Objective To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

OBJECTIVES: To identify 1-(4-fluorophenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-α-PVP) analog 1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-3-Methyl-α-PVP) hydrochloride without reference substance. METHODS: The direct-injection electron ionization-mass spectrometry (EI-MS), GC-MS, electrospray ionization-high resolution mass spectrometry (ESI-HRMS), ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS/MS), nuclear magnetic resonance (NMR), ion chromatography and Fourier transform infrared spectroscopy (FTIR) were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS. RESULTS: By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of ¹H-NMR and ¹³C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in ¹H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion (content 11.14%-11.16%), with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride. CONCLUSIONS A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.
Benzene ; Gas Chromatography-Mass Spectrometry/methods* ; Spectrometry, Mass, Electrospray Ionization ; Chromatography, High Pressure Liquid/methods*

In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R2=0.9981-0.9999),precision(interday precision of 1.6％-19.0％and intraday precision of 1.4％-19.8％)and accuracy(83.4％-115.7％).Moreover,the recovery assessments in tissues(82.5％-107.3％)and in cells(98.1％-118.9％)with GSH-13C2,15N,and Cys-15N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE-150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Critical Illness ; Cross-Sectional Studies ; Echocardiography ; Humans ; Intensive Care Units ; Lung/diagnostic imaging* ; Retrospective Studies

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.
Alkaloids ; Coptis ; Drugs, Chinese Herbal ; Humans ; Molecular Docking Simulation ; Structure-Activity Relationship ; Taste

Objective: To investigate the distribution pattern of late gadolinium enhancement (LGE) in left ventricular free wall of patients with dilated cardiomyopathy (DCM). Methods: A total of 130 consecutive DCM patients who were hospitalized in our hospital, underwent both CMR and CTA examinations and met the inclusion and exclusion criteria including negative results of coronary angiography or coronary CTA, were retrospective included in this study. The LGE pattern, extent and distribution in left ventricular free wall were analyzed. Results: Left ventricular free wall LGE was detected in 56 out of 130 DCM patients. LGE was observed in both septal and free wall in 53 out of 56 patients with LGE (94.6%). Prevalence of NYHA classification Ⅲ/Ⅳ, intraventricular block, paroxysmal ventricular tachycardia, and secondary mitral insufficiency was significantly higher, while left ventricular ejection fraction was significantly lower, left ventricular end-diastolic/systolic volume, left ventricular end-diastolic/systolic volume index and left ventricular end-diastolic diameters values were larger in patients with LGE than without LGE (all P<0.05). In terms LGE pattern among these 56 patients, percent of involved myocardial segments in patients with subepicardial LGE (n=19) was significantly higher than patients with intermural LGE (n=30), patients with transmural LGE (n=21), and patients with subendocardial LGE (n=9)(60.8%(127/209) vs. 32.4%(107/330), 32.5%(75/231), 26.3%(26/99), respectively, all P < 0.01). Transmural LGE was most likely to involve the left ventricular inferior lateral basal (18/21) and mid (13/21) segment, followed by anterior lateral basal (15/21) and mid (11/21) segments and inferior mid segment (9/21). Subepicardial LGE was more likely to occur in the inferior lateral basal (13/19) and mid (16/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, anterior lateral basal (13/19) and mid (15/19) segment, lateral apical (13/19), anterior and inferior mid segment (12/19 and 10/19), and apical segment (15/19 and 10/19). Intermural LGE mostly involved the anterior and inferior basal (19/30, 16/30) and mid (18/30 and 14/30) segment. There were 33 cases of single LGE pattern and 23 cases of multiple LGE pattern. Percent of involved myocardial segments was significantly higher in multiple LGE group than single LGE group (60.9% (154/253) vs. 49.9%(181/363), P = 0.007). Of 130 patients, 23 received heart transplantation, of which 6 patients had septal LGE alone and 17 patients had septal and free wall LGE. The rate of heart transplantation in the latter group was higher (32.1% (17/53)vs. 13.6%(6/44), P=0.034). Conclusions: There are several LGE distribution patterns in left ventricular wall among DCM patients.
Cardiomyopathy, Dilated/diagnostic imaging* ; Contrast Media ; Gadolinium ; Humans ; Magnetic Resonance Imaging, Cine ; Predictive Value of Tests ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

The aim of this study was to clarify the main components of the green leaves of Callicarpa nudiflora,and to compare the difference of main components between the green leaves,yellow leaves,branches and seeds. In this study,ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) coupled with the UNIFI scientific information system was adopted. And the identification of the main chemical components of C. nudiflora was combined with reference materials,literatures and online database. In addition,the difference of main components was analyzed by Progenesis QI,principal component analysis(PCA) and orthogonal partial least squares discriminant(OPLS-DA). A total of 57 compounds were identified in green leaves,including phenylpropanoids,flavonoids and iridoids. Among them,the relative content of phenylethanoid glycosides was highest. Furthermore,the PCA analysis showed that there are significant differences in main components of the branches and other parts of C. nudiflora. Combined with OPLS-DA analysis,nudifloside,parvifloroside B and β-hydroxysamioside were selected as the characteristic components for distinguish the leaves and branches of C. nudiflora. Our study provided a scientific basis for the collection and identification of C. nudiflora.
Callicarpa ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Flavonoids ; Tandem Mass Spectrometry

This article discussed Professor LI Li-yun's treatment experience in infertility caused by uterine factors from etiology, pathogenesis, treatment and prescription. Professor LI believes that a wide variety of pathogenic factors can lead to infertility caused by uterine factors, including cold, heat, deficiency and excess. According to this, the pathogenic factors should be distinguished and treatment should be conducted based on syndrome differentiation. Medical cases were studied to further explore Professor LI's clinical thoughts.