupuncture could be an adjuvant treatment efficacious for TD in children, especially for vocal tics.

Background Platelet-rich plasma (PRP) has been frequently used to enhance bone regeneration. A meta-analysis was conducted to systematically assess the fusion rate and pain relief of applying PRP during spinal fusion surgery. Methods Studies investigating spinal fusion surgery combined with PRP were retrieved from Medline and the Web of Science in accordance with the inclusion and exclusion criteria. A quality evaluation was conducted using the Cochrane collaboration tool for randomized controlled trials and the Newcastle-Ottawa scale quality assessment for cohort trials. Statistical analysis was performed using RevMan, version 5.3. Results A total of 12 studies, including 3 randomized controlled trials and 9 cohort studies, with 661 patients, were included in the present meta-analysis. The mean age was 52.3 ± 8.0 years. Overall, the pooled results demonstrated that the differences in the fusion rates between the PRP and non-PRP treatment groups were not statistically significant. The risk ratio was 1.01 (95% confidence interval, 0.95–1.06; P = 0.83). Also, no significant difference in pain relief measured using the visual analog scale was found between the 2 groups. The mean difference was −0.08 (95% confidence interval, −0.26 to 0.11; P = 0.42). conclusions Adding PRP did not increase the fusion rates from spinal fusion surgery. In addition, no significant difference was found in pain relief between the PRP and non-PRP treatment groups.

Spiroseoflosterol (1), a 7(8→9)-abeo-ergostane steroid with a unique spiro[4.5]decan-6-one system, was isolated from the fruiting bodies of Butyriboletus roseoflavus. Its structure was determined by interpretation of comprehensive spectroscopic, X-ray, and computational data. A plausible biogenetic pathway for spiroseoflosterol (1) was postulated based on a key semipinacol rearrangement. Compound 1 was cytotoxic to HepG2 and Huh7/S (sorafenib-resistant Huh7) with IC50 values of 9.1 and 6.2 μM, respectively.

Previous investigations showed inconsistent results for associations between vitamin D and knee osteoarthritis (OA). The present study aimed to make a systematic review and meta-analysis for the association between vitamin D and knee OA.We systematically searched for articles published in the databases PubMed, Web of Science, EMBASE, Medline, and Google Scholar through July 2019. All statistical analyses were made using STATA 12.0 software. The Q test and IThe study indicated that there were no significant associations between serum levels of 25-hydroxy (OH) vitamin D and prevalence, incidence or progression of knee radiographic OA (ROA), and joint space narrowing (JSN). However, a subgroup study showed significant associations of low vitamin D levels with the progression of knee OA. Additionally, the present study showed no significant effect of vitamin D supplementation on knee OA.The results do not support that serum levels of 25(OH) vitamin D are associated with the risks of knee OA, except perhaps with progression of knee OA. In addition, vitamin D supplementation may not have a clinically significant effect on pain control or structure (tibial cartilage volume and JSW) progression in patients with knee OA. Longer-term clinical trials are essential to explore the effect of vitamin D supplementation on knee OA.Frühere Untersuchungen ergaben inkonsistente Ergebnisse für Assoziationen zwischen Vitamin D und Knie-Osteoarthritis (Knie-OA). Die vorliegende Studie zielte auf eine systematische Überprüfung und Metaanalyse des Zusammenhangs zwischen Vitamin D und Knie-OA ab.Wir haben systematisch nach Artikeln gesucht, die in folgenden Datenbanken (PubMed, Web of Science, EMBASE, Medline und Google Scholar) bis Juli 2019 veröffentlicht wurden. Alle statistischen Analysen wurden mit der Software STATA 12.0 durchgeführt. Der Q-Test und IDie Studie ergab, dass keine signifikanten Zusammenhänge zwischen dem Serumspiegel von 25-Hydroxy-Vitamin D (25-OH-Vitamin D) und der Prävalenz, Inzidenz oder Progression von radiografischem OA (ROA) und Gelenkspaltverengung (JSN) im Knie bestehen. Eine Subgruppenstudie zeigte jedoch signifikante Assoziationen niedriger Vitamin-D-Spiegel mit dem Fortschreiten der Knie-OA. Zusätzlich zeigte die vorliegende Studie keinen signifikanten Effekt der Vitamin-D-Supplementierung auf die Knie-OA.Die Ergebnisse belegen nicht, dass Serumspiegel von 25-OH-Vitamin D mit dem Risiko einer Knie-OA assoziiert waren, außer vielleicht mit dem Fortschreiten der Knie-OA. Darüber hinaus hat eine Vitamin-D-Supplementierung möglicherweise keinen klinisch signifikanten Einfluss auf die Schmerzkontrolle oder den Strukturverlauf (Tibiaknorpelvolumen und JSW) bei Patienten mit Knie-OA. Langfristige klinische Studien sind unerlässlich, um die Wirkung der Vitamin-D-Supplementierung auf die Knie-OA zu untersuchen.

Background Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years. The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results Using fold change≥2.0 or ≤ 0.5 and p ≤ 0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR = 3.149, 95%CI:1.018–9.115, p = 0.034), whereas combining the former two is independent for OS (HR = 5.146, 95%CI:1.674–15.817, p = 0.04). Conclusions For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.

Abstract Uncariae Ramulus Cum Uncis (Gou-Teng), the dried hook-bearing stems of several Uncaria plants (Rubiaceae), is a well-known herbal medicine in China. The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between different species. In order to discern their chemical and biological difference, an ultra-fast liquid chromatography equipped with ion trap time-of-flight mass spectrometry (UFLC-IT/TOF-MS) combining with melatonin (MT1 and MT2) and 5-hydroxytryptamine (5-HT1A and 5-HT2C) receptors agonistic assay in vitro was conducted on seven Uncaria species. As a result, 57 compounds including 35 indole alkaloids, ten flavonoids, five triterpenoids, five chlorogenic analogues, and two other compounds were characterized based on their MS/MS patterns and UV absorptions. Specifically, cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens, whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants. Three Uncaria species, U. rhynchophylla, U. macrophylla, and U. yunnanensis showed obviously agnostic activity on four neurotransmitter receptors (MT1, MT2, 5-HT1A, and 5-HT2C). This first-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientific viewpoints for the clinical application of Gou-Teng. Graphic Abstract

Ferric oxides and (oxy)hydroxides, although plentiful and low-cost, are rarely considered for oxygen evolution reaction (OER) owing to the too high spin state (eg filling ca. 2.0) suppressing the bonding strength with reaction intermediates. Now, a facile adsorption-oxidation strategy is used to anchor FeIII atomically on an ultrathin TiO2 nanobelt to synergistically lower the spin state (eg filling ca. 1.08) to enhance the adsorption with oxygen-containing intermediates and improve the electro-conductibility for lower ohmic loss. The electronic structure of the catalyst is predicted by DFT calculation and perfectly confirmed by experimental results. The catalyst exhibits superior performance for OER with overpotential 270 mV @10 mA cm-2 and 376 mV @100 mA cm-2 in alkaline solution, which is much better than IrO2 /C and RuO2 /C and is the best iron-based OER catalyst free of active metals such as Ni, Co, or precious metals.

BACKGROUND Congenital short bowel syndrome (SBS) associated with malrotation, gut volvulus and jejuno-ileal atresia is a very rare condition. It is a severe challenge for surgeons to preserve residual ischemic bowel segment in the management of short bowel syndrome,especially in neonates. CASE SUMMARY We report a newborn baby with gut malrotation associated with jejuno-ileal atresia, congenital SBS and jejunal volvulus. Hematemesis and abdominal distention were noted. At laparotomy, malrotation associated with jejuno-ileal atresia, congenital SBS and jenunal volvulus was confirmed. The total length of the small bowel was 63 cm with proximal jejunal bowel segment measuring 38 cm, including 18 cm necrotic segment below the Treitz’s ligament and 20 cm severe ischemic segment. The distal part of the small bowel was 25 cm in length and only about 0.8 cm in diameter. Ladd’s procedure, necrotic segment resection and end-to-back duodeno-ileal anastomosis were performed. The residual severe ischemic jejunum was preserved with single proximal stoma and distal end closure. Three months later, to restore the continuity of the isolated gut segment, end-to-end duodeno-jejunal and jejuno-ileal anastomosis was performed. The entire functional small bowel length increased to 80 cm. Intravenous fluid therapy and parenteral nutrition were discontinued on the 10th day postoperatively. Twelve months later, her body weight was 9.5 kg. CONCLUSION Isolation of severe ischemic bowel segment and staged anastomosis to restore the gut continuity for infants with SBS are safe and feasible.

In this work, we report a series of poly(itaconic acid‐co‐acrylic acid‐co‐acrylamide) (poly(IA‐co‐AAc‐co‐AAm)) hydrogels via frontal polymerization (FP). FP starts on the top of the reaction mixture with aid of heating provided from soldering iron gun. Once polymerization initiated, no further energy is required to complete the process. The influences of IA/AAc weight ratios on frontal velocities, temperatures, and conversions on the reaction time are thoroughly investigated and discussed where the amount of AAm monomer remains constant. Fourier transform‐infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscope (SEM), dynamic mechanical analysis, and the swelling measurement are applied to characterize the as‐synthesized poly(IA‐co‐AAc‐co‐AAm) hydrogels. Interestingly, the swelling ratios of the hydrogels are changed with different IA/AAc contents, and the maximum swelling ratios are ~4439% in water. SEM images describe highly porous morphologies and explain good swelling capabilities. Moreover, the poly(IA‐co‐AAc‐co‐AAm) hydrogels exhibit superior pH‐responsive ability. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2214–2221

Terminthia paniculata (Sanyeqi) is widely used for treating inflammation and rheumatic arthritis in the folk areas of Yunnan province, China. Its total extract was first revealed with xanthine oxidase (XO) inhibitory activity in vitro and anti-hyperuricemic effect in vivo. Bioassay-guided separation on Fr. A5 yielded six chalcone-flavonone heterodimers, termipaniculatones A-F. Their structures were elucidated based on extensive spectroscopic analyses involving HRESIMS, 1D and 2D NMR, UV, IR and [α]D, and the absolute configuration of termipaniculatone F was verified by ECD calculation. Termipaniculatones A and E showed obvious XO inhibitory activity with IC50 values of 55.6 and 89.5 μM, respectively, which took effects via a mix-type mode. A molecular modeling study revealed that termipaniculatone A was well located into the active site of XO by interacting with Glu802, Arg880, Thr1010 and Val1011 residues. Termipaniculatone A showed anti-hyperuricemic effects by decreasing serum uric acid levels and inhibiting XO activity in both serum and liver on potassium oxonate (PO)-induced hyperuricemia mice, and anti-inflammatory activity through alleviating paw swelling on monosodium urate (MSU)-induced mice, at the concentration of 20 mg/kg. This is the first time to reveal the anti-hyperuricemic and anti-acute gouty arthritis potency of T. paniculata and the characteristic biflavonoids as active constituents, which provides valuable information for searching new XO inhibitors from natural sources.

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls ( 1 − 9 ), including six new ones ( 2 − 5 , 7 and 9 ), were isolated from the EtOAc extract of G. elata . Five compounds 1 , 3 , 4 , 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT 1 and MT 2 receptors with EC 50 values of 237 and 244 μM. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para -hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT 2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.

Introduction and objectives Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. Methods Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography–tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. Results Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P Conclusion Chronic HBV infection may impact on the serum lipidomics and steatosis-related pathological characteristics of NAFLD.

Background Vertebral augmentation (VA) techniques are used to treat acute osteoporotic vertebral compression fractures (OVCFs). However, the incidence of recurrent vertebral fractures after VA is controversial. Various factors have been discussed in the literature, but no convincing study on the quality of paraspinal muscles has been reported. The purposes of this study were to evaluate the changes in paraspinal muscles and discuss the relationship between paraspinal muscle degeneration and vertebral refractures after percutaneous kyphoplasty (PKP). Methods This retrospective study was conducted in patients who underwent PKP for an initial OVCF between July 2017 and August 2018. Patients were followed up and categorized in the refractured or non-refractured group. A final magnetic resonance imaging (MRI) scan and a preoperative MRI scan were used to determine the measurements. The paraspinal muscles at the mid-height level of the initial fractured vertebral body were measured using regions of interest (ROIs), including the cross-sectional area (CSA) and signal intensity (SI). The changes in the observed data were compared between the groups using rank-sum tests. Results Overall, 92 patients were enrolled in the study; 33 of them sustained vertebral refractures during the follow-up and the other 59 patients did not. There were no significant differences in terms of sex, age, preoperative bone mineral density, and body mass index between the groups (all, P > 0.05). The refractured group had a significantly higher decrease in the ROI-CSA and CSA/SI, and a higher increase in ROI-SI, compared with the preoperative data (all, P < 0.05). Conclusions The quality of paraspinal muscles significantly decreased in patients with new OVCFs after PKP. This brings a new perspective to the study of postoperative recurrent fractures; patients and physicians need to pay more attention to the efficacy of bed rest and bracing.

This study assessed the efficacy and safety of tirofiban in combination with dual-antiplatelet therapy (DAPT) in progressive ischemic stroke. One hundred and four patients equally divided into a tirofiban group or DAPT group were enrolled from June 2018 to December 2019. Efficacy outcomes included National Institutes of Health Stroke Scale score for 14 days, and modified Rankin scale (mRs) scores as excellent (mRs 0-1) or favorable (mRs 0-2) measured 90 days after stroke. At 14 days, the tirofiban group had a lower National Institutes of Health Stroke Scale score compared with the DAPT group (F = 14.959, P = 0.000). The mRS scores of the 2 groups at 90 days after treatment were significantly different from those before treatment. At 90 days, excellent favorable functional outcome (mRS ≤ 2) was achieved in 33 of 52 (63.43%) patients in the tirofiban group compared with 25 of 52 (48.08%) patients in the DAPT group. The incidence of bleeding was 5.77% in the tirofiban group, compared with 0% in DAPT group. Intravenous (IV) tirofiban alone or combined with DAPT was shown to be safe and effectively improved clinical outcome in progressive ischemic stroke patients. IV tirofiban was shown to be superior to the DAPT regimen.

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, three new polybenzyls, gastropolybenzylols G-I (1–3) were isolated from the EtOAc extract of G. elata. Their structures were identified by extensive spectroscopic analyses involving HRESIMS, UV, IR, 1D and 2D NMR. Compound 1 showed agonistic effects on MT1 and MT2 receptors with agonistic rates of 55.91±4.84% and 165.13±5.65% at the concentration of 0.5 mM, respectively, and an EC50 value of 76.24 μM on MT2 receptor. Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s13659-019-0213-2) contains supplementary material, which is available to authorized users.

Purpose The objective of this study was to characterize the population pharmacokinetics of voriconazole and to identify factors that significantly affect pharmacokinetic parameters and to further investigate optimal dosage regimens in Chinese adult patients with hematologic malignancies. Methods A prospective population pharmacokinetic analysis was performed on 186 concentration measurements obtained from 41 adult patients with hematologic malignancies. All enrolled patients were treated with voriconazole for diagnosed or suspected invasive fungal diseases. Oral voriconazole was routinely administered at a maintenance dose of 200 mg q12h. Serial blood samples were collected after steady-state of each patient. Monte Carlo simulation was applied to optimize dosage strategies. Findings A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.18 L/h, the volume of distribution was 88.9 L, and the absorption rate constant was 0.729 h−1. Clearance and steady-state exposure (AUC0–12) were found to be significantly associated with age and CYP2C19 phenotype. The average AUC0–12 of elderly patients (aged 60–90 years) was 2.1 times higher than that of relative younger patients (aged 18–59 years). The average AUC0–12 of poor metabolizers (PMs) was approximately 2.5 and 1.8 times higher than that of extensive and intermediate metabolizers (IMs), respectively. Considering both efficacy and tolerability, dosage regimens of 100 and 50 mg orally administered every 12 hours were recommended for elderly IMs and PMs, respectively. Implications A population pharmacokinetic model for voriconazole in Chinese adult patients with hematologic malignancies was successfully developed and could well capture voriconazole's pharmacokinetic characteristics. Age and CYP2C19 phenotype were found to significantly influence voriconazole clearance and should be taken into consideration clinically for dose optimization. The optimal dosage strategies in specific clinical scenarios were proposed in this study based on model simulation. Because of the high incidence of mutant CYP2C19*2 and *3 alleles, genetic testing seems to be necessary for Asian elderly patients when voriconazole treatment is initiated.

Ethnopharmacological relevance Traditional Chinese medicines (TCMs) are fascinating sources for natural drug candidates. Uncaria rhynchophylla (Gouteng) is a famous TCM used for alleviating central nervous system (CNS) disorders, while its antidepressant constituents are still disputed. Aim of the study The present study was designed to assess the antidepressant property of U. rhynchophylla and characterize the active constituents targeting melatonin receptors which are closely related to CNS diseases. Materials and methods The total extract and each fraction of U. rhynchophylla were extensively assessed for their agonistic activity on melatonin receptors in vitro. The following bioassay-guided fractionation yielded the active constituents, whose activity was confirmed by dose-dependent bioassay and antagonistic experiment on HEK293 cells. Their antidepressant effects were evaluated on forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) mice models in vivo. Their metabolic profiles in mice plasma were analyzed by LCMS-IT-TOF. Results The stems and hooks of U. rhynchophylla were revealed with agonistic activity on melatonin receptors (MT1 and MT2). Under the guidance of bioassay, two flavanols, catechin and epicatechin were obtained and showed obviously activity agitating MT1 (EC50 = 25.8 and 156.1 μM) and MT2 (EC50 = 47.3 and 208.8 μM) receptors. The agonistic activity of catechin on melatonin receptors can be antagonized by luzindole at the concentrations of 1.57–100 μM. Catechin could significantly reduce the immobility time in both FST and TST mice models at doses of 80 and 40 mg/kg, without obvious effect on locomotor activity in OFT mice model. Five phase II (M1-M5) and one phase I (M6) metabolites of catechin were detected in mice plasma after intragastric (i.g.) administration. Conclusion Catechin is a potent antidepressant candidate from U. rhynchophylla by targeting melatonin receptors. The main metabolic pathways of catechin in mice plasma are glucuronidation (M3) and methylated glucuronidation (M4 and M5). This study provides valuable information for understanding the antidepressant potency of Gouteng and its active constituents.

Background: Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear. Methods: We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We divided each treatment groups into sub-groups based on the median expression levels of ACTN1-4. Results: Survival analysis showed that in the chemotherapy-only group, high ACTN1 and ACTN3 expression were associated with shorter event-free survival (EFS) and overall survival (OS) (p

Objective: To investigate the effects of exogenous α-linolenic acid (ALA) on in vitro maturation (IVM) and developmental competence of human oocytes. Methods: Experiment 1 examined the effects of ALA at different concentrations (0 [control], 10, 50, 100, and 200 μmol/L) in the IVM medium on oocyte maturation. Treatment with 50 μmol/L ALA significantly accelerated oocyte maturation (P < 0.05) and resulted in significantly higher mitochondrial DNA (mtDNA) copy number compared to the control. Hence, 50 μmol/L ALA was selected for combination with follicular fluid (FF) to investigate oocyte developmental potential. mtDNA of the matured oocyte was analyzed by real-time polymerase chain reaction. Experiment 2 investigated the effects of FF with optimal ALA concentration (Group A: ALA + FF + IVM medium) or without ALA (Group B: FF + IVM medium) on oocyte maturation, fertilization, 2 pronuclear cleavage, and embryo and blastocyst development. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured for maturation medium from Group A, Group B, and Group C (control group, IVM medium only). Results: Treatment with 50 μmol/L ALA obviously accelerated oocyte maturation (P < 0.05) and resulted in significantly higher mtDNA copy number (P < 0.05) in the matured oocytes compared to the control (0 μmol/L ALA). Supplementation of 50 μmol/L ALA and FF (Group A) obviously increased the total maturation rate than FF-treated group (Group B) which has higher (P < 0.05) total maturation rate than that of Group C. However, no significant differences were observed in fertilization, embryo availability, and blastocyst production among Group A, B, and C. Treatment with 50 μmol/L ALA decreased the level of MDA (P < 0.05), but had no effect on the activity of SOD in the IVM medium. Conclusions: Our results suggested that the treatment with 50 μmol/L ALA during IVM improves maturation in human oocytes. It is also likely to improve embryo availability and blastocyst formation. This might be associated with the alteration of mtDNA replication (increased mtDNA copy number) and the reduction of oxidative stress (reduced MDA level).

Despite the advancement of medical science, diseases are part-and-parcel of human life. Plants have provided humans with medicines since time immemorial, and are still one of the primary sources for drug discovery. Brassica rapa L., commonly known as turnip, is one of the world's oldest cultivated vegetables. Besides being an important vegetable and source of oil, turnip is also used as a traditional medicine for the treatment of headaches, chest complaints, rheumatisms, oedemas, gonorrhoea, syphilis, and rabies. Glucosinolates and isothiocyanates (mainly 2-phenylethyl, 4-pentenyl, and 3-butenyl derivatives) are the main constituents of turnip with diverse bioactivities, especially for the protective effect against cancers. Besides, flavonoids, phenolics, indoles and volatiles are also concomitant in this plant. Pharmacological investigation on turnip revealed the antitumor, antihypertensive, antidiabetic, antioxidant, antiinflammatory, hepatoprotective, and nephroprotective effects. The anticancer property was found to be the most promising biological activity of turnip with 2-phenylethyl isothiocyanate, phenylpropionitrile, brassicaphenanthrene A, 6-paradol, and trans-6-shogaol as the major active constituents. Flavonoids and phenolics with high free radical scavenging activity should be corresponding to the antioxidant effects. Arvelexin, an indole derivative in turnip, was reported with various effects involving antiinflamatory, antihypertensive and hypolipidemic potency. In spite of many studies concerning either the chemical constituents or the biological activities of turnip, only a few cases disclosed the active ingredients responsible for diverse bioactivities. This review summarizes the research progress on the chemistry and health-benefits of turnip over the past 20 years to provide a reference for the further investigation.

Ethnopharmacological relevance Artemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated. Aim of the study This study is to reveal the active part of A. capillaris, and systemically investigate the enynes and their anti-HBV activity. Materials and methods The total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro. Results ACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris. Twelve enynes (1–12) involving four new ones (1–4) and two unusual enyne analogs (13–14) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM. Conclusions Enynes are responsible for the anti-HBV effects of A. capillaris. Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris, which provides valuable information for understanding the ethnopharmacological application of Yin-Chen.

AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease (NAFLD). METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms (SNPs) in PNPLA3. Ultra performance liquid chromatographytandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs (rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine (LPC), lysophosphatidylcholine plasmalogen (LPCO), lysophosphatdylethanolamine (LPE), phosphatidylcholine (PC), choline plasmalogen (PCO), phosphatidylethanolamine (PE), ethanolamine plasmalogen (PEO)], of NAFLD patients. PNPLA3 rs139051 (A/A genotype) and rs2294918 (G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs (LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs (LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD (rho: -0.407 to -0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50 (0.00, 1.75) vs 1.50 (1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile. CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an up-regulatory effect on serum phospholipids of LPCs and LPCOs, which are associated with low-grade lobular inflammation of NAFLD.

Background Renal toxicity limits the clinical use of platinum-based therapy in the elderly. In order to clarify the impact of aging on the risk of platinum-related nephrotoxicity, the following meta-analysis was performed. Methods We searched multiple databases for studies published before January 2017. The inclusion criteria were case-control, cohort studies published in any language. Results The risk of platinum-induced nephrotoxicity in the older group was 1.43 times (risk rate) higher than in the non-older group. Platinum-induced nephrotoxicity in older patients was mainly I/II. There was no significant difference in the incidence of grade III/IV renal toxicity between groups. The risk for elderly patients in Asia was significantly higher than in Europe and North America. Carboplatin had a lower risk of renal toxicity and only half of the amount of moderate and severe nephrotoxicity than cisplatin. In the age stratification analysis, the RR values were 1.43, 1.51 and 1.35 respectively for the elderly group (55, 60, 70 years old), and all had significant differences. The risk of platinum-related nephrotoxicity in elderly patients was significantly increased in the high comorbidity rate group. Moreover, the RR values of the normal renal function group were significantly higher than that of the ‘no mention or renal insufficiency’ subgroup. Conclusions Aging increased the risk of platinum-induced nephrotoxicity by 43%, partly due to more comorbidities in elderly patients, and mild renal toxicity was dominant. The risk of renal toxicity of the elderly patients in Asian countries was much higher than that of in European countries and North America.

Pollination dynamics was studied in a first-generation Platycladus orientalis (L.) Franco seed orchard with pedigree reconstruction using eight nuclear and four chloroplast SSRs. The pedigree reconstruction assigned 371 of 448 studied seeds to one of the orchard’s 192 candidate male parents and showed a high level of outcrossing and pollen contamination in the orchard’s seed crop. While the orchard’s seed population showed greater allelic richness compared with the parental population, a few alleles present in the parental population were missing in the seed crop. Additionally, we detected no significant correlation between male reproductive energy (pollen yield) and male reproductive success; however, uneven parental contribution was also observed. Pollen management practices were recommended to ensure the maintenance of genetic diversity in the seed crops and increase in genetic gain.

Application of AO spine injury classification system (AOSICS) to identify the timing of operation for different types of traumatic thoracic/thoracolumbar incomplete spinal cord injury (SCI).A single-center prospective cohort study was conducted to enroll patients with thoracic/thoracolumbar incomplete SCI from April 2013 to November 2016; they were divided into an early group (24 hours after SCI) and a late group (24-72 hours after SCI). Each group was divided into A, B, C subgroups according to AOSICS. The primary outcomes were ordinal changes in ASIA Impairment Scale at 12-month follow-up. The secondary outcomes included the Medical outcomes study 36-term short form health survey physical component summary (PCS), complications, mortality, and hospital length of stay (LOS).Seven hundred twenty-one patients with thoracic/thoracolumbar incomplete SCI were included; 335 patients underwent early surgery, and 386 patients underwent delayed surgery. Statistical results included the following comparisons of the early versus late groups: AIS improvement of 1 grade or more (combined groups: P = 0.009, odds ratio [OR] = 1.487; A: P = 0.777, OR = 1.072; B: P = 0.029, OR = 1.701; C: P = 0.007, OR = 1.762), AIS improvement 2 grades or more (combined groups: P = 0.002, OR = 2.471; A: P = 0.189, OR = 3.939; B: P = 0.011, OR = 2.550; C: P = 0.035, OR = 3.964) and PCS (combined groups: P = 0.327; A: P = 0.776; B: P = 0.019; C: P = 0.562). LOS (combined groups: P0.0001; A, B and C: P0.0001). Complications (combined groups: P = 0.267; A: P = 0.830; B: P = 0.111; C: P = 0.757).Patients with type-A injuries with incomplete SCI do not have to undergo aggressive early operations. Patients with type-B and type-C injuries should undergo an operation early to achieve better clinical results.

The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.

Qing Li,1 Juan Mu,1 Jijun Yuan,2 Zhenxing Yang,2 Jia Wang,1 Qi Deng1 1Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, People’s Republic of China; 2Medical Department, Shanghai Genbase Biotechnology Co., Ltd, Shanghai 201203, People’s Republic of ChinaCorrespondence: Qi Deng Email kachydeng@126.comPurpose: To investigate the donor chimerism changes and curative effects associated with the use of autologous anti-CD19 chimeric antigen receptor (CAR) T cells with B-cell acute lymphoblastic leukemia (B-ALL) presenting with a low donor chimerism level and relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT).Methods: Nine patients with B-ALL showing low donor chimerism level and relapse after allo-HSCT were enrolled. Patients 1– 3 received CD19 CAR-T cell therapy using cells derived from autologous peripheral blood mononuclear cells (PBMCs) (comprising a mixture of patient and original donor cells) as their donors could not provide PBMCs. Samples from the other six patients (Patients A–F) were investigated only in vitro. The changes in the degree of donor chimerism, function of the CD19 CAR-T cells and T cells in all nine patients were analyzed in vitro. The therapeutic effects and adverse events (AEs) were also evaluated in Patients 1– 3.Results: The CAR-T cells and T cells in all nine patients showed complete donor chimerism restoration following a 12-day culture period in vitro. These CD19 CAR-T cells demonstrated strong cytotoxicity towards Nalm 6 cells in vitro except in patients 3 and D. In the latter patients, the absolute numbers of all subsets, especially the CD8 + T-cell absolute numbers in peripheral blood were very low. Patients 3 and D showed relatively short durations from transplant to recurrence and received chemotherapy after relapse. In the patients receiving CD19 CAR-T cell therapy, the most commonly observed AE was grade 1 to 2 cytokine release syndrome. None of the cases showed acute graft-versus-host disease during treatment. Patients 1 and 2 achieved complete response with complete restoration of donor chimerism. Patient 3, who received the same CD19 CAR-T cell therapy, did not respond to this therapy.Conclusion: CD19 CAR-T cells derived from patients relapsed after allo-HSCT with a low level of donor chimerism were effective for salvage therapy and could restore to complete donor chimerism after 12 days’ culture in vitro.Trial Registration: Humanized CD19 CAR-T cell therapy for relapse or refractory B-cell lymphoma or acute B lymphocytic leukemia, ChiCTR1800019622, Registered 24 November 2018, http://www.chictr.org.cn/index.aspx.Keywords: chimeric antigen receptor, acute lymphoblastic leukemia, allogeneic hematopoietic stem cell transplant, relapse, donor chimerism

Background: To improve the prognosis of burn patients with renal replacement therapy (RRT), we performed this systematic review and meta-analysis.Methods: We searched multiple databases for studies published before February 2020. Studies about adult populations with burn injury, providing epidemiologic data on prevalence or mortality of RRT, were included. Results: A total of selected 58 studies, including 38,787 patients were enrolled in our analysis. The prevalence rates of RRT were 5.14% (95%CI 4.54%-5.74%) in all burn patients and 35.8% (95%CI 29.54%-42.07%) in acute kidney injury (AKI) patients. The prevalence of RRT among burn patients in the intensive care unit (ICU) was 10.92% (95%CI 8.71%-13.14%). The mortality of all burn patients with RRT was 65.52% (95%CI 58.41%-72.64%). The mortality of patients with RRT in ICU was 62.7% (95%CI 53.7%-71.7%). The mortality rate of RRT patients was 30.33% (95%CI 22.06%-38.59%) of the total. There was no significant correlation (r=-0.224, P=0.159) between the year of publication and the mortality of burn patients with RRT. Neither cohort studies nor RCT studies of subgroup analyses show that RRT could reduce the risk of death in burn patients with AKI. Bleeding (10.92%) and secondary infection (9.61%) were the most common RRT-related adverse reactions. Compared with heparin, regional citrate anticoagulation has advantages in superior filter life spans and fewer bleeding episodes. Dialysis-requiring AKI in burn patients could increases the risk of chronic kidney disease progression and end-stage renal disease. About 35% of RRT patients need to maintain hemodialysis temporarily, even if they survive and leave hospital. Conclusions: The prevalence of RRT is not low; approximately, one-third of burn patients with AKI need RRT. The mortality of burn patients with RRT is very high and accounts for 1/3 of the total deaths. There is no evidence that RRT can improve the prognosis of burn patients with AKI. Regional citrate anticoagulation has some advantages in reducing bleeding and extending filter life spans, which may be more suitable for severe burn patients with CRRT.

Meckel’s diverticulum (MD) is a relatively common true congenital diverticulum on the ileum. Bleeding caused by polypoid hyperplasia of ectopic gastric mucosa in MD is rare. A 14-year-old Chinese boy presented with intermittent melena and haematochezia for 1 month. Laboratory data showed normocytic anaemia. Gastroscopic findings were normal. The patient underwent exploratory laparotomy without bowel preparation on day 2 because of sudden haematochezia and decreased haemoglobin. Intraoperative colonoscopy revealed inflammatory changes in the terminal ileal mucosa with diffuse haemorrhage. Melena with decreased haemoglobin recurred 20 days after the first operation. Computed tomography (CT) and angiography revealed a tubular lesion that was localised in the right lower abdominal quadrant. Single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging with 99m-technetium pertechnetate confirmed moderately increased uptake in the distal ileum. Retrograde double-balloon enteroscopy (DBE) showed a diverticulum with prominent mucosal polypoid hyperplasia at an insertion depth of 100 cm from the anastomotic stoma. Diverticulectomy and end-to-end anastomosis were performed, and MD was confirmed by a histopathological examination. The patient’s postoperative recovery was uneventful during the 2-month follow-up. MD with polypoid hyperplasia of ectopic gastric mucosa is rare. Complementary use of DBE and SPECT/CT can accurately diagnose MD by providing anatomical and functional information.

Objective This study was performed to test whether ATG16L1 rs2241880, rs6758317 and ATG16L2 rs11235604 polymorphisms were associated with RA and further examine the genetic interaction between ATG16L1 and ATG16L2 in RA among a Chinese population. Methods A total of 594 RA patients and 604 healthy controls were included, and the genetic polymorphisms were genotyped based on HI-SNP technology. Results Significant associations of ATG16L1 rs2241880 polymorphism with RA (T/T versus C/T + C/C, OR = 1.32, 95% CI 1.04–1.67, P = 0.02), cyclic citrullinated peptide (CCP)-positive RA (genotype comparison, P = 5.38 × 10−3; T/T versus C/T + C/C, OR = 1.45, 95% CI 1.12–1.87, P = 4.86 × 10−3) and rheumatoid factor (RF)-positive RA (genotype comparison, P = 0.03; T versus C, OR = 1.23, 95% CI 1.01–1.49, P = 0.04; T/T versus C/T + C/C, OR = 1.44, 95% CI 1.10–1.88, P = 7.62 × 10−3) were found. Significant genetic interaction between ATG16L1 rs2241880 and ATG16L2 rs11235604 was associated RA (P = 0.03), and significant genetic interaction between ATG16L1 rs6758317 and ATG16L2 rs11235604 was associated with RA (P = 7.57 × 10−3), CCP-positive RA (P = 0.01) and RF-positive RA (P = 0.01). Consistently, stratification analysis found that significant associations of RA with ATG16L1 rs2241880, rs6758317 polymorphisms were only detected among individuals carrying C/T genotype of the ATG16L2 rs11235604 polymorphism. Conclusions Our results indicated that ATG16L1 rs2241880 polymorphism was associated with RA in Chinese population, and provided evidence for genetic interaction between ATG16L1 and ATG16L2 in determing the development of RA, highlighting the involvement of autophagy in the pathogenesis of RA.

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.