ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective:To construct a structured education course for patients with neurogenic bladder during the rehabilitation period.Methods:This study consisted three stages of current situation survey, literature search, and expert consultation. From February 2022 to February 2023, a current survey was conducted on the self-management needs of 62 patients with neurogenic bladder. In April 2023, a literature search was conducted to summarize the best evidence on nursing and management of neurogenic bladder, and form the initial version of course indicators and content. From April to May 2023, 14 experts were selected for consultation, and the Delphi method was used to demonstrate the course indicators and content, and to construct the final draft of the course.Results:A total of 62 patients with neurogenic bladder were included, they have requirements for water management, bladder function training, and dietary requirements, etc. A total of 2 053 articles were retrieved, and 14 articles were ultimately included, including eight guidelines, four evidence summaries, one expert consensus, and one systematic review. The expert authority coefficients for the two rounds of expert consultation were 0.93 and 0.92, respectively. The Kendall coordination coefficient of various indicators in the second round of expert consultation was 0.227 to 0.288 ( P<0.01). After two rounds of expert consultation, a structured education course for patients with neurogenic bladder during the rehabilitation period was finally developed, including six primary indicators, 21 secondary indicators, and 30 tertiary indicators. Conclusions:The structured education course for patients with neurogenic bladder during the rehabilitation period, based on current situation survey, high-quality evidence, and expert consultation, is comprehensive in content and reasonably designed, which can provide supportive assistance for future nursing health education and management for patients with neurogenic bladder.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC 0–24h /MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E max (Hill) equation. The dose was calculated based on the AUC 0–24h /MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. suis infections.

Objective We aim to evaluate and discuss the feasibility of Hyaline imaging of three-dimension sonography in observation of paravaginal support structure in normal nonporous women.Methods Total of 45 normal infertile women were chosen.Three-dimensional volume datasets were collected at rest by transperineal ultrasound.The three-dimensional Hyaline images were acquired off-line.We observed the morphologic features of paravaginal support structure on the axial plane in middle vagina and measured the anteroposterior and lateral horizontal distances between bilateral paravaginal support structure and ureter.The consistency between two sonographers were analyzed by intraclass correlation coefficient (ICC).Results In three-dimensional Hyaline imaging sonogram,paravaginal support structure was appeared as typically tenting-like shaped.The anteroposterior distances between paravaginal support structure and center of ureter were listed as followed:left (-0.31 ± 1.29) mm,right (0.47 ± O.99) mm.While the lateral horizontal distances were left (12.67 ± 6.70) mm,right (13.01 ± 5.75) mm.There were no statistical differences between bilateral both anteroposterior and lateral horizontal distances.The consistency between two sonographers for distinguishing paravaginal support structure on the middle-vaginal plane and measuring distances between paravaginal support structure and center of ureter was remarkably high (ICC is 0.87 and 0.82).Conclusions Hyaline imaging technology of three-dimensional pelvic floor sonography could be used to observe paravaginal support structure in women.The normal paravaginal support structure is typically showed as bilateral symmetrical tenting-like structure,which is on the same level as the center of ureter.It provides normal anatomic radiological evidence and helps study defect of paravaginal support structure caused by pregnancy or delivery.

Misuse and abuse of veterinary antimicrobial agents have led to an alarming increase in bacterial resistance, clinical treatment failure, and drug residues. To address these problems, consistent and appropriate dosage regimens for veterinary antimicrobial agents are needed. Pharmacokinetics/Pharmacodynamics (PK/PD) models have been widely used to establish rational dosage regimens for veterinary antimicrobial agents that can achieve effective prevention and treatment of bacterial diseases and avoid the development of bacterial resistance. This review introduces building methods for PK/PD models and describes current PK/PD research progress toward rational dosage regimens for veterinary antimicrobial agents. Finally, the challenges and prospects of PK/PD models in the design of dosage regimens for veterinary antimicrobial agents are reviewed. This review will help to increase awareness of PK/PD modeling among veterinarians and hopefully promote its development and future use.
Anti-Infective Agents ; Bacterial Infections ; Drug Residues ; Humans ; Treatment Failure ; Veterinarians

Objective:To investigate the relationship between social support and depression of only-child-lost (OCL) people,and the mediation role of self-efficacy in this relationship.Methods:By stratified cluster sampling,214 OCL people were enrolled,with 80 males and 134 females,ages from 49 to 83 years old.They were assessed by General Self-Efficacy Scale,Social Support Rating Scale,and Self-rating Depression Scale.Results:Univariate analysis showed that there were significant differences in age groups (t=2.85,P＜0.05),with or without spouse (t=5.62,P＜0.05),family location (t=3.95,P＜0.05),per capita monthly income (F=3.48,P＜0.05) among the social support scores.There was significant difference between the per capita monthly income and self-efficacy scores in QCL people (F=5.46,P＜0.05).Correlation analysis showed self-efficacy and social support were positively correlated (r=0.26,P＜0.01).Self-efficacy (r=-0.59,P＜0.01) and social support (r=-0.59,P＜0.01) negatively correlated with depression in OCL people.Self-efficacy partially mediated the relationship between social support and depression.Conclusion:The person who is ＜60 years old,with spouse and the high per capita monthly income,and lives the rural area,would have high social support levels among QCL people.The person who has high per capita monthly income would have high self-efficacy.Self-efficacy is one of the direct prediction for depression,and plays an indirect role between social support and depression.Intervention of depression among OCL people could be applied to change their cognition,and to enhance their self-efficacy.