The odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees was analyzed and the relationship between the odor variation and the mildewing degree was explored. A fast discriminant model was established according to the response intensity of electronic nose. The α-FOX3000 electronic nose was applied to analyze the odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees and the radar map was used to analyze the main contributors among the volatile organic compounds. The feature data were processed and analyzed by partial least squares discriminant analysis(PLS-DA), K-nearest neighbor(KNN), sequential minimal optimization(SMO), random forest(RF) and naive Bayes(NB), respectively. According to the radar map of the electronic nose, the response values of three sensors, namely T70/2, T30/1, and P10/2, increased with the mildewing, indicating that the Pollygonati Rhizoma produced alkanes and aromatic compounds after the mildewing. According to PLS-DA model, Pollygonati Rhizoma samples of three mildewing degrees could be well distinguished in three areas. Afterwards, the variable importance analysis of the sensors was carried out and then five sensors that contributed a lot to the classification were screened out: T70/2, T30/1, PA/2, P10/1 and P40/1. The classification accuracy of all the four models(KNN, SMO, RF, and NB) was above 90%, and KNN was most accurate(accuracy: 97.2%). Different volatile organic compounds were produced after the mildewing of Pollygonati Rhizoma, and they could be detected by electronic nose, which laid a foundation for the establishment of a rapid discrimination model for mildewed Pollygonati Rhizoma. This paper shed lights on further research on change pattern and quick detection of volatile organic compounds in moldy Chinese herbal medicines.
Electronic Nose ; Odorants/analysis* ; Volatile Organic Compounds/analysis* ; Bayes Theorem ; Drugs, Chinese Herbal/analysis* ; Discriminant Analysis

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.
Chromatography, High Pressure Liquid ; Epimedium ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Multivariate Analysis

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans ; Acupuncture Therapy ; Periosteum ; Analgesia ; Pain Management ; Consciousness ; Pain

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.
Tandem Mass Spectrometry/methods* ; Multivariate Analysis ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Amino Acids/analysis*

Objective To evaluate the efficacy,safety and cost-effectiveness of alirocumab for the treatment of hypercholesterolemia in a rapid health technology assessment(rHTA).Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data and health technology assessment(HTA)relative websites were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literatures on the alirocumab for the treatment of hypercholesterolemia from inception to August 14th,2022.Two reviewers independently screened the literature,extracted the data results and accessed the quality of included studies.Descriptive analysis and summary were then performed.Results A total of 38 documents were included,including 28 systematic reviews/Meta analyses,7 pharmacoeconomic studies and 3 HTA reports.This study showed that,compared with placebo or other lipid lowering therapy,alirocumab lowered the levels of LDL-C,Lp(a),TC,TG,Apo B,non-HDL-C,increased the levels of HDL-C and Apo A1,reduced the risk of major adverse cardiovascular events(MACE),all-cause mortality,cerebrovascular events,and unstable angina,but did not reduce cardiovascular death,myocardial infarction or coronary revascularization.Safety studies showed that,compared with placebo or other lipid lowering therapy,alirocumab did not increase the risk of other adverse reactions but associated with higher injection site reactions.Pharmacoeconomic studies showed that alirocumab was cost-effective in patients with three branch coronary artery disease and acute coronary syndrome with LDL-C≥2.59 mmol·L-1.Conclusion Alirocumab is effective and safe for the treatment of hypercholesterolemia,and cost-effective for the patients of coronary arteriosclerotic heart disease with multi-vessel disease or with high base-line level of LDL-C.

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To observe the effects of four prostaglandin E2 (PGE2) receptors (EP 1-4R) on the activation of inflammasomes and cell damage in human retinal microvascular endothelial cells (hRMEC) in a high glucose environment. Methods:The hRMEC were divided into normal group and high glucose group, and they were cultured in Dulbecco modified Eagle medium containing 5.5 and 30.0 mmol/L glucose, respectively. Flow cytometry was used to observe the apoptosis rate of the high glucose group and the normal group; enzyme chain immunosorbent assay (ELISA) was used to detect the level of PGE2 in the culture supernatant of hRMEC cells. Western blot was used to detect the protein expression of cyclooxyganese (COX2) and EP 1-4R in hRMEC. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of EP 1-4R mRNA in hRMEC. After 72 h of culture, the cells in the high glucose group were divided into control group, PGE2 group, EP 1-4R agonist group, PGE2+EP 1-4R inhibitor group, and dimethylsulfoxide group. According to the group, each group was given the corresponding agonist or inhibitor to continue the culture for 24 h. QRT-PCR was used to detect the expression of nucleotide-binding oligomerization structure-like receptor protein (NLRP3) and pro-interleukin (IL)-1β mRNA in each group of cells. ELISA was used to detect the content of IL-1β and lactic dehydrogenase (LDH) in the cell culture supernatant. Western blot was used to detect the expression of cleaved Caspase-1 in each group of cells. At the same time, hRMEC in a high glucose environment was given IL-1β stimulation for 24 h, and the activity of LDH in the supernatant of the cell culture medium was detected. Results:The apoptotic rate, COX2 protein expression, and PGE2 protein content in hRMEC in the high glucose group were significantly higher than those in the normal group, and they were time-dependent. Compared with the normal group, the expression levels of EP 1R, EP 2R, EP 4R protein and mRNA in hRMEC in the high glucose group were higher than those in the normal group ( P<0.05). Compared with the control group, PGE2 group ( t=4.627, P<0.01), EP 1-4R agonist group ( t=3.889, 3.583, 2.445, 3.216; P<0.05) hRMEC NLRP3 mRNA expression level was significantly increased; the expression level of pro-IL-1β mRNA increased, however the difference was not statistically significant (PGE2 group: t=1.807, P>0.05; EP 1-4R agonist group: t=1.807, 1.477, 0.302, 1.926, P>0.05). Compared with the PGE2 group, the expression of NLRP3 mRNA in hRMEC in the PGE2+EP 2R inhibitor group was significantly reduced ( t=2.812, P<0.05); the expression of pro-IL-1β mRNA in hRMEC in the PGE2+EP 3R inhibitor group was significantly increased ( t=4.113, P<0.01). The protein content of IL-1β in the cell culture supernatant of the PGE2 group, EP 1R agonist group and EP 2R agonist group was significantly higher than that of the control group ( t=5.155, 4.136, 4.817; P<0.01). Compared with PGE2 group, the protein content of IL-1β in the cell culture supernatant of the PGE2+EP 2R inhibitor group and the PGE2+EP 4R inhibitor group were significantly lower than that of the PGE2 group ( t=1.964, 4.765; P<0.05). The expression of cleaved Caspase-1 in hRMEC in the PGE2 group and EP 2R agonist group was significantly higher than that in the control group ( t=5.332, 4.889; P<0.05). The expression of cleaved Caspase-1 in hRMEC in the PGE2+EP 2R inhibitor group was significantly lower than that of the PGE2 group ( t=6.699, P<0.01). The LDH activity in the cell culture supernatant of the PGE2 group and the EP 2R agonist group was significantly higher than that of the control group ( t=4.908, 4.225; P<0.05). The activity of LDH in the cell culture supernatant of the PGE2+EP 2R inhibitor group was significantly lower than that of the PGE2 group ( t=5.301, P<0.01). Compared with the control group, the LDH activity in the culture supernatant of hRMEC cells in the high glucose environment was significantly increased ( t=3.499, P<0.05). Conclusions:The four receptors of PGE2 can activate NLRP3 and its effector molecules to varying degrees. EP 2R mainly mediates hRMEC damage under high glucose environment.

Objective:To investigate clinicians' compliance with the 2018 Surviving Sepsis Campaign (SSC) update "1-hour sepsis Bundle therapy" (1-hour Bundle) when treating patients with Sepsis 3 in the intensive care unit (ICU), and to analyze its impact on patient outcomes.Methods:A multicenter, prospective observational cohort study was conducted. A total of 153 ICU patients in Ziyang First People's Hospital, Ziyang People's Hospital and Yanjiang District People's Hospital who were diagnosed of sepsis by the definition and diagnostic criteria of Sepsis 3 from January 2019 to December 2020 were selected. Among them, 95 patients who had completed 1-hour Bundle were divided into the Bundle compliance group. 58 patients who did not complete the Bundle within 1 hours were classified as the Bundle non-compliance group. The distribution of pathogenic bacteria and infected sites, 1-hour Bundle compliance and 28-day survival in the 3 hospitals were analyzed. Univariate analysis was used to analyze the risk factors affecting the prognostic between the two groups of sepsis patients. Cox regression model was used to draw a 28-day survival curve to evaluate the survival of the patients in the two groups.Results:Among 153 sepsis patients in 3 hospitals, the detection rate of pathogenic bacteria was 61.44% (94/153), and Gram-negative bacteria accounted for 79.79% (75/94). The top 3 infection sites were respiratory system, gastrointestinal tract and urinary system, accounted for 32.0%, 28.1% and 18.3%, respectively. In the 3 hospitals, 62.09% (95/153) of patients fully implemented the 1-hour Bundle. The poorly implemented indicators in the 1-hour Bundle were 1-hour blood microbial culture [77.78% (119/153)] and 1-hour antimicrobial application [79.74% (122/153)]. There was no significant difference in the baseline indicators between Bundle compliance and non-compliance groups. Univariate analysis showed that the main prognostic indicators: 28-day survival rate in the Bundle compliance group was significantly higher than that in the Bundle non-compliance group [80.00% (76/95) vs. 62.06% (36/58), χ2= 6.447, P = 0.014]. Secondary evaluation indicators: mean arterial pressure (MAP) at 6 hours and 24 hours in the Bundle compliance group were significantly higher than those in the Bundle non-compliance group [mmHg (1 mmHg = 0.133 kPa): 78.22±11.25 vs. 69.86±14.04, 79.78±11.45 vs. 75.35±12.90]. However, the median length of in hospital stay in the Bundle compliance group was significantly longer than that in the Bundle non-compliance group [days: 13 (17) vs. 6 (11)], with statistically significant differences (all P < 0.05). Bivariate Logistic regression analysis showed that 6 hours and 24 hours MAP were risk factors affecting the prognosis of patients with sepsis [odds ratio ( OR), 95% confidence interval (95% CI): 1.064 (0.994-1.102), 1.032 (1.003-1.063), both P < 0.05]. Conclusions:The 1-hour Bundle compliance rate of ICU patients with sepsis in 3 hospitals of Ziyang City was 62.09%, and the compliance is still to be improved, especially for the 2 aspects of empirical antimicrobial use and microbial culture retention before antimicrobial use. The 28-day survival rate in the Bundle compliance group was significantly higher than that in the Bundle non-compliance group, suggesting that the 1-hour Bundle regimen can improve the prognosis of patients with sepsis.