ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Objective:To analyze the blood-transition prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor.Methods:Ultra-high performance liquid chromatographyquadrupole/electrostatic field orbital trap high resolution mass spectrometry (UHPLC-Q Exactive Focus MS/MS) technique was used to compare the chromatogram differences of Fengliaoxing Fengshi Dieda medicinal liquor extract, blank serum and drug-containing serum. According to the retention time, relative molecular weight and the ratio with primary and secondary ion fragments provided by MS, the prototype components and metabolites of Fengliaoxing Fengshi Dieda medicinal liquor extract were analyzed in serum of rats after oral administration. The detection conditions were as follows: the mobile phase of methanol (A)-0.1% formic acid solution (B) for elution gradient (0-5 min, 5%A; 5-60 min, 5%-95%A; 60-65 min, 95%A), the flow rate of 0.3 ml/min, heated electrospray ionization, detection range of m/z 80-1 200, positive and negative ion scanning modes.Results:A total of 31 transitional components were detected in the serum, of which 9 were prototype components and 22 were metabolites. The 9 prototype components were identified as phenylacetaldehyde, baogongteng C/ erycibellin, p-coumaric acid, 5-Hydroxymethylfurfural, quinic acid, paeonol, 3-Hydroxybenzaldehyde, salicylic acid, and isourecumenol. The 22 metabolites mainly consist of 11 organic acid components, 3 indole components, 2 organic phenolic components, 2 alkaloid components, 1 nucleoside component, 1 amino acid component, 1 lactone component, and 1 sulfonic component. The metabolic pathways were mainly glucuronidation, sulfation and others, which by phase Ⅱ metabolism.Conclusion:Organic phenols and organic acids are the main components that enter the body of Fengliaoxing Fengshi Dieda Medicinal Liquor, while alkaloid compounds and organic acid components may be potential active ingredients for its pharmacological effects.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

【Objective】 To generate reference values for inspiratory muscle of preschool children in Nanjing, so as to provide a reference index for evaluating children′s lung function and exercise performance. 【Methods】 A total of 236 preschool children were selected from the main urban area of Nanjing by stratified cluster sampling.The inspiratory muscles were evaluated by breath link respiratory function evaluation system to obtain the maximum inspiratory pressure (MIP) and inspiratory peak flow rate.Pearson analysis was used to determine the correlation of MIP and inspiratory peak flow rate with gender, age, height and weight.Multiple linear stepwise regression analysis was used to obtain the formula of MIP and inspiratory peak flow rate. 【Results】 Differences in MIP and peak inspiratory flow rate were not significant between boys and girls (P>0.05), but were statistically significant among different age groups and showed an increasing trend with age (F=13.660, 33.581, P<0.001).MIP and peak inspiratory flow rate were positively correlated with children′s age, height and weight (P<0.001).The regression model, proved to be statistically significant(F=12.913、22.398, P<0.08), indicated that height was the best predictor of MIP and age was the best predictor of inspiratory peak flow rate. 【Conclusions】 This study is the first study on the predicted value of inspiratory muscle in preschool children in China.The predicted value formula can provide a reference for clinical inspiratory muscle evaluation.

Objective To explore the research hotspots and development trends of Ziziphi Spinosae Semen in the past 20 years,and to provide reference for related research.Methods Literatures on Ziziphi Spinosae Semen were searched from January 1,2000 to December 31,2022 in CNKI,Web of Science Core Collection Database.VOS viewer software was used to visually analyze the citation frequency,research institutions and keyword hotspots of English literatures.CiteSpace software was used to visually analyze research institutions,authors,emergence keywords and keyword overlap time of Chinese literatures,and Microsoft Excel 2021 software was used to analyze of annual publication trends and publication volume of Chinese and English literatures,and download frequency of Chinese literatures.Results A total of 4 872 Chinese and 128 English literatures were included,with an overall upward trend in the number of annual publications.The research institutions with the highest number of publications in Chinese and English were Shandong University of Traditional Chinese Medicine and Tianjin University of Commerce,and the authors with the highest number of publications were DU Chenhui and XIE Junbo,respectively.The most frequent keywords in Chinese literatures were"Ziziphi Spinosae Semen","composed"and"application of compound therapy",and in English literatures were"performance","oxidative stress".Conclusion From 2000 to 2022,the research hotspots of Ziziphi Spinosae Semen mainly focused on the chemical composition,pharmacological effects and clinical application analysis,compatibility research,formulation and preparation.Quality control and evaluation of Ziziphi Spinosae Semen,and the research on the mechanism of preventing and treating insomnia with Ziziphi Spinosae Semen may become future research directions.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Objective : To investigate the effect of micro/nano hierarchical structures on the adhesion and proliferation of MC3T3-E1 cells, evaluate the drug delivery potential of titanium surfaces, and provide a reference for the modification of selected areas of titanium surfaces to enhance drug delivery and slow drug release. Methods : Pure titanium samples (10 mm in diameter and 2.5 mm in thickness) were randomly divided into a polished group (T), anodized group (TO), and micro/nano hierarchical structure group (FTO) according to the surface treatment of the titanium. The T group was polished, the TO group was treated with anodic oxidation technology, and the FTO group was treated by femtosecond laser etching combined with anodic oxidation technology. The three surface morphologies were observed by scanning electron microscopy (SEM), the wettability of the surface was measured by the contact angle, and the surface chemical composition was analyzed by X-ray energy dispersive spectroscopy (EDS). The depth of the FTO structure and the surface roughness were measured by confocal laser scanning microscopy (CLSM). MC3T3-E1 cell adhesion proliferation and differentiation on the surface of each group of samples was assessed by immunofluorescence staining, CCK-8, and semiquantitative analysis of Alizarin staining. A freeze-drying method was applied to load recombinant human bone morphogenetic protein-2 (rhBMP-2), and an enzyme-linked immunosorbent assay (ELISA) was used to assess the drug-loading potential of different surface structures. Results: SEM revealed that the surface of T group titanium plates showed uniform polishing marks in the same direction. The surface of the TO group was a nanoscale honeycomb-like titanium dioxide (TiO2) nanotube structure, and the FTO group formed a regular and ordered micro/nano layered structure. The contact angle of the FTO group was the smallest at 32° ± 1.7°. Its wettability was the best. The average depth of the first-level structure circular pores was 93.6 μm, and the roughness was 1.5-2 μm. The TO and FTO groups contained a high percentage of oxygen, suggesting TiO2 nanotube formation. The FTO group had the most significant surface cell proliferation (P<0.001) and the largest cell adhesion surface area (P<0.05). rhBMP-2 was slowly released for 14 d after loading in the FTO group and promoted extracellular matrix mineralization (P<0.001). Conclusion Titanium surface microprepared hierarchical structure has the effect of promoting MC3T3-E1 cell adhesion, proliferation, and osteogenic differentiation with drug loading potential, which is a new method of titanium surface treatment.

ObjectiveTo analyze the blood-transition constituents of Bergeniae Scopulosae Rhizoma extract based on the serum pharmacochemical method. MethodUltra-high performance liquid chromatography-quadrupole/electrostatic field orbital trap high resolution mass spectrometry （UHPLC-Q Exactive Focus MS/MS） technique was used to compare the chromatogram differences of Bergeniae Scopulosae Rhizoma extract， blank serum and drug-containing serum， according to the retention time， relative molecular weight and the ratio with primary and secondary ion fragments provided by MS， the prototype components and metabolites of Bergeniae Scopulosae Rhizoma extract were analyzed in serum of rats after oral administration. The detection conditions were as follows：the mobile phase of methanol （A）-0.1% formic acid solution （B） for elution gradient （0-40 min， 5%-95%A； 40-45 min， 95%A）， the flow rate of 0.3 mL·min^-1， the injection volume of 1 µL， heated electrospray ionization， detection range of m/z 80-1 200， positive and negative ion scanning modes. ResultAfter oral administration， a total of 35 components were detected in the serum， of which 6 were prototype components and 29 were metabolites of prototype components. The 6 prototype components were identified as arbutin， mallonanoside A， bengenin， ardimerin， salicylic acid and ellagic acid. The 29 metabolites were mainly metabolites from compound containing structural units such as gallic acid， mallonanoside A， bengenin， catechin， and ellagic acid， and their metabolic pathways were mainly glucuronidation， sulfation， methylation and others， which by phase Ⅱ metabolism. ConclusionThe components absorbed into the blood and their metabolites may be the pharmacodynamic components of Bergeniae Scopulosae Rhizoma. Among them， mallonanoside A， bengenin and ellagic acid can not only enter the blood as prototype components， but also exert their efficacy through phase Ⅱ metabolism. Most of the other chemical components in Bergeniae Scopulosae Rhizoma may be transformed into simple structures such as gallic acid， bengenin and catechin by hydrolysis， and then further metabolized by phase Ⅱ.

Polyporus umbellatus， as a traditional Chinese medicine for promoting diuresis and clearing dampness， mainly contains steroids and polysaccharides. It is usually used to treat diseases of urinary system. In this paper， the research progress of the effective components， pharmacological mechanisms and clinical use of P. umbellatus in diuresis-promotion and dampness- clearance is reviewed. Steroids such as ergosterone， peroxyergosterone， ergosta-7，22-dien-3-one and P. umbellatus polysaccharide PPS1， PPS2， PPS3， GUMP-1-1 and GUMP-1-2 promote diuresis and eliminate dampness through diuresis， renal protection， anti- inflammatory， bacteriostatic and immunomodulatory effects. Traditional Chinese medicine compound preparations such as P. umbellatus powder， P. umbellatus decoction， and Wuling powder have significant effects in treating urinary tract infections， lithiasis， renal edema and lesions， which providing reference for the further development and application of P. umbellatus.

OBJECTIVE: To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC). METHODS: A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO₂), oxygen consumption (VO₂) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups. RESULTS: Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO₂ and SV were significantly increased [DO₂ (mL×min^-1×m^-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L^-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ² = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ² = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO₂ factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042]. CONCLUSIONS dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.
Adult ; Humans ; Prospective Studies ; Ventricular Pressure ; Sepsis/complications* ; Shock, Septic/drug therapy* ; Cardiomyopathies/etiology* ; Prognosis