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Zheng Yuan, Xinhua GuDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of ChinaAbstract: A novel rhein formulation based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) suitable for oral administration was developed in this study. The designed nanosystems were obtained by a modified spontaneous emulsification solvent diffusion method. The morphology of rhein-loaded PLGA NPs showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the NPs was 140.5±4.3 nm, and the zeta potential was -16.9±3.1 mV. The average drug loading was 3.9%±0.7%, and encapsulation efficiency was 84.5%±6.2%. Meanwhile, NPs are characterized by the slower release (only about 70% of rhein is released within 5 hours), and the model that fitted best for rhein released from the NPs was Higuchi kinetic model with correlation coefficient r=0.9993, revealing that rhein could be controlled released from the NPs. In vivo, NPs altered the distribution of rhein, and the half-life after oral administration was prolonged remarkably more than those of suspensions (22.6 hours vs 4.3 hours). The pharmacokinetic results indicated that the NPs had sustained-release efficacy. The area under the curve0–∞ of the NPs formulation was 3.07-fold higher than that of suspensions, suggesting that the encapsulated rhein had almost been absorbed in rats over the period of 12 hours. Although rhein-loaded PLGA NP formulations are hopefully used as a chemotherapeutic or adjuvant agent for human gastric cancer (SGC-7901), their in vivo antitumor effect and mechanisms at the molecular level still need further study.Keywords: rhein, PLGA, nanoparticles, release, pharmacokinetics, SGC-7901

The Indo-Chinese green peafowl Pavo muticus imperator (Galliformes: Phasianidae) is an endangered bird species. However, our present knowledge of the species composition of nematode parasites of this bird remains limited. In the present study, two nematode parasites Heterakis pedioecetes Mawson, 1956 (Ascaridomorpha: Heterakoidea) and Synhimantus (Dispharynx) nasuta (Rudolphi, 1819) (Spiruromorpha: Acuarioidea) were reported from P. muticus imperator for the first time. The detailed morphology of these two nematode species was further studied using light and scanning electron microscopy, and some previously unreported morphological features were revealed. These supplementary morphological and morphometric data contributed to a more accurate identification of these two common avian nematodes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis., Methods: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats., Results: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05)., Conclusion: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Abbreviata baltazardi Chabaud, 1953 (Nematoda: Physalopteridae) is a hitherto poorly known parasitic nematode species reported from Phrynocephalus helioscopus Pallas (Squamata: Agamidae) in Iran. The current knowledge on the morphology of A. baltazardi is still very limited. In the present study, the detailed morphology of A. baltazardi was studied using light microscopy and, for the first time, scanning electron microscopy, based on newly collected specimens from the yarkand toad-headed agama P. axillaris Blanford Pallas (Squamata: Agamidae) in China. Some erroneous or previously unreported morphological features of A. baltazardi were observed using SEM, which include the presence of one large semicircular protrusion and 20-30 denticles on each pseudolabium, the absence of precloacal medioventral papilla in some individuals and the presence of 4-5 postcloacal medioventral papillae in males. SEM observations also clearly showed the detailed morphology of deirids, cloacal ornamentation, caudal papillae, vulva and egg. Abbreviata baltazardi represents the first species of Abbreviata Travassos, 1920 reported in China., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants. Methods: A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes. Results: This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect. Conclusions: This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.

Background: β-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking., Aims: This study was to analyze the association between the use of β-blockers and the risk of developing AF., Methods: This nationwide, prospective cohort study utilized data from the 2013-2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group ( n = 2585) and a non-β-blocker treatment group ( n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders., Results: A total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614-3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment., Conclusion: The findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gu, Li, Li, Guo, He, Liu, Gong, Huang and Zhang.)

Species of Baylisascaris (Nematoda: Ascarididae) are of great veterinary and zoonotic significance, owing to cause Baylisascariosis or Baylisascariasis in wildlife, captive animals and humans. However, the phylogenetic relationships of the current 10 Baylisascaris species remain unclear. Moreover, our current knowledge of the detailed morphology and morphometrics of the important zoonotic species B. procyonis is still insufficient. The taxonomical status of B. procyonis and B. columnaris remains under debate. In the present study, the detailed morphology of B. procyonis was studied using light and scanning electron microscopy based on newly collected specimens from the raccoon Procyon lotor (Linnaeus) in China. The results of the ASAP analysis and Bayesian inference (BI) using the 28S, ITS, cox 1 and cox 2 genetic markers did not support that B. procyonis and B. columnaris represent two distinct species. Integrative morphological and molecular assessment challenged the validity of B. procyonis , and suggested that B. procyonis seems to represent a synonym of B. columnaris. Molecular phylogenetic results indicated that the species of Baylisascaris were grouped into 4 clades according to their host specificity. The present study provided new insights into the taxonomic status of B. procyonis and preliminarily clarified the phylogenetic relationships of Baylisascaris species.

Objective: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD)., Methods: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice., Results: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05)., Conclusions: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.

Background: Remnant gastric cancer (GC) is defined as GC that occurs five years or more after gastrectomy. Systematically evaluating the preoperative immune and nutritional status of patients and analyzing its prognostic impact on postoperative remnant gastric cancer (RGC) patients are crucial. A simple scoring system that combines multiple immune or nutritional indicators to identify nutritional or immune status before surgery is necessary., Aim: To evaluate the value of preoperative immune-nutritional scoring systems in predicting the prognosis of patients with RGC., Methods: The clinical data of 54 patients with RGC were collected and analyzed retrospectively. Prognostic nutritional index (PNI), controlled nutritional status (CONUT), and Naples prognostic score (NPS) were calculated by preoperative blood indicators, including absolute lymphocyte count, lymphocyte to monocyte ratio, neutrophil to lymphocyte ratio, serum albumin, and serum total cholesterol. Patients with RGC were divided into groups according to the immune-nutritional risk. The relationship between the three preoperative immune-nutritional scores and clinical characteristics was analyzed. Cox regression and Kaplan-Meier analysis was performed to analyze the difference in overall survival (OS) rate between various immune-nutritional score groups., Results: The median age of this cohort was 70.5 years (ranging from 39 to 87 years). No significant correlation was found between most pathological features and immune-nutritional status ( P > 0.05). Patients with a PNI score < 45, CONUT score or NPS score ≥ 3 were considered to be at high immune-nutritional risk. The areas under the receiver operating characteristic curves of PNI, CONUT, and NPS systems for predicting postoperative survival were 0.611 [95% confidence interval (CI): 0.460-0.763; P = 0.161], 0.635 (95%CI: 0.485-0.784; P = 0.090), and 0.707 (95%CI: 0.566-0.848; P = 0.009), respectively. Cox regression analysis showed that the three immune-nutritional scoring systems were significantly correlated with OS (PNI: P = 0.002; CONUT: P = 0.039; NPS: P < 0.001). Survival analysis revealed a significant difference in OS between different immune-nutritional groups (PNI: 75 mo vs 42 mo, P = 0.001; CONUT: 69 mo vs 48 mo, P = 0.033; NPS: 77 mo vs 40 mo, P < 0.001)., Conclusion: These preoperative immune-nutritional scores are reliable multidimensional prognostic scoring systems for predicting the prognosis of patients with RGC, in which the NPS system has relatively effective predictive performance., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To analyze the effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of PCa cells by regulating the expression of E2F5., Methods: Using real time fluorescence RT-PCR, we detected the expressions of lncRNA SNHG12 and E2F5, constructed the PC3 cells inhibiting the lncRNA SNHG12 expression. After transfection of the PC3 cells, we divided them into an NC, a si-NC, a si-SNHG12, a si-E2F5, a si-SNHG12+OE-si-NC, and a si-SNHG12+OE-E2F5 group, followed by examination of the proliferation, apoptosis, migration and invasiveness of the cells in different groups., Results: The expressions of lncRNA SNHG12 and E2F5 were significantly up-regulated in the PCa tissue compared with those in the adjacent tissue (P < 0.05), remarkably higher in the DU145, LNCaP and PC3 groups than in the RWPE-1 group, the highest in the PC3 group (P < 0.05). The expression of SNHG12 was markedly down-regulated in the si-SNHG12 group (P < 0.05) in comparison with that in the si-NC group, indicating the successful construction of a PC3 cell line interfering with the lncRNA SNHG12 expression. Compared with the si-NC group, the si-SNHG12 group showed significant decreases in the values of CyclinD1, MMP-9 and OD and the numbers of migrating and invading cells, and an increase in apoptotic cells (P < 0.05), while the si-E2F5 group exhibited a remarkably down-regulated expression of E2F5 (P < 0.05), reduced values of CyclinD1, MMP-9 and OD, decreased numbers of migrating and invading cells and an increased number of apoptotic cells (P < 0.05). The dual luciferase report test showed that E2F5 reduced the luciferase activity of SNHG12 (P < 0.05 and had an insignificant impact on the luciferase activity of MUT-SNHG12 (P > 0.05). Inhibiting the expression of lncRNA SNHG12 resulted in significant decreases in the expression of E2F5, values of CyclinD1, MMP-9 and OD and numbers of migrating and invading cells, but an increase in apoptotic cells (P < 0.05). The E2F5 expression, the CyclinD1, MMP-9 and OD values and the numbers of migrating and invading cells were markedly increased while the number of apoptotic cells decreased in the si-SNHG12+OE-E2F5 group compared with those in the si-SNHG12+OE-si-NC group (P < 0.05)., Conclusion: Interfering with the expression of lncRNA SNHG12 can regulate that of E2F5, inhibit the proliferation, migration and invasiveness of PCa cells and promote their apoptosis.

Small molecule inhibitors that target the phosphatidylinositol 3-kinase (PI3K) signaling pathway have received significant interest for the treatment of cancers. The class I isoform PI3Kα is most commonly associated with solid tumors via gene amplification or activating mutations. However, inhibitors demonstrating both PI3K isoform and mutant specificity have remained elusive. Herein, we describe the optimization and characterization of a series of benzoxazepin-oxazolidinone ATP-competitive inhibitors of PI3Kα which also induce the selective degradation of the mutant p110α protein, the catalytic subunit of PI3Kα. Structure-based design informed isoform-specific interactions within the binding site, leading to potent inhibitors with greater than 300-fold selectivity over the other Class I PI3K isoforms. Further optimization of pharmacokinetic properties led to excellent in vivo exposure and efficacy and the identification of clinical candidate GDC-0077 (inavolisib, 32 ), which is now under evaluation in a Phase III clinical trial as a treatment for patients with PIK3CA -mutant breast cancer.

Depression is a high-incidence mental illness that seriously affects human health. AQP4 has been reported to be closely associated with depression, while the underlying mechanism is still unclear. This work aimed to investigate the functional role of AQP4 in depression. Depression mouse model was constructed by administration of chronic social defeat stress (CSDS). We found that AQP4 was highly expressed in the hippocampal tissues of CSDS mice. AQP4 knockdown alleviated depression and enhanced the expression of NR2B and PSD95 in CSDS mice. Moreover, primary hippocampal neurons were treated with N-methyl-d-aspartate (NMDA) to induce neuron injury. AQP4 overexpression repressed cell viability and promoted apoptosis of NMDA-treated primary hippocampal neurons. AQP4 up-regulation repressed the expression of NR2B (surface), and enhanced the expression of NR2B (intracellular), P-NR2B, CaMK II and CK2 in the NMDA-treated primary hippocampal neurons. The influence conferred by AQP4 up-regulation was abolished by KN-93 (CaMK II inhibitor) or TBB (CK2 inhibitor) treatment. Rapamycin treatment enhanced the expression of NR2B (surface), and repressed the expression of AQP4, NR2B (intracellular) and P-NR2B in the primary hippocampal neurons by activating autophagy. The activated autophagy alleviated depression in CSDS mice by repressing AQP4 expression. In conclusion, our data demonstrated that autophagy ameliorated depression by repressing AQP4 expression in mice, and AQP4 knockdown promoted membrane trafficking of NR2B and inhibited phosphorylation of NR2B via CaMK II/CK2 pathway. Thus, our work suggests that AQP4 may be a promising molecular target for the development of antidepressant drugs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock., Methods: This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS., Results: Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05)., Conclusion: Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019., (© 2022. The Author(s).)

Owing to the significant impact of heavy metals in atmospheric deposition on soil, clear knowledge on the present situation and temporal and spatial variation in fluxes of heavy metals in atmospheric deposition all around China is urgently needed. In this study, we collected 99 published papers on deposition fluxes of heavy metals from 2001 to 2021 based on the CNKI and Web of Science database and extracted 718 to 1672 monitoring points from these papers. The Meta-analysis method was used to calculate the weighted average of deposition fluxes of heavy metals, and the spatial-temporal characteristics in different periods from 2000 to 2018 were studied by subgroup analysis, which compared the differences between different types of areas, such as agricultural and rural areas and urban and industrial areas. The results showed that the annual fluxes of heavy metals in atmospheric deposition[mg·(m 2 ·a) -1 ] in China were as follows:Zn (96.75)>Pb (23.37)>Cu (12.77)>Cr (11.04)>Ni (6.61)>As (2.97)>Cd (0.48)>Hg (0.05). Overall, the estimated value of deposition fluxes in China from 2000 to 2018 was higher than that of rural areas in England from 1995 to 1998. The deposition fluxes in industrial areas and urban areas were much higher than those in the agricultural and rural areas, especially the industrial areas where the heavy metal pollution was more serious. The deposition fluxes of As and Cd in the Changsha-Zhuzhou-Xiangtan area were relatively high, whereas the atmospheric deposition of heavy metals in Northeast China, the Pearl River Delta, and North China Plain was more serious than that in the other areas. In the past 20 years, the annual deposition fluxes of Cd fluctuated around the overall average, without an obviously declining trend, whereas the deposition fluxes of Cd in the urban, agricultural, and rural areas showed a trend of growth. These results suggested that precise and risk control measures of atmospheric emissions should be established based on the characteristics of regional industrial structure, which should cover all levels, all types, and all regions. In addition, more restrictive measures should be taken to solve the current problem caused by the higher deposition flux of Cd in atmospheric deposition.

Background and Objective: 101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects., Methods: A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC 0-t ), the area under the plasma concentration-time curve from time zero to infinity (AUC 0-∞ ), the maximum plasma concentration (C max ), the time to maximum plasma concentration (T max ), and the elimination half-life (t 1/2 ). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring., Results: Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median T max of 0.34-0.50 h and eliminated slowly with a mean t 1/2 ranging from 4.29 to 46.76 h for different dose groups. The C max and AUC of 101BHG-D01 increased linearly across the examined dose range of 40-960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study., Conclusions: 101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean C max and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The genus Cissophyllus (Cosmocercoidea: Kathlaniidae) is a rare group of nematodes parasitic in turtles and lizards. To date, only four species have been reported in Asia and North America. However, most of them are inadequately described. The species Cissophyllus leytensis has never been reported since it was originally described by Tubangui and Villaamil in 1933 from the Philippine sailfin lizard Hydrosaurus pustulatus (Eschscholtz, 1829) (Reptilia: Squamata). Furthermore, the systematic status of Cissophyllus/Cissophyllinae in the family Kathlaniidae of the superfamily Cosmocercoidea remains under debate., Methods: The detailed morphology of C. leytensis was studied using light microscopy (LM) and, for the first time, scanning electron microscopy (SEM), based on newly collected specimens from the type host H. pustulatus. Six different genetic markers, including nuclear sequences [small ribosomal subunit (18S), internal transcribed spacer (ITS) and large ribosomal subunit (28S)], plus mitochondrial genes [cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 2 (cox2) and 12S small subunit ribosomal RNA gene] of C. leytensis were sequenced. Additionally, in order to test the validity of the subfamily Cissophyllinae and clarify the phylogenetic relationships of Cissophyllus and the other genera in the family Kathlaniidae, phylogenetic analyses based on 18S + 28S and ITS sequence data were performed using maximum likelihood (ML) and Bayesian inference (BI) analyses, respectively., Results: Our observations using LM and SEM revealed some previously unreported morphological features, necessitating the redescription of this poorly known species. The presence of remarkable morphological variation in the isthmus and the position of excretory pore among different individuals was found. Molecular analysis showed no intraspecific nucleotide divergence detected in the 18S, ITS, 28S, cox2 and 12S regions among different individuals of C. leytensis, but a low level of intraspecific genetic variation was found in the cox1 (0.52%). Our phylogenetic results showed the representatives of the Cosmocercoidea divided into four large clades (Cosmocerca + Aplectana + Cosmocercoides representing the family Cosmocercidae, Cruzia representing the subfamily Cruzinae of Kathlaniidae, Falcaustra + Cissophyllus + Megalobatrachonema representing the subfamily Kathlaniinae of Kathlaniidae, and Orientatractis + Rondonia representing the family Atractidae). The genus Cissophyllus clustered together with the genus Megalobatrachonema in both the ML and BI trees using ITS sequence data, but displayed a sister relationship to the genus Falcaustra in the ML tree and to the genera Falcaustra + Megalobatrachonema in the BI tree using 18S + 28S sequence data., Conclusions: Molecular phylogenetic results further confirmed that the family Kathlaniidae is not a monophyletic group. The subfamily Cruziinae should be moved from the hitherto-defined family Kathlaniidae and elevated as a separate family Cruziidae. The present phylogenetic results also negated the validity of the subfamily Cissophyllinae and supported the genus Cissophyllus assigned in the subfamily Kathlaniinae. Molecular analysis indicated that the morphological variation in the isthmus and position of excretory pore among different individuals should be considered as intraspecific variation. Moreover, some characters important for the specific diagnosis of C. leytensis are reported for the first time: the number of acuminate denticles (lamellae) on each lip, the chitinized pharynx with three flabellate pharyngeal plates, the presence of single medioventral precloacal papilla and the detailed morphology of caudal papillae. The present study is only the second record of C. leytensis., (© 2022. The Author(s).)

Paraleptus (Spirurida: Physalopteridae) is a small genus of nematodes, parasitic in fishes, most species of which are inadequately described. Genetic data for these congeners have not been reported. The detailed morphology of P. chiloscyllii was studied using light and scanning electron microscopy, based on newly collected specimens from the brownbanded bambooshark C. punctatum Müller & Henle (Elasmobranchii: Orectolobiformes) in the Taiwan Strait. Some previously unreported morphological features of taxonomic significance were observed, i.e., pseudolabium with two sublateral rows of 6-7 small spines, 7-8 small spines on each lower rim between pseudolabia, deirids not distally bifurcated, vulva with remarkable protruding lip, presence of 1 pair medio-ventral precloacal papillae and 1 pair of discoid protrusions of postcloacal lip in male. The specimens described by González-Solís & Ali's (2015) as P. chiloscyllii from the Arabian carpetshark C. arabicum off Iraq are considered a new species, for which the name P. moraveci n. sp. is proposed. The genetic characterization of the partial small (18S) and large (28S) ribosomal DNA, and the partial mitochondrial cytochrome c oxidase subunit 1 (cox1) of P. chiloscyllii are provided for the first time. There was no intraspecific nucleotide divergence detected in the 18S and 28S regions among different individuals of P. chiloscyllii, but a low level of intraspecific genetic variation was found in the cox1 (0.62-0.92%). The present genetic data is very important for molecular identification, and will be valuable for further invertigantions on the population genetics and phylogeny of this group., (Copyright © 2021. Published by Elsevier B.V.)

The nuclear factor kappa B (NF-κB) pathway and inhibitor of NF-κB kinase β (IKKβ) are involved in Alzheimer disease (AD) pathogenesis. This study explored the mechanisms underlying IKKβ-mediated Aβ aggregation and neuron regeneration in APP.PS1 mice. Adenoviral transduction particles were injected into the hippocampal CA1 region of the mice to knock down or inhibit target genes. Morris water maze was performed to evaluate the cognitive function of the mice. Aβ deposition was determined by histological examination. sh-IKKβ plasmids and microRNA (miR)-155-5p inhibitor were transfected into Aβ1-42-induced N2a cells. The expressions of AD-related proteins were detected by Western blot. The interaction between S-phase kinase-associated protein 2 (SKP2) and IKKβ was assessed by co-immunoprecipitation. IKKβ knockdown (KD) and miR-155-5p inhibition ameliorated cognitive impairment, improved neuron regeneration, and attenuated Aβ deposition in APP/PS1 mice. SKP2 KD aggravated cognitive impairment, inhibited neuron regeneration, and promoted Aβ deposition in the mice. SKP2 regulated the stability of IKKβ protein via ubiquitination. MiR-155-5p regulates Aβ deposition and the expression of Aβ generation-related proteins in N2a cells via targeting SKP2. These results indicate that the miR-155-5p/SKP2/IKKβ axis was critical for pathogenesis in this AD model and suggest the potential of miR-155-5p as a target for AD treatment., (© 2021 American Association of Neuropathologists, Inc. All rights reserved.)

The synthesis of lightweight yet strong-ductile materials has been an imperative challenge in alloy design. In this study, the CoCrNi-based medium-entropy alloys (MEAs) with added Al and Si were manufactured by vacuum arc melting furnace subsequently followed by cool rolling and anneal process. The mechanical responses of CoCrNiAl 0.1 Si 0.1 MEAs under quasi-static (1 × 10 -3 s -1 ) tensile strength showed that MEAs had an outstanding balance of yield strength, ultimate tensile strength, and elongation. The yield strength, ultimate tensile strength, and elongation were increased from 480 MPa, 900 MPa, and 58% at 298 K to 700 MPa, 1250 MPa, and 72% at 77 K, respectively. Temperature dependencies of the yield strength and strain hardening were investigated to understand the excellent mechanical performance, considering the contribution of lattice distortions, deformation twins, and microbands. Severe lattice distortions were determined to play a predominant role in the temperature-dependent yield stress. The Peierls barrier height increased with decreasing temperature, owing to thermal vibrations causing the effective width of a dislocation core to decrease. Through the thermodynamic formula, the stacking fault energies were calculated to be 14.12 mJ/m 2 and 8.32 mJ/m 2 at 298 K and 77 K, respectively. In conclusion, the enhanced strength and ductility at cryogenic temperature can be attributed to multiple deformation mechanisms including dislocations, extensive deformation twins, and microbands. The synergistic effect of multiple deformation mechanisms lead to the outstanding mechanical properties of the alloy at room and cryogenic temperature.

Abnormalities in CD4 + T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve's effect on differentiation of CD4 + T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4 + T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4 + T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4 + T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4 + T cells. The CD4 + T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4 + T cell differentiation in response to VMC.

Cosmocercoid nematodes are common parasites in the digestive tract of amphibians. However, our knowledge of the species diversity, genetic data and molecular phylogeny of the superfamily Cosmocercoidea are far from being well understood. In the present study, large numbers of cosmocercoid nematodes were collected from the fine-spined frog Sylvirana spinulosa (Smith) (Anura: Ranidae) and the white-spotted thigh tree-frog Polypedates megacephalus (Hallowell) (Anura: Rhacophoridae) in Guangxi Province, China. Integrated morphological and genetic evidence reveals these nematode specimens to be a new species of the genus Aplectana, A. dayaoshanensis n. sp. (Cosmocercoidea: Cosmocercidae). The molecular characterization of small ribosomal DNA (18S), internal transcribed spacer (ITS) and large ribosomal DNA (28S) of A. dayaoshanensis n. sp., together with the 28S of A. chamaeleonis (Baylis, 1929) (collected from Hyperolius kivuensis Ahl in Rwanda), were reported for the first time. Moreover, phylogenetic analyses using maximum likelihood (ML) inference based on 18S + 28S and ITS sequence data, respectively, both supported the family Cosmocercidae to be a monophyletic group and the family Kathlaniidae to be a paraphyletic group. Our phylogenetic results rejected the monophyly of the genus Aplectana. The present results contribute to the knowledge of the species diversity and genetic data of cosmocercoid nematodes, and preliminarily revealed the phylogenetic relationships of the major families and some genera in the Cosmocercoidea., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

In order to explore the concentrations of heavy metals and the influence of fencing on Hongze lake, the content, source, and spatial distribution characteristics of heavy metals in surface sediments and ecological risks were analyzed in 2018 after part of the fence around Hongze Lake was removed. The results showed that the average contents of Cr, Ni, Cu, Zn, As, Cd, and Pb in the surface sediments in Hongze Lake were 66.78, 33.89, 25.35, 74.77, 16.55, 0.23, and 27.20 mg·kg -1 , respectively. Cr, Ni, Cu, Zn, and Pb contents were at non-polluting levels, with As and Cd at the lowest level, based on the accumulation index evaluation. Except for Cd, all the elements showed low potential ecological risk. The results showed that the heavy metal content in the fenced, dismantled, and peripheral areas increased and accumulated towards the center of the lake. The removal of the fence did not significantly reduce the heavy metal content in the short-term. Overall, Hongze Lake presented a state of low ecological risk. In the future, environmental policies should include surface sediment accumulation areas and fencing culture in the north and northeast of Hongze Lake.

Objective: To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors. Methods: The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management. Results: Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed. Conclusion: Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.

Background: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China., Methods: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD., Results: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05)., Conclusion: Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Nematodes of the family Cosmocercidae (Ascaridomorpha: Cosmocercoidea) are mainly parasitic in the digestive tract of various amphibians and reptiles worldwide. However, our knowledge of the molecular phylogeny of the Cosmocercidae is still far from comprehensive. The phylogenetic relationships between Cosmocercidae and the other two families, Atractidae and Kathlaniidae, in the superfamily Cosmocercoidea are still under debate. Moreover, the systematic position of some genera within Cosmocercidae remains unclear., Methods: Nematodes collected from Polypedates megacephalus (Hallowell) (Anura: Rhacophoridae) were identified using morphological (light and scanning electron microscopy) and molecular methods [sequencing the small ribosomal DNA (18S), internal transcribed spacer 1 (ITS-1), large ribosomal DNA (28S) and mitochondrial cytochrome c oxidase subunit 1 (cox1) target regions]. Phylogenetic analyses of cosmocercoid nematodes using 18S + 28S sequence data were performed to clarify the phylogenetic relationships of the Cosmocercidae, Atractidae and Kathlaniidae in the Cosmocercoidea and the systematic position of the genus Aplectana in Cosmocercidae., Results: Morphological and genetic evidence supported the hypothesis that the nematode specimens collected from P. megacephalus represent a new species of Aplectana (Cosmocercoidea: Cosmocercidae). Our phylogenetic results revealed that the Cosmocercidae is a monophyletic group, but not the basal group in Cosmocercoidea as in the traditional classification. The Kathlaniidae is a paraphyletic group because the subfamily Cruziinae within Kathlaniidae (including only the genus Cruzia) formed a seperate lineage. Phylogenetic analyses also showed that the genus Aplectana has a closer relationship to the genus Cosmocerca in Cosmocercidae., Conclusions: Our phylogenetic results suggested that the subfamily Cruziinae should be moved from the hitherto-defined family Kathlaniidae and elevated as a separate family, and the genus Cosmocerca is closely related to the genus Aplectana in the family Cosmocercidae. The present study provided a basic molecular phylogenetic framework for the superfamily Cosmocercoidea based on 18S + 28S sequence data for the first time to our knowledge. Moreover, a new species, A. xishuangbannaensis n. sp., was described using integrative approach.

It has been demonstrated Inhibitor Kappa B Kinase β (IKKβ) facilitates autophagy, which in turn mediates p-Tau protein clearance. However, the specific regulatory mechanism in Alzheimer's disease (AD) remains unclear. Firstly, AD model was generated by the intracerebroventricular (ICV) injection of the Β-amyloid 1-42 (Aβ 1-42 ) peptide. Subsequently, mice were injected with shRNA adenoviral transduction particles designed to target DJ-1 or Aβ 1-42 or Aβ 1-42  + shNC or Aβ 1-42  + shRNA against DJ-1. shRNA against DJ-1 were injected into hippocampus of mice (8 × 10 4 viral particles for each mice) for seven consecutive days. Immunohistochemistry was performed to detect the accumulation of Aβ in the hippocampus of mice, and Hematoxylin-Eosin (HE) staining assay was carried to detect pathological changes in the hippocampus of mice. Further, sh-IKKβ, shDJ-1, pcDNA-IKKβ and pcDNA-DJ-1 plasmids were transfected into HT-22 cells, MTT assay, TUNEL staining and Hoechst staining were performed to detect cell viability and apoptosis, respectively. Western blotting was carried to measure the relative expression of proteins. Findings indicated that Aβ 1-42 inhibited autophagy and up-regulated p-Tau protein expression; Overexpression of IKKβ and DJ-1 all rescued the autophagy inhibited by Aβ 1-42 and down-regulated p-Tau protein expression induced by Aβ 1-42 ; DJ-1 up-regulated IKKβ via p-VHL, further promoted autophagy and reduced the expression of p-Tau protein; DJ-1 knockdown inhibited autophagy and up-regulated p-Tau protein expression, resulting in delayed behavior in mice. In conclusion, IKKβ, modulated by DJ-1/p-VHL, reduces p-Tau accumulation via autophagy in AD's disease model. This study may provide theoretical basis for the treatment of AD., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock., Methods: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes., Results: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA., Conclusion: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

Microglia polarization is associated with the pathogenesis of depression. A previous study shows that long non-coding RNA uc.80- is down-regulated in the hippocampus of depressed rats. Thus, this article aims to investigate the role of uc.80- in microglia polarization in depression. We first established depression model rats by chronic unpredictable mild stress (CUMS) regiment. We found that hippocampus of depressed rats exhibited an increase of M1 microglias and a decrease of M2 microglias. uc.80- was down-regulated in hippocampus of depressed rats. Furthermore, the detection of behaviouristics of depressed rats showed that uc.80- overexpression alleviated depression of rats. In addition, uc.80- overexpression promoted M2 polarization of microglias in vivo and in vitro. uc.80- overexpression led to a decrease in apoptosis of hippocampal neurons in vivo and in vitro. In conclusion, our study confirms that lncRNA uc.80- overexpression ameliorates depression in rats by promoting M2 polarization of microglias. Thus, our work suggests that uc.80- may be a target gene for depression treatment., (© 2020 International Union of Biochemistry and Molecular Biology.)

Ethnopharmacological Relevance: "Xiaoerhuashi Pill, XP", with a history of 30 years in China, was included in the first part of the 2015 edition of the Chinese Pharmacopoeia and is widely used in the treatment for pediatric diseases in clinical application. Its main indications include the accumulation of heat caused by food stagnation in children, which has the effect of digestive stagnation and purge heat to relax the bowels., Aim of the Study: High-calorie diet, closely related to the occurrence and development of multiple diseases, is an unhealthy status of life. However, there is no effective intervention in clinic. Thus, based on animal experiments and bioinformatics, this study aims to explore the potential mechanisms of action of Chinese patent medicine- "Xiaoerhuashi Pill, XP" in the intervention of high-calorie diet., Materials and Methods: A high-calorie diet model was prepared by 3-week-old rats. The defecation and intestinal mucosal morphology were observed after intragastric administration of "Xiaoerhuashi Pill, XP". The components of "Xiaoerhuashi Pill, XP" were obtained by chromatography-mass spectrometry, with the corresponding targets obtained by database and target fishing. The key effects substances were obtained by molecular docking, with the obtaining of the ore pathway of "Xiaoerhuashi Pill, XP" in intervention of high-calorie diet based on the enrichment analysis., Results: "Xiaoerhuashi Pill, XP" can actively interfere with defecation and intestinal mucosal structures in high-calorie diet animals. A total of 37 substances were identified in the pediatric digestion solution, and 356 target proteins were mapped, 25 of which were associated with a high-calorie diet. Overall, the analysis shows that the highest degree of integration was quercetin and PON1 protein, with the highest enrichment of insulin resistance pathway., Conclusion: "Xiaoerhuashi Pill, XP" can intervene in the health status of high-calorie diet animals. Integration of quercetin and PON1 protein can regulate lipid levels, which may be the key mechanisms of action in "Xiaoerhuashi Pill, XP". The mechanisms, more specifically, may be related to the regulation of pancreas islet function, thus providing a reference for the clinical application of "Xiaoerhuashi Pill, XP", clinical intervention of high-calorie diet and new drug development., Competing Interests: Declaration of competing interest The authors declare that no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper are involved., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Statement of Problem: Residual cement is detrimental to the long-term success of dental implants with a cement-retained restoration. The complete elimination of excess cement remains a challenge., Purpose: The purpose of this in vitro study was to evaluate the effects of precementation technique on minimizing the residual cement and retention of restorations., Material and Methods: Four custom cobalt-chromium alloy (Co-Cr) abutments were manufactured by computer-aided design and computer-aided manufacturing (CAD-CAM) as precementation abutments with height and radius reductions of 25 μm (A25), 50 μm (A50), 75 μm (A75), and 100 μm (A100). Fifty CAD-CAM-fabricated standard Co-Cr abutments and corresponding crowns were randomly matched and treated as follows: 10 specimens were cemented with the conventional cementation procedure with glass ionomer cement (G0), and 40 were precemented with precementation abutments (n=10) before the definitive cementation with standard abutments (G25, G50, G75, G100). The weight of the cement in the cement space was calculated, and the marginal sealing was evaluated by using a stereoscopic microscope. The effects of precementation with resin cement on minimizing residual cement around the marginal area of dental implants were further evaluated extraorally. The influence of precementation with glass ionomer and resin cement on the retention force was analyzed by using a universal testing machine at a crosshead speed of 0.5 mm/min. One-way ANOVA was used to analyze cement mass and marginal sealing values. Two-way ANOVA was used to compare the retention forces (α=.05)., Results: The cement weight of G50 (7.2 ±0.6 mg) was significantly higher than that of G25 (6.0 ±1.1 mg, P<.05), while no significant differences in cement weights were found among G50, G75, and G100. Consistently, the G50, G75, and G100 had higher marginal sealing values than that of the G25 (P<.01). Extraoral experiments showed that the precementation with A50 reduced subgingival residual cement without affecting retention., Conclusions: These in vitro results suggest that precementation with a precisely manufactured precementation abutment minimized the residual cement around implant abutments, and 50 μm could be a preferable precementation space., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Biological thiols including homocysteine (Hcy), cysteine (Cys), hydrogen sulfide (H 2 S) and glutathione (GSH) play crucial roles in various pathological and physiological processes. The development of optical probes for biothiols has been an active research area in recent years. Herein, a new turn-on fluorescence probe (HD-NBD) was designed and synthesized by fusing tetrahydro[5]helicene and 7-nitro-2,1,3-benzoxadiazole (NBD) for simultaneous discrimination of Hcy/Cys, H 2 S and GSH in aqueous solution. This probe is able to show unique absorbance enhancement at 548 nm for H 2 S and additional fluorescence enhancement at 536 nm only for Cys/Hcy, which can be used to discriminate H 2 S, Cys/Hcy and GSH simultaneously. In addition, HD-NBD also shows low background without any self-fluorescence, as well as high selectivity toward common biothiols. The low detection limits of this probe are about 0.15 μM for Hcy with a wide linear range (1-80 μM), 0.36 μM for Cys (linear range: 1-45 μM), 0.79 μM for H 2 S (linear range: 1-80 μM) and 4.44 μM for GSH (linear range: 1-60 μM). Moreover, HD-NBD can identify Hcy/Cys, H 2 S from GSH and other amino acids with high sensitivity and selectivity, therefore it could be used for detecting endogenous and exogenous Hcy/Cys under biological condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To investigate the distribution, source, and ecological risk of organochlorine pesticides (OCPs) residues in Lake Gucheng, surface water, sediment, and biological samples were collected from 12 sampling sites of Lake Gucheng and its inlets and outlets during summer and winter, and the concentrations of 19 OCPs were analyzed. The results showed that the concentration (dry weight) of OCPs in Lake Gucheng ranged from 26.74 to 48.12 ng·L -1 in surface water, 9.01 to 35.34 ng·g -1 in sediment, and 13.39 to 124.29 ng·g -1 in organisms. The pollution characteristics of OCPs in surface water showed that the concentration was much higher in summer than in winter, and much higher at inflow and outflow rivers than in farming ponds and the central region of Lake Gucheng; the seasonal pollution characteristics in sediment were not obvious. All 19 kinds of OCPs in water, sediment, and organisms were detected in different degrees, and the dominant contaminants were HCHs and DDTs. α -HCH was the main pollutant at all sites in both surface water and sediment, with 21% to 42% of total HCHs in two seasons. p,p '-DDD was the main pollutant in surface water with 30% to 76% of total DDTs, whereas p,p '-DDT was the main pollutant in sediment with 68% to 93% of total DDTs in two seasons. Source analysis based on ratios of HCHs isomers and DDTs isomers indicated that there was a new input of OCPs under anaerobic conditions in the study area. The ecological risk assessment showed that the OCPs in surface water did not lead to significant health risks, but the OCPs in sediments might pose ecological risks to the Lake Gucheng ecosystem. The organisms were within the acceptable potential carcinogenic risk range.

Establishing a stable resin-dentin hybrid layer is an effective method to improve the adhesion durability of the restoration. The biomodification of dentin by cross-linkers can enhance the mechanical properties of collagen and resistance to enzymatic hydrolysis while, inhibiting the process of demineralization and promoting the remineralization of dentin, which has the potential clinical applicability of preventing dental caries and improving adhesive property. This review summarizes the biomodification of dentin type Ⅰ collagen by different cross-linkers.

Glial cell line-derived neurotrophic factor (GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain, α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α- and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level, β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level, α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats (SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α- and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016., Competing Interests: None

Background: Abernethy malformation is a rare congenital abnormality. Imaging examination is an important method for the diagnosis. The purpose of this study was to demonstrate manifestations of multi-slice computed tomography (MSCT) in Abernethy malformation and its diagnostic accuracy., Methods: Fourteen children with Abernethy malformation were admitted to our center in China between July 2011 and January 2018. All 14 patients (eight males and six females) received MSCT and digital subtraction angiography (DSA) while eight patients also received ultrasound. The patients' age ranged from 1 to 14 (median age 8 years old). The clinical records of the patients were retrospectively reviewed. MSCT raw data were transferred to an Advantage Windows 4.2 or 4.6 workstation (General Electric Medical Systems, Waukesha, WI). We compared the findings of MSCT with DSA and surgical results in order to ascertain diagnostic accuracy., Results: Three cases had type Ib Abernethy malformation and eleven cases had type II. Two cases of type II Abernethy malformation were misdiagnosed as type Ib using MSCT. Comparing the findings of MSCT with DSA and surgical results, the accuracy of MSCT was 85.7% (12/14), in which 100.0% (3/3) were type Ib and 81.8% (9/11) were type II. Clinical information included congenital heart disease, pulmonary hypertension, diffuse pulmonary arteriovenous fistula, abnormal liver function, hepatic nodules, elevated blood ammonia, and hepatic encephalopathy. Eleven cases were treated after diagnosis. One patient with Abernethy malformation type Ib (1/3) underwent liver transplantation. Seven patients with Abernethy malformation type II (7/11) were treated by shunt occlusion, received laparoscopy, or were treated with open surgical ligation. Another three patients (3/11) with Abernethy malformation type II were treated by interventional portocaval shunt occlusion under DSA., Conclusion: MSCT attains excellent capability in diagnosing type II Abernethy malformation and further shows the location of the portocaval shunt. DSA can help when it is hard to determine diagnosis between Abernethy type Ib and II using MSCT.

Objective: To evaluate clinical and radiological outcomes of proximal femoral nail anti-rotation (PFNA-II) devices and demonstrate the effectiveness of PFNA-II for the treatment of basicervical fractures in elderly patients., Methods: A retrospective review of all patients treated with PFNA-II for a proximal femoral fracture between January 2013 and February 2017 at three different institutions (Shanghai General Hospital, Shanghai Punan Hospital and Shanghai Seventh People's Hospital) was conducted. The X-ray films were strictly reviewed by three trauma surgeons and a professional radiology doctor. Patients over 60 years of age who met the following criteria were included: (i) sustained low-energy trauma; (ii) a two-part fracture; (iii) fracture line located at the base of the femoral neck and that was medial to the intertrochanteric line and exited above the lesser trochanter but was more lateral than a classic transcervical fracture. Follow-up time should be longer than 6 months. A total of 52 patients who met the inclusion criteria were selected. The average age at diagnosis was 75.1 years (range, 63-91 years); 13 patients were men and 39 were women. The same proximal femoral nail anti-rotation devices and the same surgical procedures were applied to all patients. Postoperative radiographic union time and modified Harris hip scores were used as major indicators for evaluating the effectiveness of surgery., Results: The average follow-up period was 22.5 months (18.5, 23.9, and 21.2 months, respectively) and radiographic unions were observed at an average of 19.6 weeks (range, 12-28 weeks). The patients were evaluated immediately after surgery, as well as 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Of the 49 patients, 38 had good reduction qualities (75.5%), 9 acceptable (18.3%), and 3 poor (6.1%). Radiographic union was confirmed in all fractures at an average of 19.6 weeks (range, 12-28 weeks). The mean Harris hip score was 84.9 (range, 65-99): excellent in 9 patients (18.36%), good in 30 (61.22%), medium in 8 (16.32%), and poor in 2 (4.08%). Slight persistent pain occurred in 3 patients, but these patients could still walk with the help of a cane. Two patients had symptoms of excessive telescoping. Eight patients experienced postoperative medical complications, mainly pneumonia and urinary tract infection., Conclusion: Based on the clinical and radiological outcomes, the PFNA-II devices provide strong rotational stability and excellent clinical prognosis, and are an appropriate treatment option for basicervical proximal femoral fracture in elderly patients., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Purpose: To compare the time return to work and long-term results of tendoscopic versus open technique for de Quervain's disease., Methods: From 2005 to 2013, either tendoscopic or open decompression was performed on 56 consecutive patients (56 wrists) with symptomatic de Quervain's disease despite a minimum of 3 months non-operative treatment. Of the 50 patients who met the inclusion criteria, 41 patients were followed-up for a mean of 7.21 years postoperatively. Among these 41 wrists, 20 underwent tendoscopic release (group A), and 21 underwent open release (group B). The clinical evaluations were performed preoperatively, 1 month postoperatively and at last follow-up visit, using visual analog scale (VAS); the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome score; and the Finkelstein's test. The Patient and Observer Scar Assessment Scale (POSAS) was used as an esthetic evaluation tool of the scar at last follow-up., Results: No significant baseline differences were found between two groups. The average time return to work in group A was less than in group B (P < 0.05), The mean VAS and DASH scores improved significantly in both groups at 1 month and last follow-up visit (P < 0.001). At 1 month, the scores in group A were significantly better than in group B (P < 0.05 and P < 0.001, respectively). There was no difference between groups at last follow-up. In addition, the improvement of the mean DASH score was significantly greater in group A than in group B (34.74 ± 10.99 in group A and 23.58 ± 12.01 in group B, P < 0.01) at 1 month. For POSAS scale, both the OSAS and PSAS scores were significantly better in group A. One patient in group A had cephalic vein injury and 3 patients in group B was involved with radial sensory nerve injury. All patients showed negative on Finkelstein's test at last follow-up., Conclusions: The results of this study suggest that tendoscopic technique for de Quervain's disease could provide earlier symptom relief and earlier recovery with fewer complications and more desirable scar, as well as equivalent successful long-term outcome, when compared with traditional open release technique.