This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

Objective: To investigate the epidemiology, clinical characteristics, on-site dust monitoring and individual protection of the patients with artificial stone-related silicosis. Methods: In March 2022, the literature on artificial stone-related silicosis published from January 1965 to February 2022 was searched in China Journal Full-text Database, Wanfang Database, VIP Database, EMbase and PubMed. Chinese and English search terms include "silica dust""silica dust""silicosis""artificial stone""pneumoconiosis", etc. References were included according to inclusion and exclusion criteria, and data were extracted. The epidemiological characteristics, natural course of disease, workplace dust concentration and individual protection level of patients with artificial stone-related silicosis were analyzed by systematic review. Results: A total of 30 literatures were included, including 7 cohort studies, 14 cross-sectional studies, 3 case-control studies and 6 case reports. A total of 1358 patients with artificial stone-related silicosis were diagnosed from 1997 to 2020, with an average age of 41.5 years old and an average dust exposure time of 11.3 years. Among them, 36.2% (282/778) had progressive mass fibrosis or accelerated progressive silicosis at first diagnosis. Chest imaging showed diffuse small nodule shadow, pulmonary fibrosis, and silico-alveolar proteinosis. Pulmonary function showed restricted or mixed ventilation disorder with or without decreased diffusion volume. The disease progressed rapidly, with progressive mass fibrosis, respiratory failure, and even death. Patients engaged in artificial quartz stone processing, with high concentration of silica including ultra-fine particles, most of which were dry operation, lack of on-site ventilation measures and no effective personal protection. Conclusion: The artificial stone processing workers suffer from artificial stone-related silicosis due to dry cutting, lack of on-site dust removal facilities and personal protective measures, and the disease progresses rapidly, leading to poor prognosis.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells. METHODS: After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway. RESULTS: RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients. CONCLUSION RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.
Carbolines ; Cell Line ; Child ; Ferroptosis ; Humans ; Leukemia, Myeloid, Acute ; Pharmaceutical Preparations

OBJECTIVE: To observe the effect of moxa-cone moxibustion at lung's back- METHODS: Sixty SPF-grade healthy male Balb/c mice were randomly divided into a normal group, a model group, an LY294002 group (LY group), an electroacupuncture (EA) group and a moxibustion group, 12 mice in each group. Asthma model was replicated by using ovalbumin (OVA) sensitization. Except the mice in the normal group, all the mice were intraperitoneally injected with sensitization solution (containing 15 μg of OVA and 30 mg of aluminum hydroxide) on the 1st day, 7th day and 14th day, 0.5 mL per mice; from the 15th day, 1% OVA solution was atomized for 20 min, once a day for 2 weeks; the mice in the normal group was treated with identical operations but with 0.9% sodium chloride solution. The mice in the LY group were treated with injection of LY294002 at tail vein on the 13th day, 14th day and 15th day. At the beginning of the 15th day, The mice in the EA group were treated with EA at "Feishu" (BL 13) and "Zhongfu" (LU 1) with disperse-dense wave, frequency of 2 Hz/20 Hz, intensity of 1 mA, 15 min each time, once a day for 2 weeks. The mice in the moxibustion group was treated with moxa-cone moxibustion at "Feishu" (BL 13) and "Zhongfu" (LU 1) from the 15th day, three moxa-cones per acupoint, once a day for 2 weeks. On the 16th day, 18th day and 22nd day, the incubation period of asthma was recorded. On the 29th day, all the samples were collected. The expressions of IL-17 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The pathological changes of lung tissue were observed by HE staining. The percentage of Th17, Treg and Th17/Treg ratio in spleen tissue were detected by flow cytometry method. RESULTS: Compared with the normal group, the incubation period of asthma in the model group was significantly shortened ( CONCLUSION The Th17/Treg is imbalanced in asthmatic body. The moxibustion at lung's back-
Animals ; Asthma/therapy* ; Lung ; Male ; Mice ; Moxibustion ; T-Lymphocytes, Regulatory ; Th17 Cells

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.
Cerebral Palsy ; Child ; Child, Hospitalized ; Child, Preschool ; Humans ; Infant ; Malnutrition ; Nutrition Assessment ; Nutritional Status ; Treatment Outcome

Adult ; China ; Cognitive Dysfunction ; genetics ; Electric Power Supplies ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Power Plants ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism ; Receptors, Serotonin ; genetics ; metabolism ; Young Adult

In order to explore the chloroplast genome characteristics of Sophora flavescens and the phylogenetic relationship of the genus, this study used high-throughput sequencing technology to sequence and functionally annotate the chloroplast genome of Sophora flavescens. The results showed that the full length 154 165 bp of Sophora flavescens chloroplast genome showed a typical four-stage structure. The chloroplast genome contains 123 genes, including 77 protein-coding genes, 38 tRNA genes and 8 rRNA genes. Sequence analysis revealed 104 SSR loci, most of which consisted of A and T. In addition, the chloroplast genome codon preference is weak, and the coding region is biased towards the use of A and T bases. A comparative analysis of two different regions of Sophora flavescens chloroplast genome revealed four differential genes. Based on the maximum likelihood method (ML) for phylogenetic analysis of Sophora flavescens and 16 other leguminous, it was found that the relationship between Sophora flavescens and the genus Sophora alopecuroides is the closest. This study provides an important theoretical basis for the genetic variation, breeding and phylogenetic analysis of Sophora flavescens, and has certain reference value.

OBJECTIVE: To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients. METHODS: Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed. RESULTS: A total of 376 strains were isolated, 76.9% was Gram-negative bacterial and 23.1% was Gram-positive bacteria. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were listed as the top three of Gram-negative bacteria. The susceptibility of Escherichia coli to the tigacycline, imipenem and meropenem was 100.0%, 98.2% and 98.1%, respectively. The susceptibility of Klebsiella pneumoniae to the tigacycline, imipenem and meropenem were 100.0%, 98.3% and 94.4%, respectively. The adjustment rate for initial use of carbopenems was 3.8%, while the adjustment rate for initial use of noncarbopenems was 74.3% in patients with main Gram-negative bacterial blood stream infection. The susceptibility of Gram-positive bacteria to glycopeptide antibiotics, linezolid and tigacycline was 100.0%. CONCLUSION Gram-negative bacteria is the majority type of bacteria in AL patients with bacteria blood stream infections. The susceptibility of Gram-negative bacteria to the carbapenems is high, and the treatment adjustment rate is obviously low. The glycopeptide, linezolid and tigacycline are effective for Gram-positive bacteria infections..
Bacteremia ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Humans ; Microbial Sensitivity Tests ; Retrospective Studies