ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg^-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.

Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E₂-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

Objective:To establish a method for determining the concentration of gatifloxacin in rabbit ocular tissue and compare the ocular pharmacokinetics of 0.3% gatifloxacin eye gel after a single and multiple topical instillations in rabbits.Methods:Ninety-four healthy New Zealand rabbits were selected.Ten rabbits were randomly selected without any treatment for blank tissue collection, and the remaining 84 rabbits were randomly divided into a single-dose group (36 rabbits) and a multiple-dose group (48 rabbits) equally between males and females using a random number table.The left eye was taken as the experimental eye.The single-dose group was given one drop of 0.3% gatifloxacin eye gel into the left eyes, and the rabbits were divided evenly into six subgroups.In each subgroup, tear specimens and blood specimens were collected at 0.5, 1, 3, 5, 7, 10 hours after gel application, then cardiac blood samples were taken, after which animals were sacrificed immediately to collect ocular tissue including aqueous humor, conjunctiva, cornea, sclera, iris-ciliary body, lens, vitreous body, retina, and choroid.The multiple-dose group was given 1 drop of gatifloxacin ophthalmic gel in the left eye three times a day.At 0.5 hour after the first administration days 4 and 6, and 0.5, 1, 3, 5, 7, and 10 hours after the first administration on day 7, the cardiac blood sampling and ocular tissue collection were performed.The methanol precipitation protein method was used to pretreat samples, and the concentration of gatifloxacin in rabbit plasma and eye tissue was measured and calculated by high-performance liquid chromatography-tandem mass spectrometry method to obtain pharmacokinetic-related parameters such as peak concentration (C max), peak time (T max), and area under curve (AUC).The mobile phase was a methanol-0.1% acetic acid aqueous solution (volume ratio=70∶30), and a positive ion multiple reaction detection mode was used.Ciprofloxacin was used as the internal standard, the selectivity, standard curve and lower limit of quantification, accuracy and precision, extraction recovery rate, matrix effect, and stability of the method were validated in accordance with the 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples in Chinese Pharmacopoeia ( 2020 edition).Combined with the minimum inhibitory concentration (MIC 90) of gatifloxacin on common ocular infectious bacteria, C max/MIC 90 and AUC/MIC 90 were calculated.The study protocol was reviewed and approved by the Animal Ethics Committee of Shenyang Xingqi Pharmaceutical Co., Ltd.(No.XQ-2016-011). Results:Gatifloxacin has a good linear relationship in various eye tissues and plasma.The between-run precision in corneal tissue is within the range of -1.5%-6.0%, and the daytime precision was not greater than 15%.The extraction recovery rate in corneal tissue ranged from 92.0% to 94.8%, and the precision of the matrix effect at low, medium, and high concentrations calculated by internal standard normalization was not greater than 3.3%.After a single topical instillation, gatifloxacin reached a high concentration in anterior and posterior segment ocular tissues and its distribution ranked in order from the highest to the lowest by AUC 0-t as follows, tears, cornea, conjunctiva, iris-ciliary body, sclera, aqueous humor, choroid, retina, lens and vitreous body, with the C max of 94.90 μg/g, 7.34 μg/g, 3.65 μg/g, 1.81 μg/g, 1.75 μg/g, 1.31 μg/ml, 0.86 μg/g, 0.53 μg/g, 0.13 μg/g and 0.07 μg/ml, respectively.T max was 1 hour in all ocular tissues except in the lens, choroid, and vitreous body fluid, where T max was 0.5 hour.There was no significant difference among the concentrations of gatifloxacin in ocular tissues at 0.5 hour on days 4, 6 and 7 after multiple dosing ( P>0.05), and the AUC 0-t in the cornea, conjunctiva, and sclera was approximately 2.04, 2.12, and 2.32 times that of the single dosing.The concentration of gatifloxacin released into the systemic circulation after single and multiple dosing was less than 25.00 ng/ml.For both Staphylococcus aureus and Staphylococcus epidermidis, pharmacokinetic/pharmacodynamics in the conjunctiva, cornea, sclera, iris-ciliary body, aqueous humor, and choroid were satisfied with C max/MIC 90≥10 and AUC/MIC 90≥30 after continuous administration of gatifloxacin ophthalmic gel. Conclusions:A rapid and sensitive method for measuring gatifloxacin concentration in ocular tissues is successfully constructed.Gatifloxacin ophthalmic gel administered three times a day for three days can achieve stable concentrations in ocular tissues, and the concentration of gatifloxacin in ocular tissues is increased compared with a single dose.Effective treatment of common bacterial infections of the conjunctiva, cornea, sclera, and iris-ciliary body can be achieved with topical application of gatifloxacin ophthalmic gel.

Objective: To investigate the oncologic and surgical safety of the fused fascia method for immediate breast reconstruction with implants. Methods: The clinical data of 343 patients with immediate breast reconstruction with implants in Tianjin Medical University Cancer Hospital from 2014-2017 were retrospectively analyzed to compare the 5-year local recurrence-free survival, 5-year disease-free survival and 5-year overall survival of patients with breast reconstruction by fusion fascia and other methods, and to analyze the complication incidences of implant removal between different implant groups. Results: Of the 343 patients with breast reconstruction, 95 were in the fused fascia group (fascia group) and 248 were in the non-fascia group (25 in the bovine pericardial patch group and 223 in the muscle flap group). At a median follow-up of 49 months, the differences in 5-year local recurrence-free survival (90.1% and 94.9%, respectively), 5-year disease-free survival (89.2% and 87.6%, respectively), and 5-year overall survival (95.2% and 95.1%, respectively) between patients in the fascial and non-fascial groups were not statistically significant (P>0.05). The complication incidence of implant removal was 24.0% (6/25) in the patch group and 2.1% (2/95) and 2.2% (5/223) in the fascia and muscle flap groups, respectively. Conclusion: Immediate breast reconstruction with fused fascial combined with implant is safe and feasible, less invasive than muscle flaps, more economical and with fewer complications than patches.
Humans ; Animals ; Cattle ; Female ; Mastectomy/methods* ; Retrospective Studies ; Breast Implants/adverse effects* ; Feasibility Studies ; Mammaplasty/methods* ; Breast Neoplasms/complications* ; Treatment Outcome ; Postoperative Complications/surgery*

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.
Plant Extracts/pharmacology* ; Asteraceae ; Triterpenes ; Sesquiterpenes/pharmacology* ; Anti-Inflammatory Agents ; Phytochemicals/pharmacology*

Objective:To explore the relationship between stigma, psychological resilience and quality of life in patients with stable schizophrenia.Methods:This study is a cross-sectional study. From January to December 2021, 305 patients with stable schizophrenia who were treated in the Outpatient Department of the Affiliated Brain Hospital of Nanjing Medical University were selected by convenient sampling. The survey was carried out by using the General Information Questionnaire, the World Health Organization Quality of Life-Brief Form (WHOQOL-BREF) , the Connor-Davison Resilience Scale (CD-RISC) , and the Perceived Devaluation Discrimination (PDD) . Pearson correlation analysis was used to analyze the relationship between quality of life, stigma and psychological resilience of schizophrenia patients. The structural equation model was established using AMOS 25.0 and the intermediary effect was verified. A total of 305 questionnaires were distributed and 286 valid questionnaires were recovered, with an effective recovery rate of 93.8% (286/305) .Results:Among 286 patients with stable schizophrenia, the scores of psychological resilience, stigma and quality of life were (56.49±14.28) , (29.62±5.70) and (63.15±11.67) respectively. There was a positive correlation between the psychological resilience and the quality of life ( r=0.461, P<0.01) , a negative correlation between the stigma and the quality of life ( r=-0.328, P<0.01) , and a negative correlation between the stigma and the psychological resilience ( r=-0.309, P<0.01) . The results of intermediary effect analysis showed that psychological resilience played a part of intermediary role between the stigma and the quality of life, and the indirect effect was statistically significant (β=- 0.167, P<0.001) , the intermediary effect accounted for 32.2% of the total effect. Conclusions:Psychological resilience is an intermediary variable between the stigma and the quality of life in patients with stable schizophrenia. Nurses should carry out intervention strategies based on the impact of psychological resilience path to reduce the patients' stigma and improve their quality of life.

Chinese medicine processing is a procedure to process medicinal materials under the guidance of traditional Chinese medicine(TCM) theories by using unique methods in China. The medicinal materials can only be used clinically after proper processing. With the development of the modernization of TCM, it is difficult to solve the problems in the inheritance, development, and internationalization of Chinese medicine processing. Metabonomics, a new omics technology developed at the end of the last century, is used to infer the physiological or pathological conditions of the organism with the methods such as NMR and LC-MS via investigating the changes in endogenous small molecule metabolic network after the organism is stimulated by external environment. Metabonomics coincides with the holistic view of TCM because it displays the characteristics of integrity, comprehensiveness, and dynamics, and it has been widely applied in the field of Chinese medicine processing in recent years. This study summarized the application of metabonomics in the processing mechanism and quality control of Chinese medicine processing and prospected the development of this technology in the field of Chinese medicine processing.
Chromatography, Liquid ; Drugs, Chinese Herbal ; Mass Spectrometry ; Medicine, Chinese Traditional ; Metabolomics/methods* ; Quality Control