Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Exosomes derived from Nr-CWS pretreated MSCs facilitate diabetic wound healing by promoting angiogenesis via the circIARS1/miR-4782-5p/VEGFA axis / 中国天然药物

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Advances in research methods for biosynthetic pathway analysis of active ingredients in traditional Chinese medicine / 中国中药杂志

The active ingredients in traditional Chinese medicine(TCM)are the foundation for the efficiency of TCM and the key to the formation of Dao-di herbs. It is of great significance to study the biosynthesis and regulation mechanisms of these active ingredients for analyzing the formation mechanism of Daodi herbs and providing components for the production of active ingredients in TCM by synthetic biology. With the advancements in omics technology, molecular biology, synthetic biology, artificial intelligence, etc., the analysis of biosynthetic pathways for active ingredients in TCM is rapidly progressing. New methods and technologies have promoted the analysis of the synthetic pathways of active ingredients in TCM and have also made this area a hot topic in molecular pharmacognosy. Many researchers have made significant progress in analyzing the biosynthetic pathways of active ingredients in TCM such as Panax ginseng, Salvia miltiorrhiza, Glycyrrhiza uralensis, and Tripterygium wilfordii. This paper systematically reviewed current research me-thods for analyzing the biosynthetic functional genes of active ingredients in TCM, elaborated the mining of gene elements based on multiomics technology and the verification of gene functions in plants in vitro and in vivo with candidate genes as objects. Additionally, the paper summarized new technologies and methods that have emerged in recent years, such as high-throughput screening, molecular probes, genome-wide association studies, cell-free systems, and computer simulation screening to provide a comprehensive reference for the analysis of the biosynthetic pathways of active ingredients in TCM.

One-year clinical observation of the effect of internal bleaching on pulpless discolored teeth / 华西口腔医学杂志

OBJECTIVES@#This study aimed to observe the color rebound and rebound rates of non-pulp discolored teeth within 1 year after routine internal bleaching to guide clinical practice and prompt prognosis.@*METHODS@#In this work, the efficacy of bleaching was observed in 20 patients. The color of discolored teeth was measured by using a computerized colorimeter before bleaching; immediately after bleaching; and at the 1st, 3rd, 6th, 9th, and 12th months after bleaching. The L*, a*, and b* values of the color of cervical, mesial, and incisal parts of the teeth were obtained, and the color change amounts ΔE*, ΔL*, Δa*, and Δb* were calculated. The overall rebound rate (P*) and the color rebound velocity (V*) were also analyzed over time.@*RESULTS@#In 20 patients following treatment, the average ΔE* of tooth color change was 14.99. After bleaching, the neck and middle of the teeth ΔE* and ΔL* decreased in the 1st, 3rd, 6th, 9th, and 12th months, and the differences were statistically significant. Meanwhile, from the 9th month after bleaching, the rebound speed was lower than that in the 1st month, and the difference was statistically significant. The incisal end of the tooth ΔE* and ΔL* decreased in the 6th, 9th, and 12th months after bleaching, and the differences were statistically significant. No significant difference was found in the rebound speed between time points. However, this rate settled after the 9th month, with an average color rebound rate of 30.11% in 20 patients.@*CONCLUSIONS@#The results indicated that internal bleaching could cause a noticeable color change on pulpless teeth. The color rebound after bleaching was mainly caused by lightness (L*), which gradually decreased with time, and it was slightly related to a* and b*. The color of the teeth after internal bleaching rebounded to a certain extent with time, but the color rebound speed became stable from the 9th month. Clinically, secondary internal bleaching can be considered at this time according to whether the colors of the affected tooth and the adjacent tooth are coordinated and depending on the patient's needs.

Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Progress in research into the wedge effect during cephalomedullary nailing for intertrochanteric fractures / 中华创伤骨科杂志

Surgical intervention is the first choice treatment for intertrochanteric fractures that are common in clinical practice. Cephalomedullary nailing with two parts inserted respectively into the femoral medullary cavity and femoral head has been the mainstream protocols for the elderly patients with intertrochanteric fracture, but insertion of the cephalomedullary nail may likely lead to the outward displacement of the femoral shaft and the inversion and rotation of the head and neck bone mass, namely the so-called wedge effect. However, few reports have dealt with how to prevent the wedge effect and reduce the complications it may cause such as coxa vara deformity. The present review expounds and analyzes the concept, biomechanical mechanism, influencing factors, measurements, and prevention methods of the wedge effect, hoping to help the surgeons who try to avoid the wedge effect in surgical treatment.

Clinical characteristics of severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections in children / 中华传染病杂志

Objective:To analyze the clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections in children, and to provide reference basis for the SARS-CoV-2 vaccination in children.Methods:A total of 97 children aged 3 to 14 years and diagnosed with coronavirus disease 2019 (COVID-19) admitted to Xi′an People′s Hospital (Xi′an Fourth Hospital) from December 27, 2021 to February 7, 2022 were included. According to the COVID-19 vaccination status, the enrolled children were divided into unvaccinated group, partially vaccinated group and fully vaccinated group, and the clinical data of the children in the three groups were collected and compared. Chi-square test, two independent sample t-test and Kruskal-Wallis H test were used for statistical analysis. Results:Totally 97 children including 49 males and 48 females were enrolled, with 87(89.7%) children of mild type, 10(10.3%) children of common type, and no severe or critical case. The proportions of unvaccinated, partially vaccinated and fully vaccinated preschool-aged children (3 to 6 years old) were 56.5%(13/23), 30.8%(12/39) and 17.1%(6/35), respectively, while those of school-aged children (7 to 14 years old) were 43.5%(10/23), 69.2%(27/39) and 82.9%(29/35), respectively. The vaccination proportion in preschool-aged children was significantly lower than that in school-age children ( χ2=9.94, P=0.007). The proportion of the children with fever in fully vaccinated group was 17.1%(6/35), which was lower than that in unvaccinated group (43.5%, 10/23), and the difference was statistically significant ( χ2=4.82, P=0.028). The cycle threshold (Ct) values of the open reading frame ( ORF)1 ab gene in the unvaccinated, partially vaccinated and fully vaccinated groups were 33.77(26.87, 36.58), 35.23 (33.45, 38.57) and 37.12 (34.91, 39.39), respectively, and there was a statistically significant difference among the groups ( H=7.76, P=0.021). The Ct values of the nucleocapsid protein ( N) gene in the three groups were 32.26(25.85, 36.18), 35.12(33.18, 37.96) and 37.26(34.27, 39.24), respectively, and the difference among the groups was statistically significant ( H=7.84, P=0.020). The Ct values of ORF1 ab gene and N gene in fully vaccinated group were higher than those in unvaccinated group, and the differences were statistically significant ( Z=-2.69, P=0.007 and Z=-2.39, P=0.017, respectively). The duration of viral shedding in fully vaccinated children was (9.9±4.1) d, which was shorter than that in unvaccinated children ((12.8±3.7) d), and the difference was statistically significant ( t=2.72, P=0.009). Conclusions:The majority of children with breakthrough infections with SARS-CoV-2 are mild. Vaccination may effectively shorten the duration of viral shedding. And fully vaccination is associated with mild clinical symptoms and lower serum viral load compared to unvaccinated children.

A latent class analysis of feeding practices among preschoolers’ parents and its correlations with parental depression status / 中华行为医学与脑科学杂志

Objective:To explore the latent classes of parental feeding behaviors in preschool children, and to examine the relationship between potential types of parental feeding behaviors and parental depression status.Methods:From May to July 2021, parents of preschoolers from eight kindergartens in Shanghai were recruited and investigated.A paper-based questionnaire consisting of the Chinese preschooler’s caregivers’ feeding behavior scale (CPCFBS) and the center for epidemiological studies depression scale (CESD-10) was employed.Finally, a total of 1 006 valid questionnaires were retrieved.Mplus 8.0 and SPSS 26.0 were used for statistical analysis.The latent class analysis was used to identify subgroups of parents based on their feeding practices.Multinomial Logistic regression was used to examine the relevant influencing factors.Results:The feeding behaviors of parental of preschool children could be divided into four potential categories: " high responsiveness and high non-responsiveness type" (24.55%), " low responsiveness and high non-responsiveness type" (27.44%), " high responsiveness and low non-responsiveness type" (28.33%) and " low responsiveness and low non-responsiveness type" (19.68%). The parents with depression status were less likely to be categorized as " high responsiveness and low non-responsiveness type" ( OR=0.386, 95% CI: 0.218-0.684). The parents with older children were more likely to be categorized as " low responsiveness and low non-responsiveness type" ( OR=1.318, 95% CI: 1.039-1.672). Conclusion:The feeding practices of parents of preschool children can be categorized into four latent classes.The parents with depression status are more likely to adopt non-responsive feeding practice than responsive feeding practice.Actively paying attention to and improving the depression status of parents may help the feeder to adopt scientific feeding behavior.

A case of liver failure caused by fatal amanita poisoning was successfully treated by open cholecystostomy drainage / 中华危重病急救医学

The fatality rate of liver failure caused by fatal amanita poisoning is high, and there are no effective antidote drugs in China. On July 30, 2020, the department of infectious diseases and liver diseases of the First People's Hospital of Yunnan Province admitted a 67-year-old female patient with liver failure caused by fatal amanita poisoning. The patient went to the emergency department for treatment due to abdominal pain, vomiting and diarrhea after eating 350-400 g of amanita mushroom for 2 days, accompanied by fatigue for 1 day. There was no abnormality in physical examination. Laboratory indexes: alanine aminotransferase (ALT) 4 798 U/L, aspartate aminotransferase (AST) 10 030 U/L, activated partial thromboplastin time (APTT) 57.5 s, prothrombin time (PT) 72.1 s, international normalized ratio (INR) 8.66, prothrombinactivity (PA) 10%. Based on the patient's medical history, clinical manifestations and laboratory data, the diagnosis was amanita peptide mushroom poisoning and acute liver failure. According to the mechanism of amanita toxin poisoning as enterohepatic circulation, endoscopic retrograde cholangiopancreatography and ultrasound-guided gallbladder puncture and drainage for drainage of bile to discharge toxins were performed to interrupt the enterohepatic circulation of toxins. However, both methods failed, so open cholecystostomy was performed. Because the patient's coagulation function was very poor, artificial hepatic plasma exchange was given to improve coagulation function before open cholecystostomy, and eventually bile was drained successfully. After a total of 19 days of comprehensive medical treatment, the patient was cured and discharged from the hospital, and no sequelae was found after 1 year of follow-up. For such patients, early identification of the disease is required, and blocking the enterohepatic circulation of toxins as soon as possible according to the characteristics and toxicological mechanism of toxins may be the key treatment for rescuing patients with liver failure poisoned by amanita toxin, and it is necessary to combine comprehensive treatments such as active fluid replacement and blood purification to further improve the survival rate.

Research progress of soluble growth stimulating gene 2 protein in cardiovascular disease / 中国基层医药

Growth stimulating gene 2 (ST2) protein is a member of the interleukin-1 receptor family. It is mainly divided into a soluble secreted form sST2 and a transmembrane form ST2L. sST2 is a decoy receptor that competitively binds to interleukin-33 to block the interleukin-33/ST2L signaling pathway, worsening myocardial hypertrophy, fibrosis, and ventricular dysfunction. Measuring sST2 is of important value for diagnosis and/or prognosis evaluation of cardiovascular diseases. This paper mainly reviews the research progress in the relationship between cardiovascular diseases such as heart failure, coronary heart disease, hypertension, atrial fibrillation, myocarditis, cardiomyopathy, acute aortic dissection, and pulmonary hypertension, and sST2.

Effects of different analgesic methods of hydromorphone on analgesic efficacy and sleep quality in patients with refractory cancer pain / 中国基层医药

Objective:To investigate the effects of different analgesic methods of hydromorphone on analgesic efficacy and sleep quality in patients with refractory cancer pain.Methods:Sixty patients with refractory cancer pain who received three-step analgesic treatment in Quzhou People's Hospital from August 2018 to December 2019 and acquired poor analgesic effects were included in this study. They were randomly assigned to undergo either an intravenous patient-controlled analgesia with hydromorphone (HV group, n = 30) or an intrathecal patient-controlled analgesia with hydromorphone (HI group, n = 30) for 10 consecutive days. The analgesic efficacy in each group was evaluated using the numerical rating scale (NRS) before and 2, 4, 24, 48 hours, and 10 days after administration. The frequency of breakthrough pain (BTP) at each time point was recorded. The sedation effect of medication was evaluated using the Ramsay score. The sleep quality of patients was evaluated using the Pittsburgh sleep quality index (PSQI). The activities of CD 3+, CD 4+, and CD 4+/CD 8+ lymphocyte subsets were measured by flow cytometry at different time points. The adverse reactions within 10 days after treatment were observed and recorded. Results:Before and at each time point after treatment, there were no significant differences in NRS score, the frequency of BTP, Ramsay score, and PSQI score between the two groups (NRS score: t = 0.45, 0.91, 0.52, 1.19, 0.97, 1.92, all P > 0.05; frequency of BTP: t = 0.34, 1.88, 0.86, 1.71, 1.22, 0.76, all P > 0.05; Ramsay score: t = 0.56, 0.46, 0.63, 0.22, 0.99, 0.14, all P > 0.05; PSQI: t = 0.86, 1.25, 1.46, 1.05, 0.57, 1.93, all P > 0.05). At each time point after treatment, the activities of CD 3+, CD 4+, and CD 4+/CD 8+ cells increased in each group, and the activities of CD 3+, CD 4+, and CD 4+/CD 8+ cells in the HI group were significantly higher than those in the HV group (CD 3+: t = 3.72, 3.12, 2.85, 3.13, 2.44, all P < 0.05; CD 4+: t = 3.62, 2.45, 3.31, 3.19, 2.70; all P > 0.05; CD 4+/CD 8+: t = 3.10, 2.74, 2.83, 3.24, 3.41, all P < 0.05). The total incidence of adverse reactions was slightly, but not significantly, lower in the HI group than the HV group [14.00% (7/30) vs. 26.00% (13/30), χ2 = 2.70, P = 0.100]. Conclusion:Compared with intravenous administration of hydromorphone, intrathecal administration of hydromorphone can better effectively relieve pain, decrease the frequency of BTP, improve sleep quality, has a good sedative effect, improve immune function, and has fewer adverse reactions.

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single- Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. @*Materials and Methods@#We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. @*Results@#Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. @*Conclusion@#Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology / 药学学报

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Monitoring results of plague vector fleas in Yulong ，Yunnan Province from 2019 to 2021 / 上海预防医学

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ2=15.851， P<0.01； χ2=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.

Influence of GLCCI1 gene rs37973 polymorphism on the efficacy of ICSs in the treatment of asthma-chronic obstructive pulmonary disease overlap / 中国药房

OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Multimodal imaging features of perifoveal exudative vascular anomalous complex / 中华眼底病杂志

Objective:To observe the multimodal imaging features and explore the treatment of parafoveal exudative vascular anomaly complex (PEVAC).Methods:A retrospective study. Six patients (6 eyes) with PEVAC diagnosed in Tianjin Eye Hospital were included in this study from July 2018 to December 2021. All patients were female with monocular disease. The age was (61.1±9.3) years. All patients showed a sudden painless decline in monocular vision with metamorphopsia. All patients underwent best corrected visual acuity (BCVA), color fundus photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and OCT angiography (OCTA). Indocyanine green angiography (ICGA) was performed in 4 eyes. In 6 eyes, 3 eyes were treated with intravitreal injection of anti-vascular endothelial growth factor drug; 5 eyes were treated with micropulse laser photocoagulation and/or local thermal laser photocoagulation; 1 eye was treated with photodynamic therapy. Five patients were followed up for (9.2±7.4) months, and 1 patient was lost. At follow-up, the same equipment and methods were used as at the initial diagnosis. The clinical manifestations, multimodal image features and treatment response were observed.Results:Baseline BCVA of affected eyes were ranged from 0.1 to 0.5. PEVAC was isolated in 6 eyes, and the fundus showed isolated hemangioma-like leision, accompanied by small bleeding and hard exudation. There were 2 isolated hemangiomatous lesions adjacent to each other in 2 eyes. In the early stage of FFA, punctate high fluorescence lesions near the macular fovea were seen, and the leakage was enhanced in the late stage. There was no leakage in the early stage of ICGA, or slight leakage with late scouring. OCT showed an oval lesion with high reflection wall and uneven low reflection. The central macular thickness (CMT) was (431±76) μm. OCTA showed blood flow signals in PEVAC, 2 eyes in the superficial capillary plexus (SCP), and it was also observed in the deep capillary plexus (DCP), but the intensity of blood flow signal was slightly weaker than that in the SCP. The blood flow signal was visible only in DCP in 2 eyes. SCP and DCP showed similar intensity of blood flow signals in 2 eyes. After treatment, the bleeding was absorbed basically in 4 eyes, the hard exudation partially subsided, the CMT decreased, the intercortical cystic cavity of the fovea nerve decreased, the hemangiomatous lesions narrowed, and BCVA increased. In 1 eye, the macular sac was reduced and partially absorbed by hard exudation, which was later relapsed due to blood pressure fluctuation.Conclusions:The majority of PEVAC patients had monocular onset. The fundus is characterized by solitary or structure with strong reflex walls, with or without retinal cysts, hard exudates, and subretinal fluid, and visible blood flow signals inside.

Interpretation of presynaptic dopaminergic PET imaging results / 中华核医学与分子影像杂志

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.