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Importance: Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD., Objective: To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery., Design, Setting, and Participants: This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible., Interventions: Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 μg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively., Main Outcomes and Measures: The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis., Results: All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02)., Conclusions and Relevance: Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.

Objective: Increasing researches supported that intravenous ketamine/esketamine during the perioperative period of cesarean section could prevent postpartum depression(PPD). With the effective rate ranging from 87.2 % to 95.5 % in PPD, ketamine/esketamine's responsiveness was individualized. To optimize ketamine dose/form based on puerpera prenatal characteristics, reducing adverse events and improving the total efficacy rate, prediction models were developed to predict ketamine/esketamine's efficacy., Method: Based on two randomized controlled trials, 12 prenatal features of 507 women administered the ketamine/esketamine intervention were collected. Traditional logistics regression, SVM, random forest, KNN and XGBoost prediction models were established with prenatal features and dosage regimen as predictors., Results: According to the logistic regression model (a in  = 0.10, a out  = 0.15, area under the receiver operating characteristic curve, AUC = 0.728), prenatal Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, thoughts of self-injury and bad mood during pregnancy were associated with poorer ketamine efficacy in PPD prevention, whilst a high dose of esketamine (0.25 mg/kg loading dose+2 mg/kg PCIA) was the most effective dosage regimen and esketamine was more recommended rather than ketamine in PPD. The AUC validation set of KNN and XGBoost model were 0.815 and 0.651, respectively., Conclusion: Logistic regression and machine learning algorithm, especially the KNN model, could predict the effectiveness of ketamine/esketamine iv. during the course of cesarean section for PPD prevention. An individualized preventative strategy could be developed after entering puerpera clinical features into the model, possessing great clinical practice value in reducing PPD incidence., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery., Method: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration., Results: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05)., Conclusion: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Chloramphenicol (CAP), an antimicrobial drug that is widely used in animal feed, would have a negative effect on human health due to its low elimination rate and relatively high residue in animal food. It is important to develop a rapid and economic method to determine CAP in animal food to ensure that human health is not affected., Results: A new fluorescence immunochromatography strip was developed and established for the detection of CAP residue in chicken muscles for the first time. A CAP-bovine serum albumin conjugate, monoclonal antibody and polyclonal antibody against CAP were applied to constitute a fluorescence immunochromatography strip. The fluorescence intensity was detected by a charge-coupled device scanner and transformed to a digital value. The CAP linearity working range was from 0.1 ng mL(-1) to 20 ng mL(-1) with a limit of detection of 0.1 ng mL(-1) within 10 min. The performance of the strip assay was compared with a commercial ELISA kit and the correlation coefficient was 0.99, which indicated that the new strip assay had a good quantification ability for CAP., Conclusion: The fluorescence immunochromatography strip was successfully applied to the detection of CAP residues in chicken samples. To our knowledge, it is the first report regarding the development of a fluorescence immunochromatography method for screening CAP in animal samples., (© 2013 Society of Chemical Industry.)

The aetiological agent of an emergent outbreak of atypical pneumonia, severe acute respiratory syndrome (SARS), is a positive-stranded RNA virus (SARS-CoV) belonging to the Coronaviridae family with a genome that differs substantially from those of other known coronaviruses. Highly conserved heptad-repeat (HR1 and HR2) regions in class I viral fusion proteins, including spike protein from SARS coronavirus, interact with each other to form a six-helix bundle, which is called a fusion core. The crystal structure of the fusion core is expected to greatly facilitate drug design. Crystals of the fusion core of SARS-CoV spike protein have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 A resolution at 100 K in-house. The crystals have unit-cell parameters a = 121.2, b = 66.3, c = 70.0 A, alpha = gamma = 90, beta = 107.4 degrees and belong to space group C2. Assuming the presence of six molecules per asymmetric unit, the solvent content is estimated to be about 28%.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a newly emergent virus responsible for a worldwide epidemic in 2003. The coronavirus spike proteins belong to class I fusion proteins, and are characterized by the existence of two heptad repeat (HR) regions, HR1 and HR2. The HR1 region in coronaviruses is predicted to be considerably longer than that in other type I virus fusion proteins. Therefore the exact binding sequence to HR2 from the HR1 is not clear. In this study, we defined the region of HR1 that binds to HR2 by a series of biochemical and biophysical measures. Subsequently the defined HR1 (902-952) and HR2 (1145-1184) chains, which are different from previously defined binding regions, were linked together by a flexible linker to form a single-chain construct, 2-Helix. This protein was expressed in Escherichia coli and forms a typical six-helix coiled coil bundle. Highly conserved HR regions between mouse hepatitis virus (MHV) and SARS-CoV spike proteins suggest a similar three-dimensional structure for the two fusion cores. Here, we constructed a homology model for SARS coronavirus fusion core based on our biochemical analysis and determined the MHV fusion core structure. We also propose an important target site for fusion inhibitor design and several strategies, which have been successfully used in fusion inhibitor design for human immunodeficiency virus (HIV), for the treatment of SARS infection.

Membrane fusion between virus and host cells is the key step for enveloped virus entry and is mediated by the viral envelope fusion protein. In murine coronavirus, mouse hepatitis virus (MHV), the spike (S) protein mediates this process. Recently, the formation of anti-parallel 6-helix bundle of the MHV S protein heptad repeat (HR) regions (HR1 and HR2) has been confirmed, implying coronavirus has a class I fusion protein. This bundle is also called fusion core. To facilitate the solution of the crystal structure of this fusion core, we deployed an Escherichia coli in vitro expression system to express the HR1 and HR2 regions linked together by a flexible linker as a single chain (named 2-helix). This 2-helix polypeptide subsequently assembled into a typical 6-helix bundle. This bundle has been analyzed by a series of biophysical and biochemical techniques and confirmed that the design technique can be used for coronavirus as we successfully used for members of paramyxoviruses.

Crystals of a 2-Helix fusion-core construct of MHV spike protein (commonly referred to as E2) have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.8 A resolution at 100 K in-house. Furthermore, a selenomethionine (SeMet) derivative of MHV spike protein fusion core has been overexpressed and purified. The derivative crystals were obtained under similar conditions and three different wavelength data sets were collected to 2.4 A resolution from a single derivative crystal at BSRF (Beijing Synchrotron Radiation Facility). The crystals have unit-cell parameters a = b = 48.3, c = 199.6 A, alpha = beta = 90, gamma = 120 degrees and belong to space group R3. Assuming the presence of two molecules in the asymmetric unit, the solvent content is calculated to be about 46%.

The surface transmembrane glycoprotein is responsible for mediating virion attachment to cell and subsequent virus-cell membrane fusion. However, the molecular mechanisms for the viral entry of coronaviruses remain poorly understood. The crystal structure of the fusion core of mouse hepatitis virus S protein, which represents the first fusion core structure of any coronavirus, reveals a central hydrophobic coiled coil trimer surrounded by three helices in an oblique, antiparallel manner. This structure shares significant similarity with both the low pH-induced conformation of influenza hemagglutinin and fusion core of HIV gp41, indicating that the structure represents a fusion-active state formed after several conformational changes. Our results also indicate that the mechanisms for the viral fusion of coronaviruses are similar to those of influenza virus and HIV. The coiled coil structure has unique features, which are different from other viral fusion cores. Highly conserved heptad repeat 1 (HR1) and HR2 regions in coronavirus spike proteins indicate a similar three-dimensional structure among these fusion cores and common mechanisms for the viral fusion. We have proposed the binding regions of HR1 and HR2 of other coronaviruses and a structure model of their fusion core based on our mouse hepatitis virus fusion core structure and sequence alignment. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation may be applied to the inhibition of a number of emerging infectious diseases, including severe acute respiratory syndrome.

Highly conserved heptad-repeat (HR1 and HR2) regions in class I viral fusion (F) proteins, including the F protein from paramyxovirus, interact with each other post-fusion to form a six-helix bundle called a fusion core. Crystals of the fusion core of Nipah virus have been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.1 angstroms resolution at 100 K in-house. The crystals have unit-cell parameters a = 31.664, b = 31.725, c = 51.256 angstroms, alpha = 80.706, beta = 86.343, gamma = 65.812 degrees and belong to space group P1. Crystals of the fusion core of Hendra virus have also been grown at 291 K using PEG 4000 as precipitant. The diffraction pattern of the crystal extends to 2.0 angstroms resolution at 100 K in-house. A selenomethionine (SeMet) derivative of the HeV fusion core was overexpressed using the same Escherichia coli expression system and purified. The derivative crystals were obtained under similar conditions and three different wavelength data sets were collected to 2.0 angstroms resolution from the derivative crystal at BSRF (Beijing Synchrotron Radiation Facility). The crystals have unit-cell parameters a = 31.997, b = 31.970, c = 53.865 angstroms, alpha = 85.990, beta = 85.842, gamma = 68.245 degrees and belong to space group P1., (Copyright 2004 International Union of Crystallography)