The aim of this study was to investigate the effect of baicalein on a Drosophila model of hereditary Parkinson's disease caused by gene mutations and to preliminarily elucidate the mechanism of baicalein in delaying hereditary Parkinson's disease. In this paper, PTEN-induced putative kinase 1 (PINK1)-RNAi Parkinson's Drosophila were used as the model group and wild-type Drosophila w¹¹¹⁸ were used as the control group. Different doses of baicalein and Madopa were administered to the model group to observe their effects on the life span, motor ability, the abnormal rate of wings, dopamine content and dopaminergic neurons of PINK1-RNAi Parkinson's Drosophila and their effects on mitochondrial dysfunction including adenosine triphosphate (ATP), mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) content. The results showed that the effective administration doses of baicalein were 0.8 mg·mL^-1 for low concentration, 1.6 mg·mL^-1 for medium concentration and 3.2 mg·mL^-1 for high concentration, and the optimal administration dose of the positive drug Madopa was 0.1 μg·mL^-1. Baicalein and Madopa could significantly improve the life span, exercise ability and reduce the abnormal rate of wings of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; baicalein could improve the loss of dopaminergic neurons, and the effects of low dose and high dose were the best, but Madopa showed no significant effect; baicalein and Madopa had no significant effect on dopamine content (P > 0.05). Baicalein and Madopa could increase the ATP content of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; middle dose baicalein could significantly increase the mtDNA content of PINK1-RNAi male Drosophila (P < 0.05), but Madopa had no significant effect; baicalein and Madopa had no significant effect on ROS content (P > 0.05).

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.
Administration, Cutaneous ; Skin Absorption ; Chromatography, Liquid ; Oils, Volatile ; Viscosity

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.
Animals ; Rats ; Cell Proliferation ; Collagen Type I/metabolism* ; Fibrosis ; Hepatic Stellate Cells ; HMGB1 Protein/genetics* ; Liver Cirrhosis/pathology* ; MicroRNAs/metabolism*

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

OBJECTIVES: To explore the sleep status and risk factors for sleep problems in infants and young children in Jilin Province. METHODS: A total of 1 080 healthy infants and young children aged 0-3 years from eight prefecture-level cities and one autonomous prefecture in Jilin Province were selected as subjects. A self-designed questionnaire was used to collect the general information of the subjects, and the Brief Infant Sleep Questionnaire was used to understand the sleep status of the subjects. Multivariate logistic regression analysis was used to analyze the risk factors for sleep problems. RESULTS: The total detection rate of sleep problems in the infants and young children was 38.24% (413/1 080). The total sleep time in the 4-11 month, 12-24 month, and 25-36 month age groups was higher than the recommended total sleep time (P<0.05). Multivariate logistic regression analysis showed that full-term birth, higher educational level of the main caregiver, and higher daytime activity intensity were protective factors for sleep problems in the infants and young children (P<0.05), while lower frequency of vitamin D supplementation, frequent night feeding, and maternal snoring were risk factors for sleep problems (P<0.05). CONCLUSIONS The total sleep time of infants and young children over 4 months old in Jilin Province is higher than the recommended total sleep time, but the prevalence rate of sleep problems is higher. The occurrence of sleep problems is related to various factors. Strengthening follow-up on preterm infants, providing education on infant sleep knowledge to primary caregivers, and regularly supplementing with vitamin D can be beneficial in reducing sleep problems in infants and young children.
Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Cross-Sectional Studies ; Infant, Premature ; Risk Factors ; Sleep ; Sleep Wake Disorders/epidemiology*

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca²⁺ current. Using noise analysis of Ca²⁺ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca²⁺ channels along with Ca_V1.3 expression. All these changes could act synergistically to enhance the Ca²⁺ influx into IHCs. Inhibition of intracellular Ca²⁺ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.
Humans ; Frankincense/chemistry* ; Commiphora ; Resins, Plant/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24⁺) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.
Abdominal Cavity ; Acupuncture Points ; Acupuncture Therapy/methods* ; Humans ; Tic Disorders/therapy*

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals ; China ; Cysteine-Rich Protein 61/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod/adverse effects* ; Inflammation/drug therapy* ; Intercellular Adhesion Molecule-1/genetics* ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Psoriasis/pathology* ; RNA, Messenger/therapeutic use*

Aim To investigate the anti-tumor effect of celastrol(CEL)on colorectal cancer and the possible targets/mechanisms. Methods The cytotoxic activities of CEL were evaluated against A549, HCT-116, HepG2 by CCK-8 method. Western blotting was used to detect the expression level of STAT3 and its upstream and downstream proteins(JAK2, Survivin, MCL-1)in HCT-116 cells before and after CEL treatment Flow cytometry was applied to assess CEL's apoptosis and cell-cycle arrest effect in HCT-116 cells. SPR detection and molecular docking analysis were performed to further assess the binding ability between CEL and STAT3 protein. Lastly, human colorectal cancer organoid culture was constructed to verify the anti-tumor effect of CEL. Results CEL showed significant cytotoxicity to A549(IC50 = 2.37±0.02 μmol·L-1), HCT-116(IC50 = 1.40±0.21 μmol·L-1)and HepG2(IC50 = 2.52±0.02 μmol·L-1). Additionally, CEL could effectively decrease the level of p-STAT3 and the downstream gene expression of STAT3(Survivin and MCL-1)in a concentration-dependent manner; however, CEL did not affect the total level of STAT3 and upstream kinases JAK2. Moreover, CEL could induce apoptosis of HCT-116 cells concentration-dependently and arrest the cell cycle. According to the SPR analysis, CEL showed a strong binding affinity with the KD value(the equilibrium dissociation constant)of 60.38 μmol·L-1. Molecular docking analysis also suggested that CEL bound to the SH2 domain of STAT3. Lastly, CEL showed much better activity than the positive drug oxaliplatin(L-OHP)on all the colorectal cancer organoids. Conclusions CEL shows a significant anti-colorectal cancer effect, potentially caused by a direct target inhibiting STAT3, inducing apoptosis, and blocking the cell cycle.