Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Removal of iatrogenic orbital foreign bodies with a 3D model

Facial foreign body (FB) is common after trauma, but iatrogenic orbital FB is a rare and unexpected complication of facial FB removal surgery. We present the case of a 43-year-old man with a glass FB in his nose. During the operation, this FB broke into two pieces, and the larger one pierced into the left orbit, close to the eyeball. A three-dimensional (3D) model was made that accurately recreated the shape and position of the FB in the orbit, according to which the FB was removed. 3D-printing technology is a great tool when dealing with complex facial FB.

A investigation of pathogenic Yersinia enterocolitica infection in children with diarrhea under 5 years of age in western Yunnan / 中国热带医学

@#Abstract: Objective To investigate the prevalence and pathogenic characteristics of Yersinia enterocolitica infection in children with diarrhea under 5 years of age in western Yunnan, and to provide a basis for the prevention and treatment of infectious diarrhea in children. Methods Feces were collected from under five-year-old children with diarrhea in the First Affiliated Hospital of Dali University from 2020 to 2021. Clinical information of the cases was also collected. Yersinia enterocolitica was isolated from the samples after cold enrichment on selective culture plates, and the pathogenic characteristics of Yersinia enterocolitica were analyzed by biological type and serotype and virulence gene detection. Results A total of 397 feces were collected. Seven strains of Yersinia enterocolitica were isolated in three samples, and the prevalence of Yersinia enterocolitica infection was 0.76% (3/397). Among the three positive samples, two Yersinia frederiksenii or Yersinia intermedia were isolated in specimen No. 212 , and five Yersinia enterocolitica were detected in specimens No. 24 and 226. Two Yersinia enterocolitica isolated from one sample were biological type 1A, and the virulence gene test results were ail-/ystA-/ ystB+ /yadA-/virF-, which were non-pathogenic Yersinia enterocolitica. Three Yersinia enterocolitica isolated from the other sample were biological type 3, serotype O∶3 (rfbc+), and virulence gene detection results were ail+/ystA+/ystB-/yadA+ /virF+, which were pathogenic Yersinia enterocolitica. While pathogenic Yersinia enterocolitica was detected from feces of children with diarrhea at 11 months of age with a infection rate of 0.50%(2/397). Conclusion Sporadic infection of pathogenic Yersinia enterocolitica was found in under five-year-old children in western Yunnan Province. It is necessary to strengthen the monitoring and research of Yersinia enterocolitica.

Expert consensus on late stage of critical care management / 中华内科杂志

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

Effects of screen exposure on language skills in children / 中华儿科杂志

Objective: To investigate the association between screen exposure and language skills in children aged 2-5 years. Methods: There were 299 children aged 2-5 years, recruited by convenience sampling from those who visited the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics for routine physical examination from November 2020 to November 2021. Their development status were evaluated by the children neuropsychological and behavioral scale (revision 2016). A self-designed questionnaire for parents was conducted to collect demographic and socioeconomic information and screen exposure characteristics (time and quality). One-way ANOVA and independent sample t test were applied to compare the differences in language development quotient of children with different screen exposure time and quality. Multiple linear regression was used to analyze the correlation between screen exposure time and quality with language developmental quotient. Multivariate Logistic regression was used to analyze the risk of language underdevelopment in children with different screen exposure time and quality. Results: Among 299 children, 184 (61.5%) were boys and 115 (38.5%) were girls, with the age of (3.9±1.1) years. The number of children with daily screen time <60, 60-120 and>120 min was 163 children (54.5%), 86 children (28.8%) and 50 children (16.7%), respectively, with the language development quotients of 94±13, 90±13, 84±14, respectively, demonstrating a statistically significant difference (F=8.92, P<0.001). Logistic regression analysis revealed that screen exposure time of 60-120 and >120 min per day were both risk factors for children's language developmental quotients (OR=2.28, 95%CI 1.00-5.17, P=0.043; OR=3.96, 95%CI 1.86-9.17, P<0.001), and co-viewing and exposure to educational programs were both protective factors for children's language developmental quotients (OR=0.48, 95%CI 0.25-0.91, P=0.024, OR=0.36, 95%CI 0.19-0.70, P=0.003). Conclusions: Excessive exposure screen time and inappropriate screen exposure habits are associated with children's poorer language development. Screen exposure time should be limited and screen use should be rational to promote children's language skills.

Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study / 中华预防医学杂志

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

Prediction of global potential growth areas for Panax ginseng based on GMPGIS system and MaxEnt model / 中国中药杂志

The suitable habitat for the endangered and valuable medicinal herb Panax ginseng is gradually decreasing. It is crucial to investigate its suitable growing areas in China for global protection and sustainable utilization of P. ginseng. In this study, 371 distribution points of P. ginseng were collected, and 21 environmental factors were used as ecological indicators. The geographic information system for global medicinal plants(GMPGIS) system, MaxEnt model, and Thiessen polygon method were used to analyze the potential suitable areas for P. ginseng globally. The results showed that the key environmental variables affecting P. ginseng were precipitation in the hottest quarter(Bio18) and the coefficient of temperature seasonality(Bio4). The suitable habitats for P. ginseng were mostly located in the "One Belt, One Road" countries such as China, Japan, South Korea, North Korea, and Russia. The highly suitable habitats were mainly distributed along mountain ranges in southeastern Shandong, southern Shanxi and Shaanxi, northern Jiangsu, and northwestern Henan of China. Data analysis indicated that the current P. ginseng planting sites were all in high suitability zones, and the Thiessen polygon results showed that the geographic locations of P. ginseng production companies were unbalanced and urgently needed optimization. This study provides data support for P. ginseng planting site selection, scientific introduction, production layout, and long-term development planning.

A new bibenzyl derivative from stems of Dendrobium officinale / 中国中药杂志

Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 μmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 μmol·L~(-1), indicating that it boasted hypoglycemic activity.

Mechanism of Modified Danggui Shaoyao San in treatment of chronic atrophic gastritis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Antimalarial and neuroprotective ent-abietane diterpenoids from the aerial parts of Phlogacanthus curviflorus / 中国天然药物

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC50 values of 12.97-65.01 μmol·L-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H2O2 and MPP+.

Research progress of anti-acute marrow leukemia drugs by targeting FLT3 / 药学学报

Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.

Efficacy differences between electroacupuncture and moxibustion for neurogenic bladder after spinal cord injury: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between electroacupuncture(EA) and moxibustion for neurogenic bladder (NB) after spinal cord injury (SCI).@*METHODS@#One hundred and twenty patients with NB after SCI were randomly divided into an EA group, a moxibustion group, and an intermittent catheterization group, with 40 patients in each group. The patients in the intermittent catheterization group were treated with routine treatment and intermittent catheterization, while the patients in the EA group and the moxibustion group were treated with additional treatments of EA (discontinuous wave, with a frequency of 1.3-1.6 Hz, and intensity based on patient tolerance) and moxibustion, respectively. The acupoints used in both groups were Zhongji (CV 3) and Guanyuan (CV 4), bilateral Zusanli (ST 36), Yinlingquan (SP 9), and Baliao points. Each session lasted for 30 min, once daily, six times a week, for a total of six weeks.The maximum bladder capacity (MBC), residual urine vdume (RUV), detrusor pressure (Pdet) during the filling phase, bladder compliance (BC), maximum renal pelvis separation width of both kidneys, urine white blood cell count, TCM syndrome score, and World Health Organization quality of life assessment-BREF (WHOQOL-BREF) score were compared before and after treatment in the 3 groups. The number of patients in each group who achieved bladder functional balance was recorded, and the clinical efficacy was assessed after treatment.@*RESULTS@#After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were increased (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, urine white blood cell count, and TCM syndrome scores were decreased (P<0.05, P<0.01). In the intermittent catheterization group, MBC, RUV, maximum renal pelvis separation width of both kidneys, and urine white blood cell count were decreased (P<0.05), while BC and WHOQOL-BREF score were increased (P<0.05) after treatment. After treatment, the MBC, Pdet, BC, and WHOQOL-BREF scores in the EA group and the moxibustion group were higher than those in the intermittent catheterization group (P<0.05), while the RUV and TCM syndrome scores were lower than those in the intermittent catheterization group (P<0.05). Moreover, after treatment, the MBC and Pdet in the moxibustion group were higher than those in the EA group (P<0.05), while the RUV, maximum renal pelvis separation width of both kidneys, and TCM syndrome score in the EA group were lower than those in the moxibustion group (P<0.05). The number of patients who achieved bladder functional balance after treatment in the EA group and the moxibustion group was higher than that in the intermittent catheterization group (P<0.05). The cured and effective rate was 85.0% (34/40) in the EA group and 82.5% (33/40) in the moxibustion group, which were both higher than 65.0% (26/40) in the intermittent catheterization group (P<0.05), there was no significant difference between the EA group and the moxibustion group (P>0.05).@*CONCLUSION@#EA and moxibustion could effectively improve the functional state of bladder in patients with NB after SCI. EA is more effective in reducing residual urine volume and excessive activity of the urethral sphincter, and relieving TCM syndromes, while moxibustion is more effective in increasing the pressure of the detrusor during the filling period and establishing the detrusor reflex.

Characterization of potential bitterness critical quality attributes in Xiaoer Ganmao Oral Liquid based on UHPLC-LTQ-Orbitrap MSn / 药学学报

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

Research on dynamic on-line monitoring method of moisture attribute in three honey-processed Chinese herbal slice based on in-situ general model / 药学学报

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

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.

Identification of taste critical quality attribute and formulation optimization of Xiaoer Qingrening Granules based on electronic tongue and human senses / 药学学报

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

Scarf osteotomy combined with soft tissue balance release for severe hallux valgus / 中国骨伤

OBJECTIVE@#To explore clinical effect of Scarf osteotomy combined with soft tissue balance in treating severe hallux valgus.@*METHODS@#Totally 38 patients(50 feet) with severe hallux valux who underwent Scarf osteotomy combined with soft tissue balance surgery from June 2019 to June 2021 were retrospectively analyzed, aged from 29 to 64 years old with an average of(54.7±6.8) years old; 26 feet on the left side and 24 feet on the right side;the courses of disease ranged from 5 to 23 years with an average of (12.4±3.9) years. Hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were compared before and after operation, and postoperative complications was observed. American orthopedic foot ankle society(AOFAS) score before operation and final follow-up was used to evaluate recovery of forefoot function, and visual analogue scale (VAS) was used to evaluate pain relief.@*RESULTS@#Thirty-eight patients (50 feet) were followed up from 15 to 23 months with an average of (18.3±3.2) months. Preoperative HVA, IMA and DMAA were (44.61±3.92)°, (18.74±2.51)°, (12.85±2.11)°, and improved to (13.45±2.13)°, (7.83±1.36)°, (7.03±1.39)°at final follow-up, which had statistical differneces(P<0.05). No delayed union or nonunion of osteotomy end, fracture or loosening of internal fixation, hallux varus occurred. VAS and AOFAS score improved from (6.81±2.14), (43.6±8.4)points before operation to (1.97±0.78), (87.6±5.2) points at final follow-up, which had statistical difference(P<0.01). According to AOFAS at final follow-up, 20 feet got excellent result, 28 feet good and 2 feet moderate.@*CONCLUSION@#Scarf osteotomy combined with soft tissue balance release for severe hallux valgus has good stability and corrective effect, but learning curve and postoperative complications should be paid attention.

Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer / 한국유방암학회지

Purpose@#Neoadjuvant chemotherapy (NAC) is widely used to treat breast cancer (BC). The prediction and evaluation of chemotherapy responses remains a significant challenge. @*Methods@#MicroRNAs (miRNAs) play a crucial role in cancer drug resistance. We used a miRNA microarray and identified that miR-638 is downregulated in chemoresistant cases.However, the exact role of miR-638 and the underlying mechanisms of chemoresistance remain unclear. Using real-time quantitative reverse transcription polymerase chain reaction, we found significant downregulation of miR-638 in chemoresistant patients compared with chemosensitive patients. To explore the function of miR-638, we overexpressed and inhibited miR-638 expression in MDA-MB-231 and MCF-7 cells by transfecting them with miR-638 mimics and miR-638 inhibitor, respectively. Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. A minimal patient-derived xenograft (MiniPDX™) model was established to evaluate the chemosensitivity to different drugs. @*Results@#The results showed that cell proliferation decreased and cell apoptosis increased in cells transfected with the miR-638 mimic, and cell proliferation and apoptosis were reversed with transfection of miR-638 inhibitor compared with the control group. Among patients who received 5-fluorouracil (5-FU), miR-638 expression levels were lower in the chemoresistant group than in the chemosensitive group. The MiniPDX™ model showed that MDA-MB-231 cells overexpressing miR-638 were more susceptible to 5-FU treatment in vivo. @*Conclusion@#We provided evidence of acquired resistance to 5-FU caused by miR-638 deficiency. Alterations in miR-638 may be used with 5-FU chemotherapy during NAC for BC.

Evaluation on the efficacy of moxifloxacin hydrochloride based on physiological pharmacokinetic models / 药学学报

This study is to establish and validation in vivo models of moxifloxacin based on the theory of physiologically based pharmacokinetics (PBPK), and then to predict the distribution of moxifloxacin in human venous return and organ such as lung, spleen and so on. The efficacy of moxifloxacin and its pharmaceutical preparations were quantified by comparing the pharmacokinetic parameters with the minimum inhibitory concentration of related pathogenic bacterium. The results showed that the anti-infection efficacy of pharmaceutical moxifloxacin preparation in the corresponding organs was basically the same. The PBPK model of moxifloxacin preparations can be more accurately described the pharmacokinetic of anti-infective drugs in human, it is suitable for the efficacy evaluation of anti-infective drugs and provides a strong basis for the corresponding scientific research and scientific supervision.