ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4％.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P＜0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)％to the latest follow-up(11.30±3.27)％,and there was statistically significant different.The complication rate was 31.3％(45/144),and the reoperation rate was 9.72％(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14％(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.

OBJECTIVE To establish the quality standards of medicinal materials in light of related methods in the general principles of part four of Chinese Pharmacopoeia(2020 Edition), and to conduct systematic research on the Tibetan medicine "Yajima"(Chrysosplenium axillare). METHODS The powder characteristics of medicinal materials were described by microscopic identification method. Silica gel GF254 thin-layer plate was employed to establish a TLC identification method with 5-O-demethylapulein and oxyayanin A as reference substances. Loss on drying, total ash, acid-insoluble ash and ethanol-soluble extractives of 10 batches of Chrysosplenium axillare were determined according to the general principles of part four of Chinese Pharmacopoeia(2020 Edition). HPLC was used to establish the characteristic chromatogram of Chrysosplenium axillare, and the content determination method was established with chrysosplenoside I(CI) and chrysosplenoside A(CA) as the quality control index components of Chrysosplenium axillare. RESULTS The water content, total ash, acid-insoluble ash, ethanol-soluble extractive and the content of CI and CA of all samples varied in the ranges of 9.17%−12.52%, 14.11%−16.74%, 1.50%−4.72%, 32.77%−40.30%, 0.30%−0.99% and 0.28%−0.88%, respectively. CONCLUSION The identification and content determination methods of Yajima(Chrysosplenium axillare) are established for the first time. The methods are easy to operate and exclusive, which is of great significance to accurately evaluate the internal quality of medicinal materials and ensure the quality of drug used.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Sodium Hydroxide ; Acrylic Resins ; Escherichia coli ; Nanoparticles

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.
Pregnancy ; Female ; Humans ; Young Adult ; Adult ; Retrospective Studies ; Altitude ; China/epidemiology* ; Heart Defects, Congenital/diagnostic imaging* ; Heart Septal Defects, Ventricular ; Echocardiography ; Fetal Heart/diagnostic imaging*