Three 2,3-diketoquinoxaline alkaloids with hepatoprotective activity from Heterosmilax yunnanensis / 药学学报

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Research progress of dysthyroid optic neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

Dysthyroid optic neuropathy is an important secondary pathological condition of thyroid-associated ophthalmopathy, characterized clinically by several clinical manifestations, including reduced visual acuity, impairment of color vision, relative afferent pupillary defect, and optic disk edema or atrophy. Ophthalmological auxiliary examination shows abnormal vision field and visual evoked potential, etc., and imagining examination shows orbital apex crowding, which can assist diagnosis. The pathogenesis of this disease is still unclear. With previous studies proposing that it was related to optic nerve compression, stretch, and ischemia. Treatment methods include high-dose intravenous glucocorticoid, orbital decompression, orbital radiation therapy, and biological agent. This article systematically reviews the research progress on the epidemiological characteristics, pathogenesis, diagnosis, and treatment of this disease, with a view to providing useful reference for future in-depth clinical practice and scientific research.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Study on improvement effect mechanism of Xibining prescription on knee osteoarthritis model rats based on AMPK/mTOR signaling pathway / 中国药房

OBJECTIVE To investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Totally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP- 13， and the phosphorylation level of AMPK and mTOR proteins were detected. RESULTS Compared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained，the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）. CONCLUSIONS XBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.

Research progress of influenza vaccination, pneumococcal vaccination and COVID-19 vaccination among cancer patients / 中华预防医学杂志

This article reviews the relevant studies on the efficacy and safety of influenza, pneumococcal and COVID-19 vaccination among tumor patients worldwide in recent years. By combing and analyzing the retrieved literature, the results show that influenza and pneumococcal vaccination can significantly reduce the morbidity and hospitalization rate of infectious diseases in tumor patients, reduce the risk of cardiovascular events and death, and significantly improve survival prognosis. COVID-19 vaccination can also protect tumor patients, especially those who have completed full dose vaccination. Authoritative guidelines and consensuses worldwide all recommend that tumor patients receive influenza, pneumococcal and COVID-19 vaccines. We should carry out relevant researches, as well as take effective measures to strengthen patient education, so that tumor patients can fully experience the health protection brought by the vaccine to this specific group.

Clinical comprehensive evaluation of Chinese patent medicine for the treatment of chronic hepatitis B / 中国药房

OBJECTIVE To compare the clinical comprehensive value of 15 Chinese patent medicines for the treatment of chronic hepatitis B， in order to provide reference for clinical rational drug use. METHODS According to the Management Guidelines for Clinical Comprehensive Evaluation of Pharmaceuticals （2021 Version for Trial Implementation）， systematic literature review， meta-analysis and other related data analysis methods were used to perform qualitative and quantitative analysis for the safety， efficacy， economy， suitability， accessibility and innovation of 15 Chinese patent medicines. RESULTS In terms of safety， most of the adverse drug reactions of chronic hepatitis B Chinese patent medicines before the market were unobserved or unclear； post-marketing safety took nucleoside analogs as the intermediate bridge for meta-analysis， there was no significant difference in the incidence of adverse drug reactions among the combined regimens of Chinese patent medicines （P＞0.05）， except that the combination regimen of Fuzheng huayu capsule， Compound yiganling capsules versus combination regimen of Jiuwei gantai capsules showed statistically significant differences （P＜0.05）. In terms of effectiveness， the results of network meta-analysis showed that most Chinese patent medicines， such as Fuzheng huayu capsules combined regimens， had no significant differences in effective rate， HBeAg negative conversion rate and HBV-DNA negative conversion rate （P＞0.05）； however， in reducing the liver elastic hardness value， the combined regimen of Dangfei liganning tablet （capsule） was better than the other combined regimens （P＜0.05）. In terms of economy， the highest cost was the Shuganning injection， and the lowest was Hepatitis B qingre jiedu granules. In terms of suitability， most of the medicines were capsules， tablets and granules， which only needed to be sealed to store and taken orally or taken with boiling water. Compared with injections and some similar products that required strict control of storage temperature， its suitability was better. In terms of accessibility， from the perspective of drug price and affordability， Shuganning injection had the highest average daily cost， the number of days that needed to be borne by the average daily wage was the highest； the average daily cost of Compound yiganling tablets was the lowest， and the number of days required to be borne by the average daily wage was the lowest. From the perspective of availability， Compound biejia ruangan tablets， Dangfei liganning capsules and Wuzhi granules were easier to obtain. In terms of innovation， the 15 Chinese patent medicines included in the study were all domestically produced medicines with a relatively long-term theoretical basis of traditional Chinese medicine and experience in human medicine， and had good industrial innovation. Among them， Compound huayu tablets （capsules） and Anluo huaxian pills were protected varieties of traditional Chinese medicine； Fuzheng huayu tablets （capsules） with more patents had 6 valid patents， all of which were patents for invention. CONCLUSIONS Wuzhi capsule， Sedum sarmentosum granules， Compound yiganling tablets， Rhubarb buchong pills and Dangfei liganning capsules have high clinical comprehensive value.

Advances in immune checkpoint inhibitors combined with other treatments / 中国药科大学学报

@#As one of the most attention-attracting immunotherapy, immune checkpoint inhibitors (ICIs) have been approved as the first-line drugs for the therapy of various types of cancers.Nevertheless, the single application of ICIs exhibited limited efficacy, and it is easy to develop drug resistance.Therefore, the development of combination therapies become a hot topic in this field to improve the efficacy of ICIs therapy.This article describes some new ICIs targets, reveals the mechanisms of resistance, and introduces the current status of combination other therapies with ICIs therapy systematically including chemotherapy, radiotherapy, hyperthermia, antiangiogenic therapy, tumor vaccines, cytokine therapy and adoptive cellular therapy.Furthermore, the synergistic mechanism of combination therapy to enhance antitumor effect.Thus, this article provides solid references for personalized combination therapy according to the pathological characteristics of patients.

Effects of Decitabine Combined with Anlotinib on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the biological effects and its relative mechanism of decitabine combined with anlotinib on multiple myeloma cells.@*METHODS@#The human MM cell lines and primary cells were treated with different concentrations of decitabine, anlotinib, and decitabine+anlotinib, respectively. The cell viability was detected and combination effect was calculated by CCK-8 assay. The apoptosis rate was measured by flow cytometry and the level of c-Myc protein was determined by Western blot.@*RESULTS@#Both decitabine and anlotinib could effectively inhibit the proliferation and induce the apoptosis of MM cell lines NCI-H929 and RPMI-8226. The effect of combined treatment on the inhibition of cell proliferation and induction of apoptosis was stronger than that of single-drug treatment. The combination of the two drugs also showed strong cytotoxicity in primary MM cells. Decitabine and anlotinib could down-regulate the level of c-Myc protein in MM cells and the c-Myc level in the combination group was the lowest.@*CONCLUSION@#Decitabine combined with anlotinib can effectively inhibit the proliferation and induce apoptosis of MM cells, which provides a certain experimental basis for the treatment of human MM.

Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.@*METHODS@#This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.@*RESULTS@#STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.@*CONCLUSION@#The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Effect of intervention based on theory of planned behavior on muscle attenuation and balance of the elderly with sarcopenia / 中国康复理论与实践

ObjectiveTo explore the effect of intervention based on theory of planned behavior on muscle attenuation and balance of the elderly with sarcopenia. MethodsFrom September, 2022 to February, 2023, 124 elderly people with sarcopenia were conveniently sampled from Lishuiwan Community and Shuxiangyuan Community in Shijiazhuang City, Hebei Province. According to the coin toss, 62 elderly people from Shuxiangyuan Community were designated as control group, and 62 elderly people from Lishuiwan Community were as intervention group. The intervention group implemented the intervention based on the theory of planned behavior, including behavior attitude, behavior, subjective norms, perceived behavior control and behavior awareness; the control group maintained their original lifestyle, for twelve weeks. Before and after intervention, the grip strength, time of Five-Times-Sit-to-Stand Test, relative appendicular skeletal muscle index (RASM), 6-minute walking speed and the score of Berg Balance Scale (BBS) were compared. ResultsAfter intervention, the grip strength, RASM, 6-minute walking speed, and the score of BBS significantly increased, and the time of Five-Times-Sit-to-Stand Test shortened in the intervention group (|Z| > 6.257, |t| > 28.643, P < 0.001), and they were better in the intervention group than in the control group (|Z| > 2.288, |t| > 3.177, P < 0.05). ConclusionThe intervention based on theory of planned behavior can effectively relieve the muscle attenuation of the elderly with sarcopenia, and improve their balance ability.

Congenital hypothyroidism in preterm infants:analysis of factors in the pathogenesis and clinical prognosis / 中国新生儿科杂志

Objective:To investigate the characteristics of congenital hypothyroidism (CH) in premature infants and analyze the predictors of transient congenital hypothyroidism(TCH) and permanent CH (PCH).Methods:A retrospective study was conducted on the preterm infants with CH born in Beijing from January 2008 to June 2018. They were screened, diagnosed and treated by the Beijing Neonatal Disease Screening Center. They were assigned into TCH and PCH groups according to the clinical prognosis. Univariate analysis and Logistic regression analyses were used to determine the predictors of PCH, and the receiver operating characteristic curve (ROC) was drawn to determine the best cut-off point.Results:A total of 2 216 892 newborns were screened, 15 382 were initially screened positive, the median time of screening was 4(4,10) d after birth, and the median time of postnatal reexamination was 30(22,42) d after birth, 14 576 newborns were reexamined, the reexamination rate was 94.8%. A total of 92 preterm infants were diagnosed with CH, of which 60 were TCH, accounting for 65.2%; 28 were PCH, accounting for 30.4%; and 4 were lost to follow-up, accounting for 4.3%. Univariate analysis showed that in the PCH group, the abnormal rate of thyroid B-ultrasound, levothyroxine (LT4) dose at 1-year old, thyrotropin (TSH) level at 2 years old, LT4 dose at 2 years old, LT4 dose and free thyroxine (FT4) level at 3 years old were higher than those in the TCH group. Logistic regression analysis revealed that abnormal B-ultrasound ( OR=12.184,95% CI 2.270~65.403), and elevated TSH level at 2 years old ( OR=2.033,95% CI 1.280~3.228),increased LT4 dose at 3 year old ( OR=21.435,95% CI 3.439~133.584) are the risk factors for PCH. The maximum area under ROC curve was 0.798 at 3 years old (95% CI 0.680~0.916), the best cut-off point was 1.3 μg/(kg·d) for the 3-year-old drug dose; followed by 2-year-old TSH level, which was 0.683 (95% CI 0.548~0.817), the best cut-off point was 4.51 μIU/ml. Conclusions:TCH accounted for a large proportion of preterm infants with CH. During the follow-up, the increased LT4 dose at 3 years old and the elevated TSH level at 2 years old were the early predictors of PCH.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, aiming to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis as well as treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history.All of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.During the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all three patients, the protein level was significantly increased, and there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combining with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of the patients.

Clinical features of three children with severe COVID-19 encephalopathy and literature review / 中国小儿急救医学

Objective:To analyze the clinical characteristics, diagnosis and treatment of 3 children with severe COVID-19 encephalopathy, targeted to improve the clinicians′ understanding of the disease.Methods:The clinical features, laboratory examinations, imaging data and diagnosis and treatment process of 3 cases of severe COVID-19 encephalopathy admitted to the Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University from December 1, 2022 to December 31, 2022 were retrospectively analyzed.Results:Among the 3 patients, 2 were female, age was 2-11 years old, all of them had 2-3 days of medical history, all of them had clinical manifestations of high fever(≥40 ℃), convulsions and consciousness disorders, nucleic acid and antigen tests of SARS-CoV-2 were positive, and mycoplasma pneumonia IgM antibody was positive in 1 case.Within 24 hours after admission, the levels of white blood cells were basically normal, neutrophil fraction was dominant, and procalcitonin was significantly increased.Total T cells and NK cells in the blood of the three patients were significantly decreased, and the levels of blood ammonia, blood glucose and bilirubin were basically normal.In the early stage of the disease, the cell counts of the cerebrospinal fluid was normal in all the three patients, the protein level was significantly increased, there were new symmetrical lesions on head magnetic resonance imaging in 3 patients.After symptomatic treatment and immunotherapy including early use of hormone, human gamma globulin and plasma exchange, all the patients were survived, but had different degrees of new dysfunction of the nervous system.Conclusion:Severe COVID-19 encephalopathy can occur in the acute phase of SARS-CoV-2 infection, mostly manifested as high fever, convulsions and severe disturbance of consciousness, combined with multiple organ dysfunction and irreversible nervous system damage.Early supportive treatment, brain protective treatment and immunotherapy are helpful to improve the prognosis of patients.

Chemical constituents and mechanism of Chuanzhi Tongluo Capsules based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology / 中国中药杂志

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.

Optimization of the extraction technology for the raw drugs of Sanse powder gel paste / 中国药房

OBJECTIVE To optimize the extraction technology for the raw drugs of Sanse powder gel paste. METHODS SD rats were divided into blank group， model group， traditional technology group， water extraction group and ethanol extraction group， with 5 rats in each group. Anterior cruciate ligament transection was used to construct knee osteoarthritis model， and the pharmacodynamic effects of different extraction methods on arthritic rats were investigated. Analgesic experiments were conducted using cold and hot pain thresholds and pain mediators calcitonin gene-related peptide （CGRP）， cyclooxygenase-2 （COX-2）， substance P （SP）， and prostaglandin E2 （PGE2） contents as indicators. HE staining was performed on the synovial membrane of rats to observe the degree of synovial cell proliferation， inflammatory infiltration and vascular invasion， and anti-inflammatory experiments were conducted using protein and mRNA expressions of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α） and IL-6 as indicators. The analgesic and anti-inflammatory effects were compared among those groups. In the orthogonal test， ethanol dosage， extraction time and extraction times were used as evaluation factors， and the contents of casticin， strychnine and toxiferine were taken as evaluation indicators； comprehensive score was calculated. The validation experiments were carried out after optimizing the extraction technology of the raw drugs of Sanse powder gel paste. RESULTS Compared with the model group， the cold and heat pain thresholds of drug administration groups （except for the traditional technology group） were all increased significantly （P＜0.05）， while the contents of pain （No.Y2021rc02） mediators CGRP， COX-2， SP and PGE2 were all decreased significantly （P＜0.05）. HE staining showed that inflammatory cell infiltration， fibrosis and collagen deposition were 炎。E-mail：liuzixiu3221@126.com decreased in the administration groups； a small amount of capillary proliferation could be found； the protein and mRNA expressions of inflammatory factors such as IL-1β， IL-6 and TNF-α were decreased significantly in synovial tissue of rats in administration groups （P＜0.05）. Compared with the traditional technology group， most indicators of the ethanol extraction group were significantly reduced （P＜0.05）， and only heat pain threshold and mRNA expression of IL-6 in rats were decreased significantly in the water extraction group （P＜0.05）. The optimal extraction technology of the raw drugs of Sanse powder gel paste included suitable dose of Sanse powder， 8-fold 55% ethanol， heating reflux extraction for 90 minutes， extracting twice. The results of 3 times of verification experiments showed that the average contents of casticin， strychnine and toxiferine were 0.007%， 0.092%， and 0.214%， respectively； RSD were all less than 5%. CONCLUSIONS The optimized extraction technology for the raw drugs of Sanse powder gel paste is stable and feasible， which can improve the efficacy of the preparation.

Research progress of microRNA in proliferative vitreoretinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Proliferative vitreoretinopathy(PVR)is a eye disease characterized by the formation of epiretinal membranes(ERM)composed of extracellular matrix(ECM)and various types of cells in the vitreous and/or the surface of the retina through the wound repair and fibrotic process. ERM shrinks to form retinal folds and stretches the retina to cause retinal detachment(RD). Epithelial-mesenchymal transition(EMT)of retinal pigment epithelial(RPE)cells and accumulation of ECM are considered to be the main pathological mechanisms for the formation of ERM. RPE cells undergo a process named EMT induced by transforming growth factor-β(TGF-β), by which differentiated epithelial cells go through epithelial phenotypic loss, the weakness of cell-cell contact and mesenchymal phenotype expression. Fibroblast-like cells differentiated from mesenchymal cells produce ECM and other components, which forms ERM together with glial cells and fibroblasts, <i>etc</i>. Recent studies indicated a lot of cytokines/growth factors, transcriptional factors, and microRNA(miRNA)regulate the development of EMT in RPE cells, in which miRNA is a novel and powerful regulatory gene and plays a critical regulatory role in the EMT process of PVR. This review focuses on the current understandings of the mechanism and the interventional treatments of miRNA in PVR.

Preliminary study on calculating size-specific dose estimate values based on age in children′s head / 中华放射医学与防护杂志

Objective:To investigate the feasibility of size-specific dose estimate of head based on pediatric patients′ age.Methods:A retrospective study was conducted on plain head CT scans of 210 patients in Tianjin Children′s Hospital from January to March in 2022. The volume CT dose index (CTDI vol) values, age and sex of the patients were recorded. The anteroposterior diameter (AP) and lateral diameter(LAT), aera and CT value in the middle slice of the scan region were measured on the workspace. According to the AAPM reports 220 and 293, the water equivalent diameter ( DW) of head, size-specific conversion factors ( fmeasuredH16), and size-specific dose estimate (SSDE measured) were calculated. The effective diameter ( Deff; WHO) was calculated for male and female individuals using the ralationship between the standard head circumference and age of children provided by World Health Organization (WHO). The effective diameter ( Deff; WHO) was converted into a water equivalent diameter ( DW; WHO), using a correlation established from the Deff and DWwhich were measured in 210 image sets of male and female patients. Then the corresponding fWHOH16 and SSDE WHO of head can be calculated. The correlation between DW and DW; WHO, fmeasuredH16 and fWHOH16, the correlation and consistency between SSDE measured and SSDE WHO, and the conversion relationship between age and fWHOH16 were analyzed for male and female patients. Results:A significant correlation were found between the measured DW and DW; WHO(female: r=0.917, P<0.01; male: r=0.873, P<0.01), fmeasuredH16 and fWHOH16(female: r=0.916, P<0.01; male: r=0.883, P<0.01), SSDE measured and SSDE WHO( r=0.991, P<0.01; male: r=0.992, P<0.01). The Bland-Altman test indicated that there was good coherence between SSDE measured and SSDE WHO. Maximal mean root-mean-square errors of SSDE measured and SSDE WHO were 5.61% in female and 5.25% in male. The conversion relationship between fWHOH16 and patient age in different genders was obtained by curve fitting. Conclusion:The SSDE of head in pediatric patients can be estimated simply and accurately by directly using the patient′s age.

Effect of selective feticide at different gestational weeks in double chorionic twin pregnancies on pregnant women and perineonates outcomes / 中国医师进修杂志

Objective:To compare and analyze the pregnant women and perineonates outcomes of selective feticide at different gestational weeks in double chorionic twin pregnancies.Methods:The clinical data of 86 patients with double chorionic twin pregnancies who underwent selective feticide from January 2015 to June 2021 in the General Hospital of Northern War Zone were retrospectively analyzed. The patients were divided into two groups according to different gestational weeks of selective feticide: 23 cases at 14 +3 to 19 +6 gestational weeks (group A), 31 cases at 20 to 27 +6 gestational weeks (group B), 32 cases and at ≥28 gestational weeks (group C). The gestational weeks of delivery, abortion, preterm birth, full-term birth, liveborn infants, surviving infants, birth body mass of liveborn infants, birth body mass of surviving infants, complications in pregnant women, pregnant women and perineonates outcomes and neonatal prognosis were recorded. Results:There were no statistical differences in gestational weeks of delivery, incidence of complications in pregnant women, abortion rate and neonatal survival rate among three groups ( P>0.05); there were statistical differences in preterm birth rate, full-term birth rate, liveborn infants rate, birth body mass of liveborn infants and birth body mass of surviving infants among three groups ( P<0.05). The preterm birth rate in group A was significantly lower than that in group C: 21.7% (5/23) vs. 68.8% (22/32), the full-term birth rate was significantly higher than that in group C: 69.6% (16/23) vs. 28.1% (9/32); the birth body mass of liveborn infants and birth body mass of surviving infants in group A were significantly higher than those in group B and group C: (2 905.7 ± 580.9) g vs. (2 284.4 ± 416.7) and (2 293.8 ± 456.2) g, (2 905.7 ± 580.9) g vs. (2 457.1 ± 527.8) and (2 359.2 ± 482.4) g, the liveborn infants rate in group C was significantly higher than that in group B: 96.9% (31/32) vs. 77.4% (24/31), and there were statistical differences ( P<0.05). The 72 surviving infants were followed up for 3 months to 4 years, and no motor dysfunction and neurological abnormalities occurred. Conclusions:Selective feticide in patients with double chorionic twin pregnancies before 20 weeks of gestation has less complications in pregnant women and good perineonates clinical outcome.

Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020 / 中国临床药理学与治疗学

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Bioinformatics analysis on structure and function and expression vector construction of SARS-CoV-2 related protein TMPRSS2 / 中国药理学通报

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.