OBJECTIVE To explore the construction of selection system for drug directory of the county-level medical community based on multi-criteria decision analysis， and provide decision-making basis for the selection of drug directory of medical community. METHODS Taking county-level medical community in Chongqing as an example，Delphi method and analytic hierarchy process were employed to construct the selection system for drug directory of the county-level medical community. Selected drugs were quantitatively scored based on the constructed index system， and the drug directory was selected according to the drug’s comprehensive score. The implementation effect of the directory was then evaluated through questionnaire surveys one year after the implementation of the directory. RESULTS The expert authority coefficients of the two rounds of consultation were＞ 0.8， with Kendall’s W values of 0.213 and 0.196， respectively （P＜0.001）. Finally， the selection system for drug directory of the medical community was determined to include five evaluation dimensions： safety， effectiveness， economy， accessibility， and innovation， along with eight evaluation indicators. In the drug directory selected according to the above method， the proportions of centrally procured drugs， medical insurance drugs， and essential drugs had all increased compared to before the selection； the comprehensive scores of chemical drugs ranged from 50.25 to 96.31 scores， and the proportion of drugs scoring between 70 and 100 scores had increased from 78.06% before selection to 85.82%. Among them， antiparasitic drugs had the highest comprehensive scores， while drugs for the digestive tract and metabolism were the most numerous. The evaluation scores of each indicator and the comprehensive scores of drugs in the drug directory after the selection process increased significantly than before selection （P＜ 0.05）. CONCLUSIONS The selection system for drug directory of the county-level medical community constructed in this study is scientific， objective and operable. This process facilitates the promotion of standardized and unified management of drugs in the medical community.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

The traditional commodity specifications of Chinese medicinal materials are mainly divided into different grades based on macroscopic characteristics. As the basis for high quality and good price, there is still a lack of systematic evaluation on whether they are consistent with the current standards and whether they can reflect the internal quality of medicinal material. Panax notoginseng is a commonly used, large consumption of Chinese medicinal material. At present, it is divided into 8 grades in the market based on "Tou" (the number of crude drug /500 g), but it is not related to the standard of total saponins of Panax notoginseng (the sum of three saponins) in Chinese Pharmacopoeia. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) coupled with mass spectrometry molecular network were used for the rapid identification of saponins of Panax notoginseng with different "Tou" and a total of 64 saponins were identified. Seventeen saponins related to "Tou" were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). The content of five saponins R₁, Rb₁, Rg₁, Rd, and Re in Panax notoginseng with different "Tou" was determined by high performance liquid chromatography (HPLC). The results of correlation analysis showed that Rd and R₁ with the largest VIP values among the differential saponins, which significantly negatively correlated with "Tou" (P < 0.05). Based on the determination results of 36 batches of samples, using Rd/Total Panax notoginseng saponins (TPNS) ratio ( > 0.08) as the index, Panax notoginseng can be divided into two grades: 20-60 "Tou" (superior) and 80-200 "Tou" (qualified). Based on the concept of "macroscopic characteristics and chemical profiling", this study integrates the non-targeted analysis and quantitative determination methods to provide a new strategy for quality evaluation of Panax notoginseng.

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

Objective To explore whether superovulation impairs the process of pregnancy establishment in mice by changing the intrauterine environment. Methods The implantation and pregnancy of superovulated and normal mice were compared. The superovulated mice were subjected to unilateral tubal ligation on day 0. 5 and blastocysts were transplanted to the other uterine horn on day 2. 5. The number of implantation sites of bilateral uterine horn was compared. The differences between preimplantation uteri of superovulated and normal pseudopregnancy mice were compared by tissue sections and high-throughput sequencing. Bioinformatics analysis was performed on the differentially expressed genes in two groups. Results Compared with the control group, the pregnancy rate of mice in the superovulation group decreased significantly. The number of implantation sites in the superovulation group was higher than the control. There was no significant difference in the pregnancy rate of the uterine horn between the control side and the transplanted side of the superovulated mice. The endometrium was thinned and the number of glands was reduced in superovulated pseudopregnancy mice. The gene expression patterns of preimplantation uterus in superovulation pseudopregnancy and normal pseudopregnancy mice were different. There were 1097 significantly differentially expressed genes, including 752 up-regulated genes and 345 down-regulated genes. Bioinformatics analysis showed that differentially expressed genes are mainly involved in biological processes, such as decidualization, response to progesterone, positive regulation of angiogenesis. They were mainly enriched in FoxO signaling pathway, cell cycle pathway and steroid biosynthesis pathway. Conclusion Superovulation impaired the process of establishing pregnancy and altered the gene expression patterns of biomarker of uterine receptivity in mice.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective To explore the clinical characteristics and prognostic factors of elderly patients with commu-nity-acquired bloodstream infection(CA-BSI),and provide basis for clinical treatment and prevention.Methods Medical records of elderly patients diagnosed with CA-BSI in a tertiary first-class hospital of Changsha from 2017 to 2021 were collected.Patients were divided into a survival group and a death group according to the prognosis after 30 days hospitalization.The differences in clinical data between two groups of patients were compared,and influen-cing factors for the prognosis in CA-BSI patients were analyzed.Results A total of 575 elderly CA-BSI patients were included in the analysis,with 535 cases in the survival group and 40 cases in the death group.Univariate ana-lysis results suggested that death of elderly CA-BSI patients was related to gender,age,history of hemodialysis,glucocorticoid usage,indwelling catheter,concomitant heart disease,albumin,creatinine,and sequential organ fai-lure assessment(SOFA)score(all P＜0.05).Multivariate logistic regression analysis results suggested that old age(OR=1.062,95％CI:1.016-1.109),high SOFA score(OR=1.161,95％CI:1.067-1.262),glucocorti-coid usage(OR=6.006,95％CI:2.441-14.774)were independent risk factors for the death of elderly CA-BSI patients,while normal albumin(OR=0.942,95％CI:0.891-0.995)was a protective factor.Conclusion Elderly CA-BSI patients have high risks of death.It is necessary to improve the immunity of patients as well as use antimi-crobial agents and glucocorticoids rationally,so as to reduce the risk of death in patients.

The pre-market approval and clinical application of innovative medical devices should be based on high-quality evidence, proving their reliability, safety and effectiveness. In 2016, the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) collaboration modified the original IDEAL framework and recommendation to the IDEAL-D methodological framework for the entire life cycle evaluation of innovative medical devices. The framework included five stages, namely the preclinical development stage, idea stage, exploration stage, assessment stage and long-term follow-up stage. This paper aims to interpret the study purpose, content and design at each step of the IDEAL-D framework based on IDEAL framework and recommendation (2019) to provide practical methodological guidance for the design and conduct of clinical research on innovative medical devices.

The UHPLC-LTQ-orbitrap-MS metabolomics technique was used to determine the effect of deapio-platycodin D (DPD) on endogenous metabolites in lung tissues of mice with ammonia-induced cough, and to identify the metabolic regulatory pathways of DPD in its antitussive and expectorant activities. This work was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235). Metabolites were identified by UHPLC-LTQ-orbitrap-MS method and the metabolic pathways related to differentially-expressed metabolites were analyzed by the MetaboAnalyst platform. DPD significantly prolonged (P < 0.05) cough latency, reduced the number of coughs, and significantly increased (P < 0.05) phenol red excretion in ammonia-induced cough mice. Twenty-five metabolites related to cough and 38 metabolites related to sputum excretion were identified by UHPLC-LTQ-orbitrap-MS. Changes in the metabolism of linoleic acid, arachidonic acid, glycerophospholipid, alanine, aspartic acid and glutamic acid, pentose and glucuronate interconversions, and lysine degradation were evident with DPD treatment of ammonia-induced cough mice. Changes in the metabolism of linoleic acid, taurine and hypotaurine, glycerophospholipid, purines and pyrimidines, arachidonic acid and the biosynthesis of unsaturated fatty acids after DPD treatment were related to phenol red excretion. Linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism are common regulatory pathways by which DPD appears to exert its antitussive and expectorant activity. These metabolic pathways are closely related to anti-inflammatory pathways, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and apoptosis. This study clarifies the antitussive and expectorant activity and mechanism of DPD.