Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Shikonin induces hepatocellular carcinoma cell apoptosis by suppressing PKM2/PHD3/HIF-1α signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of shikonin-induced death of human hepatocellular carcinoma SMMC-7721 cells.@*METHODS@#Cultured SMMC-7721 cells and normal hepatocytes (L-02 cells) were treated with 4, 8, or 16 μmol/L shikonin, and the changes in cell viability was assessed using MTT assay. The levels of ATP and lactic acid in the cell cultures were detected using commercial kits. Co-immunoprecipitation and immunofluorescence staining were used to determine the relationship among pyruvate kinase M2 (PKM2), prolyl hydroxylase 3 (PHD3), and hypoxia-inducible factor-1α (HIF-1α). The expressions of PHD3, PKM2, HIF-1α, Bax, cleaved caspase-3, and Bcl-2 in SMMC-7721 cells were detected with Western blotting, and cell apoptosis was analyzed with annexin V-FITC/PI staining. The effects of RNA interference of PKM2 on PHD3 and HIF-1α expressions in SMMC-7721 cells were detected using Western blotting.@*RESULTS@#The IC50 of shikonin against SMMC-7721 and L-02 cells was 8.041 μmol/L and 31.75 μmol/L, respectively. Treatment with shikonin significantly inhibited the protein expressions of PKM2, HIF-1α and PHD3 and nuclear translocation of PKM2 and HIF-1α in SMMC-7721 cells. Coimmunoprecipitation and immunofluorescence staining confirmed that shikonin inhibited the formation of PKM2/PHD3/HIF-1α complex and significantly reduced the contents of lactic acid and ATP in SMMC-7721 cells (P < 0.05). The expressions of PHD3 and HIF-1α decreased significantly after PKM2 knockdown (P < 0.05). Shikonin treatment significantly increased the apoptosis rate, enhanced the expressions of Bax and cleaved caspase-3, and decreased Bcl-2 expression in SMMC-7721 cells (P < 0.05).@*CONCLUSIONS@#Shikonin induces apoptosis of SMMC-7721 cells possibly by inhibiting aerobic glycolysis through the PKM2/PHD3/HIF-1α signaling pathway to cause energy supply dysfunction in the cells.

Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Diagnosis and Treatment of Traditional Chinese Medicine for Encephalopathy Based on the Theory of “Identificating the Onset of Diseases” / 中医杂志

Brain diseases in traditional Chinese medicine were complex and difficult to diagnosis and treatment， and new diagnostic and therapeutic ideas are urgently needed. The onset of the disease was the result of the struggle between healthy qi and pathogenic qi. Common types of the onset of diseases included sudden onset， slow onset， latent onset， secondary onset， and recurrent onset， reflecting the strength of the healthy qi and pathogenic qi， the pathogenic qi that reduced diseases， the site of onset， and other informatin. “Identificating the onset of diseases” was simple and easy to operate， and helped to clarify the complex development of encephalopathy. When applying it， we should first identify urgency and importance， focus on the characteristics； grasp the tendency of diseases， and know the overall situation of the disease； compare similarities and differences horizontally； and carefully observe and dynamically understand the disease. “Identificating the onset of diseases” has the characteristics of comprehensiveness and prognosis， and can lay the foundation for pattern identification and treatment and “treating disease before its onset”.

Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice / 数字中医药（英文）

Objective@#To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). @*Methods@#A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. @*Results@#Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). @*Conclusion@#Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

PAFR/Stat3 axis maintains the symbiotic ecosystem between tumor and stroma to facilitate tumor malignancy

Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

Health and functional outcome of whole body vibration for children and adolescents with cerebral palsy: a systematic review using WHO-FICs / 中国康复理论与实践

ObjectiveTo construct a research framework for systematic review of health and functional outcomes of whole body vibration training in children and adolescents with cerebral palsy based on the theory and method of World Health Organization Family of International Health Classifications (WHO-FICs), and to systematically review the major health conditions and physical functions, intervention programs of whole body vibration training, and health and functional outcomes of vibration intervention in children and adolescents with cerebral palsy. MethodsBased on the WHO-FICs method, the PICO architecture of systematic reviews was constructed, and the databases of CNKI, Wanfang Data, PubMed, Web of Science, EBSCO, and Embase were searched to collect randomized controlled trials about the health and functional effects of whole body vibration training on children and adolescents with cerebral palsy from the establishment to September 30th, 2022, and a systematic review was conducted. ResultsEight articles, seven in English and one in Chinese, from five countries, were included, mainly from journals in clinical rehabilitation, neurorehabilitation, physical medicine and rehabilitation, etc., published mainly after 2010, involving 227 participants (three to 12.3 years old). The quality of the articles was evaluated using the Physical Therapy Evidence Database scale with a mean score of six. The ICD-11 codes included 08 diseases of the nervous system, 8D20 spastic cerebral palsy, 8D20.1 spastic bilateral cerebral palsy, 8D20.10 spastic quadriplegia cerebral palsy and 8D2Z unspecified cerebral palsy. The primary functioning of cerebral palsy was characterized as muscle spasticity, abnormal skeletal development, joint deformities and muscle weakness, decrease of selective motor control and gait abnormalities; for the activity and participation, the functioning included walking difficulties, decrease of mobility and weight loading, and low levels of physical activities. The main intervention was whole body vibration, in postures of lying, squatting or standing, mainly standing, in the mode of vertical vibration. The frequency was 5 to 30 Hz, and the amplitude was below 9 mm, three to five times a week for eight weeks to six months. The intervention settings include medical institutions, schools and families; mainly for therapeutics and recovery. The health and health-related outcomes were mainly involved s7 structures related to movement, b710 mobility of joint functions, b730 muscle power functions, b735 muscle tone functions, b760 control of voluntary movement functions, d410 changing basic body position, d415 maintaining a body position, d450 walking, d455 moving around, and d420 transferring oneself; such as improvements of neuromusculoskeletal and joint functions, muscle spasm, static balance, muscle strength, and control of movement, the control of body posture and walking, range of activities and self-care. ConclusionWhole body vibration training is effective on cerebral palsy, mainly in standing position, 5 to 30 Hz, and amplitude below 9 mm; three to five times a week for eight weeks to six months. The outcomes of whole body vibration training are mainly reflected in the improvement of body-motor functions, and activity and participation.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Efficacy analysis of transfusion of suspended RBCs and washed RBCs in patients with positive direct Coombs testing results / 中国输血杂志

【Objective】 To compare the efficacy and safety of transfusion of suspended RBCs and washed RBCs in patients with positive direct Coombs testing results. 【Methods】 A retrospective analysis was conducted on 98 patients with positive direct Coombs testing results as 2+ or less in the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2020. Among them, 31 patients, from January 2015 to December 2016, were transfused with washed RBCs and set as the control group; the other 67 patients, from January 2017 to December 2020, transfused with suspended RBCs, were enrolled as the experimental group. The changes of main laboratory indexes and the incidence of transfusion adverse reactions before and after transfusion of 2 U and 4 U RBCs were compared between the two groups to evaluate the efficacy and safety of transfusion. 【Results】 After 2 U and 4 U transfusion, Hb increased by 12±4.967 (g/L) and 23.78±12.736 (g/L) in the control group, while 12.85±7.109 (g/L) and 22.68±9.832 (g/L) in the experimental group, All transfusions of the two groups were effective, and no significant differences in Hb, TBIL, IBIL and LDH were noticed by groups (P>0.05). No significant difference in the incidence of adverse reactions to blood transfusion between the 2 groups was observed (P>0.05). 【Conclusion】 The transfusion of suspended RBCs is safe and effective in patients with positive direct Coombs testing results as 2+ or less, and the transfusion of washed RBCs was unnecessary.

A comparison of binocular and monocular surgery on the effect of eye-covering pretreatment on emergence delirium after general anesthesia in pre-school aged children / 中国实用护理杂志

Objective:To evaluate the effect of eye-covering pretreatment on acute delirium in ophthalmology preschool-age children who underwent binocular and monocular surgery by general anesthesia.Methods:The 300 preschool-age children who underwent general anesthesia of elective ophthalmic surgery in the Second Affiliated Hospital, Zhejiang University School of Medicine, from August 2019 to February 2021 were selected as the research object. They were divided into control group and blindfold group with 150 cases each by random number-table. Children in the control group received regular education on cartoon animation videos before surgery; children in the blindfold group received eye-covering pretreatment on the basis of cartoon animation videos(monocular surgery with monocular cover, binocular surgery with binocular cover). The Modified Yale Preoperative Anxiety Scale (m-YPAS) , the Nursing Delirium Screening Scale(NU-DESC), the incidence rate of delirium and the score of postoperative nursing difficulty were compared between two groups.Results:The 271 cases were completed in this study, including 129 cases(monocular surgery 66 cases, binocular surgery 63 cases) in the blindfold group and 142 cases (monocular surgery 73 cases, binocular surgery 69 cases) in the control group. The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery in the blindfold group , monocular surgery was (40.28 ± 15.02) points, 1.00 (0.00, 2.00) points, 27.3%(18/66), 1.00 (1.00, 2.00) points,and binocular surgery was (41.69 ± 16.35) points, 1.00 (0.00, 2.00), 39.7%(25/63), 1.00(1.00, 2.00); in the control group, monocular surgery was (46.28 ± 15.76) points, 2.00 (1.00, 3.00) points, 67.1% (49/73), 2.00 (1.00, 3.00) points, and binocular surgery was (47.77 ± 14.82) points, 3.00 (2.00, 4.00) points, 82.6% (57/69) and 2.00 (1.50, 3.00) points respectively. The difference between the two groups was statistically significant ( t= -2.29, -2.24, Z values were -5.74 - -2.95, χ2= 32.94, 25.78, all P<0.05). The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery patients in the blindfold group had no significantly statistical difference with that of binocular surgery patient (all P>0.05) . Conclusions:Monocular/ binocular eye-covering pretreatment can effectively decrease the preoperative m-YPAS score, the postoperative NU-DESC score, incidence rate of acute delirium and the postoperative nursing care difficulty in preschool-age children who underwent general anesthesia both monocular or binocular surgery. There was no difference in the application effect of monocular or binocular surgery.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Application of liver three-dimensional visualized reconstruction technique in hepatectomy for children with complicated hepatoblastoma / 临床肝胆病杂志

Objective To investigate the application of liver three-dimensional (3D) visualized reconstruction technique in hepatectomy for children with complicated hepatoblastoma. Methods A retrospective analysis was performed for the clinical data of 30 children with hepatoblastoma who underwent hepatectomy for radical resection in PLA Rocket Force Characteristic Medical Center from January 2018 to October 2020, and according to whether liver 3D visualization with IQQA-Liver system was performed before surgery, the children were divided into 3D reconstruction group with 15 children and control group with 15 children. The two groups were compared in terms of perioperative parameters, short-term prognosis, and follow-up conditions. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Fisher's exact test was used for comparison of categorical data between two groups. Results Compared with the control group, the 3D reconstruction group had a significantly higher mean age (55.7±10.2 years vs 28.2±2.7 years, P 0.05). The median follow-up after surgery was 9.5 months. In the 3D reconstruction group, 2 children experienced recurrence and were diagnosed at 10 and 12 months, respectively, after surgery, and they were treated with chemotherapy at the moment; in the control group, 4 children experienced recurrence, which was higher than that in the 3D reconstruction group ( P =0.651), and among these 4 children, 2 had recurrence at 7 months after surgery, received liver transplantation, and survived up to now, and the other 2 children died shortly after recurrence. Conclusion 3D visualized reconstruction technique helps to perform hepatectomy for children with complicated hepatoblastoma more safely and accurately, especially extended hepatectomy for patients with stage POST TEXT III/IV hepatoblastoma, thereby avoiding liver transplantation.

Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation / 中国药科大学学报

@#Remdesivir-loaded liposomes for inhalation were prepared and the in vitro properties were evaluated. Firstly, preparation methods of remdesivir-loaded liposomes were screened, and single-factor experiments were conducted to optimize the prescription and preparation process. Then the physical property, deposition ratio and aerodynamic particle size distribution of remdesivir-loaded liposomes suspension for inhalation were comprehensively evaluated. As a result, the optimal liposomes were prepared by the thin-film dispersion method with pH 6.5 phosphate-buffered saline as the hydration medium. In the prescription, the ratio of drug to DPPC was 1∶20; the cholesterol accounted for 10% of total lipids; and 20% DSPE-mPEG 2000 was added as stabilizer.4% trehalose was added as lyoprotectant when lyophilizing to obtain ideal appearance, good stability and a small particle size change after reconstitution. Remdesivir-loaded liposomes were spherical with smooth surface and uniform particle size distribution under transmission electron microscope. In vitro release tests showed no significant change for release curves of remdesivir-loaded liposomes suspension before and after nebulization. Deposition experiments indicated that the fine particles fraction of liposomes was 51.4%, and the mass median aerodynamic diameter was less than 5 μm measured by next generation impactor. To sum up, remdesivir-loaded liposomes for inhalation with high encapsulation efficiency and stability can achieve a suitable particle size distribution to effectively deposit in the lung after nebulization, which provides a new approach for the treatment of COVID-19.

Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma (ESCC)

@#Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

Recent progress of robots in stomatology / 华西口腔医学杂志

With the development of industrial robot technology, robotics has entered the medical field, and the research and development of new robots for many medical applications have become a significant research direction in global robotics. Robots are widely used in various aspects of dentistry, such as prosthodontics, orthodontics, implants, endodontics, and oral surgery. This article mainly introduces the application of robots in stomatology from the above five aspects.

Effects and Mechanism of Buyang Huanwu Decoction and the like on Oxygen Deprivation and Reoxygenation of Hippocampal Neurons in Vitro / 中国药学杂志

OBJECTIVE: To investigate the effects and mechanism of Buyang Huanwu Decoction and the like on primary cultured neonate hippocampal neurons induced by oxygen deprivation and reoxygenation. METHODS: The primary cultured hippocampal neurons cell model was established, oxygen sugar deprivation/reoxygenation (OGD/R) model was established in vitro. CCK-8 was used to determine the concentration of Buyang Huanwu Decoction and the like drug-containing serum to protect hippocampal neurons cell. The experimental groups were divided into control group, model group, Buyang Huanwu Decoction drug-containing serum group(10%), Naoxintong Capsule drug-containing serum group(10%), Yangyin Tongnao Granules drug-containing serum group(10%), Buyang Huanwu Decoction drug-containing serum+TAK-242 group(10%,1 μmol•L-1), Naoxintong Capsule drug-containing serum+TAK-242 group(10%,1 μmol•L-1), Yangyin Tongnao Granules drug-containing serum+TAK-242 group(10%,1 μmol•L-1). The morphology of hippocampal neuron was observed under inverted microscope. The expression of tumor necrosis factor-α(TNF-α) and interleukin 1(IL-1β) in the cell supernatant was detected by ELISA kit. The neuronal cell apoptosis was observed by Hoechst 33358 staining fluorescence microscope and the expression of TLR4/NF-κB signaling pathway proteins was detected by Western blot. RESULTS: The results showed that hgher purity neuronal cells can be obtained by primary culture. Compared with model group, Buyang Huanwu Decoction and the like all can reduce the release of TNF-α and IL-1β in hippocampal neurons, significantly reduced the number of apoptosis. At the same time, the three traditional Chinese medicine compounds all can inhibit the expression of TLR4 and NF-κB protein in TLR4/NF-κB signaling pathway, and protect the inflammatory response of oxygenated sugar deprivation and reoxygenated hippocampal neurons. The addition of TLR4-specific inhibitor TAK-242 blocked the conduction of this signaling pathway and reduced the protective effect of Buyang Huanwu Decoction and the like. CONCLUSION: Buyang Huanwu Decoction and the like have protective effects on OGD/R-induced inflammatory response in hippocampal neurons, its mechanism may be related to TLR4/NF-κB signaling pathway, and the anti-inflammatory protective effect of Naoxintong Capsule is relatively obvious.

Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies / 南方医科大学学报

OBJECTIVE@#To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis.@*METHODS@#We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed.@*RESULTS@#A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS).@*CONCLUSIONS@#Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.

Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies / 浙江大学学报·医学版

OBJECTIVE@#To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis.@*METHODS@#We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed.@*RESULTS@#A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS).@*CONCLUSIONS@#Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.

Selection and discussion of the best treatment strategy for different types of rotator cuff injury / 中国组织工程研究

BACKGROUND: At present, the treatment of rotator cuff injury is still an emphasis and hotspot in orthopedics clinical research. Although the therapies of rotator cuff injury are constantly innovating and improving, there is still a lack of unified standards and understanding, and each treatment has different strengths, weaknesses and indications. OBJECTIVE: To provide more ideas for orthopedic clinicians to treat rotator cuff injury by summarizing the indications of different therapies of rotator cuff injury. METHODS: A computer-based online research of PubMed, Embase, The Cochrane Library and ClinicalKey databases was performed for relevant articles published from 1990 to 2019 with the keywords of “rotator cuff tear, rotator cuff injury, therapeutic, treatment and therapies”. The unrepresentative and over-dated articles and studies that did not meet the inclusion criteria were excluded, and finally 77 eligible articles were included for analysis and summary. RESULTS AND CONCLUSION: (1) The treatments of rotator cuff injury can be divided into conservative treatments and surgical treatments, in which surgical treatments mainly include rotator cuff debridement, superior articular capsule reconstruction, reverse shoulder arthroplasty, and subacromial balloon spacer. In the choice of these treatments, different types of rotator cuff injury have different indications. (2) It is worth noting that massive rotator cuff injury is still a challenge in clinical treatment due to the high surgical failure rate and postoperative retear rate. However, with the rapid development of material science and tissue engineering, the new adjuvant therapy technologies have been gradually applied in clinical practice, and have become the focus in the field of rotator cuff injury.

A five-year follow-up analysis of efficacy and complications of 3 932 cases of fecal microbiota transplantation treatment / 中华消化杂志

Objective:To observe the long-term efficacy and complication rate of fecal microbiota transplantation (FMT) and the effects of different ways of transplantation and treatment courses on the efficacy of FMT.Methods:From April 2012 to April 2020, the data of 3 932 patients (804 cases of Nanjing General Hospital of Nanjing Military Command and 3 128 cases of Tenth People′s Hospital of Tongji University) who voluntarily received FMT treatment were prospectively collected. After the first course of transplantation, the follow-up rate and efficacy and complications in 5 years were observed at the 1st, 12th, 24th, 36th, 48th and 60th month. According to the different ways of the first transplantation, 3 932 patients were divided into nasointestinal tube group (2 604 cases), capsule group (873 cases), colonoscopy group (268 cases) and enema group (187 cases). One month after transplantation, the effective rate and complication were observed. At the same time, the 1 813 patients with FMT less than four courses were divided into 1 treatment course group (369 cases), 2 treatment courses group (568 cases), 3 treatment courses group (497 cases) and 4 treatment courses group (379 cases). The effective rates of patients in four groups with different treatment courses were observed 6 months after finishing the treatment. Chi square test was used for statistical analysis.Results:Among 3 932 patients, the follow-up rates at 1st, 12th, 24th, 36th, 48th and 60th month after the first course of FMT were 93.67%(3 683/3 932), 82.30%(2 307/2 803), 82.17%(1 825/2 221), 62.41%(978/1 567), 59.85%(559/934) and 60.84%(289/475), respectively. The total effective rates at 1st, 12th, 24th, 36th, 48th and 60th month were 67.23%(2 476/3 683), 64.20%(1 481/2 307), 59.29%(1 082/1 825), 59.71%(584/978), 55.81%(312/559) and 59.17%(171/289), respectively. During FMT period, the total incidence of different complications was 34.49%(1 356/3 932). During follow-up period, the total rate of complication was 4.22%(166/3 932). There were no serious adverse events such as gastrointestinal perforation, multi-drug resistant bacterial infection, organ failure and death. One month after FMT, the effective rates of nasojejunal tube group, capsule group, colonoscopy group, and enema group were 67.18%(1 668/2 483), 68.63%(549/800), 67.23%(158/235), 61.21%(101/165), respectively. There was no significant difference among the four groups ( P>0.05). The effective rates of patients with chronic constipation in nasal jejunal tube group, capsule group and colonoscopy group were all higher than that of enema group (67.82%, 1 043/1 538; 67.98%, 138/203 and 62.96%, 17/27 vs. 26.67%, 8/30), and the differences were statistically significant ( χ2=22.55, 19.07 and 7.60, all P<0.01). During the period of FMT, the total incidence of complications of nasojejunal tube group, capsule group, colonoscopy group and enema group were 35.22%(917/2 604), 30.24%(264/873), 42.54%(114/268) and 32.62%(61/187), respectively. The difference was statistically significant among four groups ( χ2 =18.84, P<0.01). Among nasojejunal tube group, capsule group, colonoscopy group and enema group, there were significant differences in the incidence of diarrhea (4.49%, 117/2 604; 4.58%, 40/873; 7.83%, 21/268 and 5.35%, 10/187, respectively), throat pain (5.30%, 138/2 604; 0.69%, 6/873; 2.99%, 8/268 and 1.07%, 2/187, respectively), gastrointestinal bleeding (0; 0; 1.87%, 5/268 and 0.53%, 1/187, respectively) and enterogenous infection (0; 0; 1.49%, 4/268 and 0.53%, 1/187, respectively) ( χ2 =8.24, 39.24, 63.13 and 49.68, all P<0.05). At the 6th month after treatment, the effective rates of 1 treatment course group, 2 treatment courses group, 3 treatment courses group and 4 treatment courses group were 63.94%(211/330), 61.93%(301/486), 65.75%(286/435) and 72.54%(251/346), respectively. There were statistically significant differences among groups with different treatment courses ( χ2 =10.70, P =0.01). The effective rate of the four treatment courses group was significantly higher than those of the one treatment course group, two treatment courses group and three treatment courses group, and the differences were statistically significant ( χ2=5.78, 10.18 and 4.14, all P<0.05). The effective rates of in chronic constipation and autism in 4 treatment courses group were significantly higher than those in 1 treatment course group and 2 treatment courses group (72.73%(136/187) vs.55.47%(71/128) and 58.71%(155/264), 72.73%(40/55) vs.6/15 and 47.83%(11/23)), the effective rate of autism in 3 treatment courses group was higher than that in 1 treatment course group (69.05%(29/42) vs. 6/15), and the differences were statistically significant ( χ2=10.05, 9.39, 5.60, 4.44 and 3.94, all P<0.05). Conclusions:The long-time efficacy of FMT is definite in the treatment of intestinal flora derangement related intestinal diseases and extraintestinal diseases complicated with intestinal disfunction and there are no serious adverse events. The efficacy of FMT is related to the way of transplantation and treatment. The incidence of complications of FMT is related to the way of transplantation. Different ways of transplantation and treatment courses should be formulated for different diseases.