ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Premature ovarian insufficiency(POI) is a manifestation of ovarian aging, with a global incidence of 3.5%. If not addressed in time, POI can rapidly develop into premature ovarian failure(POF). The incidence of POI is mainly related to genetic factors, iatrogenic factors, autoimmunity, aging, infection, psychological factors, and other influences. POI not only causes menstrual disorders, amenorrhea, infertility, and dyspareunia but also tends to present with symptoms such as mood swings, insomnia, hot flashes, fatigue, as well as osteoporosis, coronary heart disease, diabetes, and other conditions, resulting in long-term psychological and physical health concerns for affected women. From traditional Chinese medicine(TCM)'s perspective, POI is primarily attributed to kidney Yin deficiency, with the main pathogenesis rooted in kidney deficiency, which affects the heart, liver, and spleen. It manifests in different syndrome types, including kidney deficiency with liver Qi stagnation, kidney deficiency with blood stasis, and spleen-kidney Yang deficiency. TCM employs a holistic view, utilizing multi-component TCM, multi-site acupuncture, and multi-target and multi-pathway interventions to treat POI. It offers unique advantages such as strong personalization, high safety, and good efficacy. In this paper, the animal and clinical research literature on the prevention and treatment of POI in the past 10 years was systematically summarized and reviewed. It is found that TCM mainly treats POI and alleviates POI-caused issues such as menstrual disorders, infertility, and emotional instability by regulating the neuroendocrine system(hypothalamic-pituitary-ovarian axis, HPOA) and related signaling pathways, improving ovarian function and antioxidant capacity, enhancing immune function, maintaining mitochondrial energy metabolism, inhibiting ferroptosis, and controlling endoplasmic reticulum stress.
Humans ; Primary Ovarian Insufficiency/physiopathology* ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Medicine, Chinese Traditional

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Abstract Gurrently, healthy behaviors are the cornerstone of both physical and mental wellbeing,and more researches are focusing on improving behaviors to alleviate depression among children and adolescents. Based on the concept of 24 h movement behaviors proposed in recent years, the study examines the relationship among physical activity, sedentary behavior, sleep and depressive symptoms in children and adolescents. The research suggests that physical activity could effectively alleviate depression among children and adolescents, and its effectiveness is influenced by factors including type, intensity, duration and frequency of physical activity. Excessive sedentary behavior may increase depressive symptoms, and the impacts of different types, durations, and frequencies of sedentary behavior on depressive symptoms among children and adolescents vary. In addition to its direct impact on depression, sleep could also serve as a mediator among physical activity, sedentary behavior and depression, and there is also a crowdingout effect of time between physical activity and sedentary behavior. Future research should focus on the mechanisms and pathways underlying how 24 h movement behaviors affecting depression among children and adolescents, in order to provide more accurate solutions for the prevention and treatment of depression.

OBJECTIVE: Current clinical evidence on the effects of home blood pressure telemonitoring (HBPT) on improving blood pressure control comes entirely from developed countries. Thus, we performed this randomized controlled trial to evaluate whether HBPT plus support (patient education and clinician remote hypertension management) improves blood pressure control more than usual care (UC) in the Chinese population. METHODS: This single-center, randomized controlled study was conducted in Beijing, China. Patients aged 30-75 years were eligible for enrolment if they had blood pressure [systolic (SBP) ≥ 140 mmHg and/or diastolic (DBP) ≥ 90 mmHg; or SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg with diabetes]. We recruited 190 patients randomized to either the HBPT or the UC groups for 12 weeks. The primary endpoints were blood pressure reduction and the proportion of patients achieving the target blood pressure. RESULTS: Totally, 172 patients completed the study, the HBPT plus support group ( n = 84), and the UC group ( n = 88). Patients in the plus support group showed a greater reduction in mean ambulatory blood pressure than those in the UC group. The plus support group had a significantly higher proportion of patients who achieved the target blood pressure and maintained a dipper blood pressure pattern at the 12th week of follow-up. Additionally, the patients in the plus support group showed lower blood pressure variability and higher drug adherence than those in the UC group. CONCLUSION HBPT plus additional support results in greater blood pressure reduction, better blood pressure control, a higher proportion of dipper blood pressure patterns, lower blood pressure variability, and higher drug adherence than UC. The development of telemedicine may be the cornerstone of hypertension management in primary care.
Humans ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Hypertension/therapy* ; Telemedicine/methods* ; Hypotension

Animals ; Bleomycin ; Epithelial-Mesenchymal Transition ; Lung ; Male ; Pulmonary Fibrosis/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Simvastatin/pharmacology*

Objective:To explore the effect of the care and nursing practice plan based on the timing theory in primary caregivers of infants with infantile spasms.Methods:From July 2019 to June 2020, 80 infants with infantile spasm and 80 primary caregivers in the Department of Neurology of Hunan Children's Hospital were selected as the research object. All infants with infantile spasms were numbered according to the time of admission. The odd-numbered infants were admitted to the First Department of Neurology as the observation group, and the even-numbered children were admitted to the Second Department of Neurology as the control group, with 40 infants and 40 primary caregivers in each group. The control group carried out conventional treatment and nursing, and the observation group implemented a care and nursing practice plan based on the timing theory on the basis of the control group. Before and after the intervention, the Caring Ability Inventory (CAI) , Family Caregiver Task Inventory (FCTI) , Caregiver Burden Inventory (CBI) , and Gesell Developmental Schedules (GDS) were used to evaluate the caring ability, caregiving ability, care load of the primary caregivers of the two groups of infants, and the cognition function of the two groups of infants.Results:After the intervention, the total CAI scores of the primary caregivers in the observation group were higher than those before intervention and those in the control group after the intervention, and the total scores of FCTI and CBI were lower than those before intervention and those in the control group after the intervention, and the differences were statistically significant ( P<0.05) . After the intervention, the developmental quotient (DQ) values of the five energy areas of GDS in the observation group were higher than those before the intervention, and the DQ values of the three energy areas of gross motor, fine motor, and language were higher than those of the control group after the intervention, and the differences were statistically significant ( P<0.05) . Conclusions:The care and nursing practice plan based on the timing theory can improve the caring ability and caregiving ability of the main caregivers of children with infantile spasms, reduce the care load, and improve the cognitive function of the children.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVE: To compare the clinical outcomes of microfracture and autogenous osteochondral mosaic transplantation in the treatment of knee joint cartilage injury. METHODS: A retrospective analysis of 71 patients with articular cartilage defects on the femoral condyles who were by autogenous osteochondral mosaic transplantation or microfracture from February 2011 to February 2016, and these patients were followed up for at least 2 years. According to the sugical procedures, the patients were divided into two groups. In the microfracture group, there were 33 patients, 20 males and 13 females, with a mean age of(28.1±4.2) years old; in the mosaicplasty group, there were 38 patients, 26 males and 12 females, with a mean age of(27.8±3.5) years old. The Lysholm knee score, Hospital for Special Surgery (HSS) knee score and the Ahlbäck classification grade were recorded to evaluate the clinical efficacy. Complications were also recorded. RESULTS: The mean Lysholm scores of the microfracture group and the mosaicplasty group improved from 62.9±6.8 and 60.3±7.5 preoperatively to 77.0±5.4 and 85.8±5.6 post-operatively, respectively(<0.05). Mean HSS scores of the microfracture group and the mosaicplasty group improved from 81.5±7.6 and 79.6±8.6 preoperatively to 88.0±4.7 and 91.9±4.7 post-operatively, respectively(<0.05). The mean Lysholm score and HSS score were significantly higher in the mosaicplasty group than those in the microfracture group at the latest follow-up. One patient in the mosaicplasty group suffered superficial wound infection. During the follow-up, no knee osteoarthritis was observed in two groups. CONCLUSIONS Autogenous osteochondral mosaicplasty and microfracture are proved to be safe and effective procedures for knee articular cartilage defects. However, the mosaicplasty has better clinical outcome than the microfracture.
Adult ; Cartilage, Articular ; Female ; Follow-Up Studies ; Fractures, Stress ; Humans ; Knee Joint ; Male ; Retrospective Studies ; Transplantation, Autologous ; Treatment Outcome ; Young Adult