Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Application of structured guided feedback in the clinical practice of cardiology nursing students / 中华医学教育探索杂志

Objective:To explore the value of structured guided feedback in improving the clinical skills and teaching effect of the cardiology practice nursing students.Methods:A total of 60 nursing students of Batch 2018 in the Department of Cardiology were selected as the control group, and guided feedback methods were used. Another 60 nursing students of Batch 2019 were collected as the research group, using structured guided feedback methods. After the clinical teaching of the intern nurses, the clinical skills (nursing operation skills, communication skills, condition observation and handling, emergency response ability, team collaboration and clinical decision-making) and the teaching effect were evaluated by theoretical assessment and case scenario simulation exercise assessment scores and self-assessment scales. SPSS 22.0 was performed for t test. Results:The theoretical assessment and scenario simulation exercise assessment scores of the research group were significantly higher than those of the control group [(91.30±2.42) vs. (94.62±2.28); (89.06±3.35) vs. (93.11±3.40)] ( P<0.05). The clinical skills (nursing operation skills, communication skills, condition observation and handling, emergency response ability, team collaboration and clinical decision-making) and teaching effect scores of the nursing students in the study group were significantly better than those of the control group ( P<0.05). Conclusion:The application of problem-based learning combined with scenario simulation teaching under the structured guided feedback in the nursing teaching of cardiology practice nurses can further promote the clinical skills of the practice nurses and improve the teaching effect.

The effect of PAD class on improving the practical ability of dermatovenereology residents / 中华医学教育探索杂志

Objective:To study the effect of PAD (presentation-assimilation-discussion) class applied in the standardized residency training of dermatovenereology on improving residents' practical operation ability.Methods:A total of 120 residents taking the standardized residency training of dermatovenereology in the Affiliated Hospital of North Sichuan Medical College from November 2018 to December 2020 were selected as the research objects and divided into two groups according to the time order of admission, among which, 60 residents enrolled from November 2018 to November 2019 were selected as the control group, and 60 residents enrolled from December 2019 to December 2020 were selected as the experimental group. The control group adopted the traditional standardized residency training mode, and the experimental group adopted the teaching mode of PAD class. SPSS 22.0 statistical software was used for data analysis. The results of theoretical knowledge assessment and skill operation assessment were compared between the two groups by t test, the evaluation of teaching effect was compared between the two groups by chi-square test, and the satisfaction of teaching was compared between the two groups by rank sum test. Results:The theoretical knowledge [(45.38±4.14) points], skill operation [(42.35±4.32) points] and total score [(88.74± 7.69) points] of the experimental group were higher than those of the control group [(39.62 ± 4.15) points, (36.25±4.27) points, (77.96±7.52) points, respectively], with statistical significance ( P<0.05). The evaluation of teaching effect in the experimental group showed that 49 residents (81.67%) believed that their learning interest had been stimulated; 51(85.00%) improved their self-learning ability; 47(78.33%)improved their ability of analyzing and solving problems; 50(83.33%) improved their doctor-patient communication ability; 49(81.67%) improved their clinical thinking ability; 52(86.67%) improved their teamwork ability; and 50(83.33%) improved their literature retrieval ability. The results of satisfaction showed that the experimental group was significantly higher than the control group in sense of responsibility, teaching methods, teaching contents and self-evaluation. Conclusion:The application of PAD class in the standardized residency training of dermatovenereology plays a positive role in mobilizing the learning enthusiasm of residents and cultivating their independent learning ability, and can significantly improve the practical operation and theoretical awareness of residents.

Design and application of oral administration aid for methotrexate / 中国实用护理杂志

Objective:To design an oral methotrexate auxiliary device and explore the effect of methotrexate in patients with rheumatoid arthritis.Methods:Totally 30 patients with rheumatoid arthritis were selected and observed continuously for 12 months, from January to June in 2021, in the Affiliated Changzhou No. 2 People ′s Hospital of Naijing Medical University. The subjects took the medicine routinely in the first 6 months after entering the group, and the methotrexate oral drug assistant device was given in the latter 6 months to remind them to take the medicine correctly. Medication administration of patients before and after using the auxiliary device was compared, and the evaluation indexes such as disease activity, medication compliance and anxiety were observed. Results:Without the auxiliary device, there were 14 cases (46.67%) of medication error, 13 cases (43.33%) of medication time error, 9 cases (30.00%) of missed administration, while after the use of the auxiliary device, there were 4 cases (13.33%) of medication error, 2 cases (6.67%) of medication time error and 2 cases (6.67%) of missed administration, and the differences were statistically significant ( χ2=8.10, 9.09, 5.14, all P<0.05). Moreover, before using the auxiliary device, the scores of disease activity and medication compliance were 3.92 ± 0.95, 84.97 ± 6.49, respectively, while with the help of the auxiliary device, those scores changed to 3.29 ± 0.83, 92.40 ± 4.17 respectively. All the differences were statistically significant ( t=10.06, -10.37, both P<0.01). 16 cases (53.33%) were anxious after using the assistive device, which was also better than 26 cases (86.67%) before using the device. The difference was statistically significant ( χ2=8.10, P<0.01) . Conclusions:Oral administration aid for methotrexate can help rheumatoid arthritis patients to take methotrexate correctly and safely, reducing disease activity and anxiety, improving drug compliance. It is worthy to clinical promotion.

Investigation on prevalence of Schistosoma japonicum infections in wild mice in Shitai County, Anhui Province, 2018 / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Schistosoma japonicum infection in wild mice in Shitai County, Anhui Province, so as to provide insights into precise control of the source of S. japonicum infections. Methods Wild mice were captured using the trapping method for three successive nights at snail-infested settings from Jitan Village of Jitan Township, and Shiquan Village and Xibai Village of Dingxiang Township, Shitai County, Anhui Province in June and October, 2018. All trapped wild mice were sacrificed and liver and mesenteric vein specimens were collected for detection of S. japonicum eggs using microscopy, while the fecal samples in mouse intestines were collected for identification of S. japonicum infections using Kato-Katz technique. In addition, the population density of trapped wild mice was estimated and the prevalence of S. japonicum infection was calculated in trapped wild mice. Results A total of 376 wild mice were trapped from three villages in Shitai County. The population density of trapped wild mice was 9.1% (376/4 124), and the prevalence of S. japonicum infection was 24.2% (91/376) in trapped wild mice. The highest prevalence of S. japonicum infection was detected in Shiquan Village of Dingxiang Township (30.1%), and the lowest prevalence was seen in Xibai Village of Dingxiang Township; however, there was no significant difference in the prevalence of S. japonicum infection in trapped wild mice among three villages (χ2= 4.111, P > 0.05). In addition, there was no significant difference in the prevalence of S. japonicum infection in wild mice captured between on June (26.8%, 34/127) and October (22.9%, 57/249) (χ2 = 0.690, P = 0.406). The trapped wild mice included 6 species, including Rattus norvegicus, Niviventer niviventer, R. losea, Apodemus agrarius, Mus musculus and N. coning, and the two highest prevalence of S. japonicum infection was detected in R. losea (34.9%, 22/63) and R. norvegicus (31.2%, 44/141). Conclusions The prevalence of S. japonicum infections is high in wild mice in Shitai County, and there is a natural focus of schistosomiasis transmission in Shitai County.

The ocular clinical features and treatment of 18 cases young infants with incontinentia pigmenti / 中华眼底病杂志

Objective:To observe the ocular clinical features and efficacy of young infants with incontinentia pigmenti (IP).Methods:A retrospective study. Clinical data of 18 young infants with IP aged 0-3 months in the Department of Ophthalmology of Henan Children's Hospital from October 2017 to February 2019 were collected in this study. All patients were underwent fundus examination under topical anesthesia or general anesthesia. Among them, 9 cases were underwent genetic testing. Patients were determined whether to treated with retinal laser photocoagulation (LIO) or intravitreal conbercept (IVC, 0.25 mg/0.025 ml) according to the condition of eyes. The followed-up time ranged from 4months to 43 months. The ocular clinical features and treatment were observed.Results:There were 1 male and 17 females of the 18 patients. The age of first visit were 1.2±1.0 months (2 d-3 months). All cases had typical skin lesions, 4 cases had neurological symptoms, 10 cases had tooth abnormalities, and 4 cases had cicatricial alopecia. Among the 9 cases that were underwent genetic testing, 5 cases were deleted in exons 4-10 of the IKBKG gene and 1 case were a heterozygous mutation c.1124delT in exon 9 of the IKBKG gene. Among the 36 eyes, 21 eyes of 13 cases with incontinentia pigmenti-associated ocular diseases were all retinopathy (58.3%,21/36). Retinopathy of 9 cases were asymmetrical (69.2%,9/13). Among the 21 eyes, 3 eyes were simple retinal pigment abnormalities (14.3%,3/21) and 18 cases had retinal vascular lesion (85.7%, 18/21). Among the 36 eyes, 8 eyes were treated; 4 eyes were underwent LIO; 3 eyes were treated with IVC; 1 eye was treated with LIO combined with IVC. They were all improved significantly after the operation without serious complications. 1 eye with retinal detachment did not undergo surgical treatment due to guardian reasons. Perceptual exotropia and eyeball atrophy was found during the follow-up. Conclusions:The onset of IP-related ocular anomalies is early. The early anomalies were mainly retinal vascular abnormalities. Treatment in early time is effective.

Inhibitory Effect of Liuwei Dihuangwan on Triple-negative Breast Cancer Through MAPKKK1 and KLF4 / 中国实验方剂学杂志

ObjectiveTo study the underlying mechanism of Liuwei Dihuangwan in inhibiting triple-negative breast cancer through mitogen-activated protein kinase kinase kinase 1 （MAPKKK1） and Krüppel-like factor 4 （KLF4）. MethodFour hundreds SPF female Kunming mice aged 11.5 months were palpated once every 3 days. The model mice of spontaneous tumors were randomly divided into a model group （normal saline）， a paclitaxel group （0.025 g·kg-1·d-1， ip， 21 days）， and high-， medium- and low-dose Liuwei Dihuangwan groups （7.2， 3.6， 1.8 g·kg-1·d-1， ig）. Tumor tissues were separated until the moribund stage. The tumor volume and weight were measured， and the tumor inhibition rate and the survival time of the tumor mice were calculated （after 6 months， tumor-free mice were assigned into the normal group）. SPF SD rats were selected to prepare serum samples containing Liuwei Dihuangwan of different concentrations for cell culture， and MAPKKK1 in MDA-MB-231 cells was silenced. The protein expression of MAPKKK1 and KLF4 was detected by immunofluorescence and Western blot. ResultThe in vivo experimental results showed that compared with the conditions of the normal group， the protein expression of MAPKKK1 and KLF4 in tumor tissues of the model group dropped （P<0.01）. Compared with the model group， all medication groups showed reduced tumor volume and weight （P<0.05， P<0.01）， increased tumor inhibition rate， prolonged survival time of tumor mice （P<0.05）， and increased protein expression of MAPKKK1 （P<0.01）. Additionally， the paclitaxel group and the high-dose Liuwei Dihuangwan group exhibited increased protein expression of KLF4 （P<0.01）. The in vitro experiments showed that compared with the conditions of the normal group， the fluorescence intensities of MAPKKK1 and KLF4 in MDA-MB-231 cells in all medication groups were potentiated， and the protein expression of MAPKKK1 in the paclitaxel group and the high- and medium-dose Liuwei Dihuangwan groups， and the protein expression of KLF4 in the paclitaxel group and high-dose Liuwei Dihuangwan group increased （P<0.01）. After silencing of MAPKKK1， compared with the conditions of the negative plasmid group （unsilenced MAPKKK1）， the fluorescence intensities of MAPKKK1 and KLF4 and the protein expression decreased in the RNAi-27 positive plasmid group （silenced MAPKKK1） （P<0.05， P<0.01）. Compared with the RNAi-27 positive plasmid group， all medication groups had enhanced fluorescence intensities of MAPKKK1 and KLF4 and protein expression to different degrees （P<0.05， P<0.01）. ConclusionLiuwei Dihuangwan can inhibit the growth of triple-negative breast cancer， and the underlying molecular mechanism is related to the up-regulation of MAPKKK1 and activation of KLF4 expression.

Effective Components of Periploca forrestii Against Rheumatoid Arthritis by Targeting TNF-α / 中国实验方剂学杂志

ObjectiveTo analyze the effective components of Periploca forrestii against rheumatoid arthritis（RA）by targeting tumor necrosis factor （TNF）-α based on network pharmacology and experimental verification. MethodThe preliminary research of the research group found that the alcohol extracts of P. forrestii （CDLF and CQAF） had significant anti-RA activities，and 10 monomers with such activities were identified. The anti-RA activities of active monomers，CDLF， and CQAF were compared by the enzyme-linked immunosorbent assay （ELISA）with interleukin（IL）-6，nitric oxide （NO），IL-1β， and prostaglandin E2（PGE2）as indicators. Network pharmacology was employed to analyze the possible molecular mechanism of P. forrestii against RA. The targeting ability of P. forrestii chemical monomers to TNF-α was verified by TNF-α molecular docking，surface plasmon resonance （SPR）， and TNF-α-induced L929 injury model. ResultELISA showed that the anti-RA activities of CDLF and CQAF were significantly stronger than those of identified 10 active monomers. Network pharmacology analysis showed that the core targets of P. forrestii against RA were signal transducer and activator of transcription protein 3 （STAT3），TNF， and IL-6. Gene Ontology（GO） analysis revealed collagen catabolism，inflammatory response，positive regulation of nuclear factor kappa-B（NF-κB） transcription factor activity，and positive regulation of B cell proliferation. Kyoto Encyclopedia of Genes and Genomes （EKGG） pathway enrichment analysis demonstrated TNF signaling pathway，phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway，NF-κB signaling pathway，Toll-like receptor signaling pathway，mitogen-activated protein kinase（MAPK） signaling pathway， etc. Verification experiments by TNF-α molecular docking，SPR， and TNF-α-induced L929 injury model found that CDLF and CQAF had good binding activities and could manifestly antagonize TNF-α. However， the active components separated and identified from CDLF and CQAF did not show the same anti-TNF-α activity. ConclusionThe CDLF and CQAF of P. forrestii may treat RA by targeting TNF-α. The experiments found that the isolated chemical components had weaker binding activity to TNF-α than CDLF and CQAF. Meanwhile，the research group isolated chemical components with a minimum mass fraction of 0.25 ng·g-1 from P. forrestii， which suggested that the active components generated by binding to TNF-α with anti-RA activities were presumedly trace components .

Effect of Fufang Shelong Capsules on Rats with Membranous Nephropathy Based on p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the nephroprotective and anti-inflammatory effects of Fufang Shelong capsules （FFSL） in rats with membranous nephropathy （MN）， and the role of the p38 mitogen-activated protein kinase （MAPK） signaling pathway. MethodMale SD rats of SPF grade were divided into a normal group and an experimental group. The MN model was induced by tail vein injection of cationized bovine serum albumin in the experimental group. After screening， the eligible model rats were included and divided into a positive control group （tripterygium glycosides tablets） and low-， medium-， and high-dose FFSL groups （0.375， 0.75， 1.5g·kg-1）. The rats were treated correspondingly for eight weeks， and urine protein was detected during drug intervention. Renal function and inflammation-related indicators were detected after drug intervention. The changes in 24-hour urine total protein （24 h UP）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， creatinine （Cr）， blood urea nitrogen （BUN）， total protein （TP）， albumin （Alb）， and total cholesterol （TC） were detected. Flow cytometry was used to detect CD4+/CD8+ changes. Kidney tissues were collected to observe pathological changes under a light microscope and an electron microscope. The protein expression of p38 MAPK and phosphorylated p38 MAPK （p-p38 MAPK） in kidney tissues was detected by Western blot. ResultCompared with the normal group， the model group showed increased 24 h UP （P<0.01）， elevated serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， decreased serum Alb and TP levels （P<0.05，P<0.01）， increased CD4+/CD8+ in the peripheral blood （P<0.01）， and up-regulated protein expression of p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05）. Additionally， in the model group， immune complex deposition and foot process fusion， accompanied by infiltration of inflammatory cells， were observed on the epithelial side of the basement membrane in the pathological kidney tissues. Compared with the model group， the groups with drug intervention showed declining 24 h UP levels at six weeks （P<0.05，P<0.01）， decreased serum Cr， BUN， TC， IL-6， IL-8， and TNF-α （P<0.05，P<0.01）， increased serum Alb and TP levels （P<0.05，P<0.01）， reduced CD4+/CD8+ in the peripheral blood （P<0.01）， improved renal pathological damage， and down-regulated p38 MAPK and p-p38 MAPK in kidney tissues （P<0.05，P<0.01）. ConclusionFFSL can decrease the expression of inflammatory factors， reduce proteinuria， delay kidney damage， and protect kidney function by inhibiting the expression of the p38 MAPK signaling pathway.

Proteomics Analysis of Mechanism of Shenxiong Glucose Injection in Antagonizing H2O2-Induced Oxidative Damage in H9c2 Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Shenxiong glucose injection （SGI） in inhibiting hydrogen peroxide （H2O2）-induced oxidative damage in H9c2 cells by tandem mass tags （TMT）-labeled quantitative proteomics. MethodH9c2 cells cultured in vitro were exposed to H2O2 for inducing oxidative damage. The cell viability was measured by cell proliferation and cytotoxicity assay （MTS）， followed by peptide fractionation by high performance liquid chromatography （HPLC） and protein expression detection in H9c2 cells by ultrahigh performance liquid chromatography-mass spectrometry. MaxQuant （v1.5.2.8） was utilized for data retrieval， and the high-resolution mass spectrometry was conducted to screen out differentially expressed proteins， which were then subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The protein expression levels of perilipin 2 （Plin2） and tropomyosin 1 （Tpm1） in cells were measured by Western blot. ResultThe spectral analysis yielded 48 608 specific peptide fragments and 5 903 quantifiable proteins. Compared with the model group，the SGI group exhibited 82 differentially expressed proteins，of which 22 were up-regulated and 60 were down-regulated. GO analysis results showed that the differentially expressed proteins were mainly involved in biological processes such as programmed cell death regulation，regulation of cell proliferation，cardiovascular system development， and cell migration. As revealed by KEGG analysis， these proteins were mainly related to peroxisome proliferator-activated receptor （PPAR），focal adhesion，phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt），and Ras-related protein 1 （Rap1） pathways. Western blot results demonstrated that compared with the model group，SGI significantly increased the Plin2 protein expression and decreased the Tpm1 protein expression （P<0.01），consistent with the proteomics results. ConclusionSGI may inhibit cell apoptosis and antagonize H2O2-induced cell oxidative damage by regulating PPAR，focal adhesion，PI3K/Akt and Rap1 pathways，which should be further verified by subsequent experiments.

Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology / 中国中药杂志

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

Analysis and prediction of quality markers of Lonicerae Japonicae Flos / 中国中药杂志

Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.

Study on critical quality attributes of Qingjin Huatan Decoction based on serum pharmacochemistry / 中国中药杂志

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.

Morphology changes of maxillary molar distalization by clear aligner therapy / Cambios de la morfología en la distalización de molares maxilares mediante terapia con alineadores transparentes

SUMMARY: To evaluate the skeletal, dento-alveolar and soft tissue morphology changes after maxillary molar distalization by clear aligner therapy and identify the significant efficacy of molar distalization,18 patients in conformity with the inclusion criteria were selected. Pre- and post-treatment Cone Beam Computed Tomography (CBCT) were examined to measure the angular and linear parameters. All subjects were completed non-extraction clear aligner treatment by distalizing molars. A paired-t test and independent-samples t-test were performed to observe the difference between before and after treatment and the difference between the first molar and second molar respectively. P-values <0.05 were considered statistically significant. Predicted movement rate was calculated by the formula: (actual movement(mm)/planned movement(mm)) x100%. Most variables of pre- and post-treatment showed no statistical difference(P<0.05), excepting SNA angle (P<0.05) and Upper lip/E-line linear (P<0.01) due to incisor retraction. The first and second molar revealed a translation movement without significant tipping and vertical movement. Clear aligners provided a high predictability (83.44 %) of distalization the maxillary first molar, and 85.14 % of the maxillary second molar. Clear aligners can effectively achieve distal displacement of molars.

RESUMEN: Se seleccionaron 18 pacientes, de acuerdo con los criterios de inclusión, para evaluar los cambios en la morfología esquelética, dentoalveolar y de los tejidos blandos después de la distalización de los molares maxilares, mediante la terapia con alineadores transparentes e así identificar la significativa eficacia de la distalización de los molares. Se examinó a través de tomografía computarizada de haz cónico (CBCT) antes y después del tratamiento para medir los parámetros angulares y lineales. Todos los sujetos completaron el tratamiento con alineadores transparentes sin extracción mediante la distalización de los molares. Se realizó una prueba t pareada y una prueba t de muestras independientes para observar la diferencia entre antes y después del tratamiento y la diferencia entre el primer molar y el segundo molar, respectivamente. Los valores de p<0,05 se consideraron estadísticamente significativos. La tasa de movimiento prevista se calculó mediante la fórmula: (movimiento real (mm)/movimiento planificado (mm)) x 100 %. La mayoría de las variables de pre y postratamiento no mostraron diferencia estadística (P<0,05), excepto el ángulo SNA (P<0,05) y el labio superior/línea E lineal (P<0,01) debido a la retracción del incisivo. El primer y segundo molar revelaron un movimiento de traslación sin inclinación significativa y movimiento vertical. Los alineadores transparentes proporcionaron una alta previsibilidad (83,44 %) de la distalización del primer molar superior y del 85,14 % del segundo molar superior. Los alineadores transparentes pueden lograr efectivamente el desplazamiento distal de los molares.

Clinical features of infant cytomegalovirus infection / 中华眼底病杂志

Objective:To observe the ocular clinical features of infantile cytomegalovirus (CMV) infection.Methods:A retrospective clinical study. From March 2019 to July 2021, 876 eyes of 438 children with CMV infection who visited Department of Ophthalmology of Henan Provincial Children's Hospital were included in the study. Among them, there were 254 males and 184 females; the age ranged from 3 days to 11 months; the gestational weeks were 28 to 42 weeks; the birth weight was 1 120 to 8 900 g. There were 384 and 54 full-term and premature infants, respectively. Fundus examination was performed in 385 cases (770 eyes) after medical consultation; 53 cases (106 eyes) of premature infants were routinely screened. CMV retinitis (CMVR) was divided into granular type and fulminant type. Patients with CMV-related diseases with moderate to severe symptoms were given intravenous drip and/or oral ganciclovir; patients with severe fundus vasculitis were combined with intravitreal injection of ganciclovir. The follow-up period was from 4 to 28 months, and the characteristics of eye lesions, systemic comorbid diseases and treatment outcomes were observed.Results:There were 516 eyes of 258 cases with normal fundus (58.9%, 258/438); 291 eyes of 180 cases with CMVR (41.1%, 180/438), of which binocular and monocular were 111 (61.7%, 111/180) and 69 (38.3%, 69/180) cases. Among the 291 eyes of CMVR, 281 eyes (96.6%, 281/291) of granular type; yellow-white point-like opacity and/or retinal hemorrhage; 10 eyes (3.4%, 10/291) of fulminant type; fundus Showed a typical "cheese ketchup-like" and vascular white sheath-like changes. Among the 180 children with CMVR, 72 patients (118 eyes) were given systemic intravenous drip and/or oral ganciclovir; 5 patients (10 eyes) were given intravitreal ganciclovir, all of which were fulminant CMVR. At the last follow-up, fundus lesions regressed significantly in 100 eyes of 61 cases; 18 eyes of 11 cases had old lesions or uneven retinal pigment; 108 cases were not treated.Conclusion:The most common fundus manifestation of CMV infection in infants is granular retinitis, and fulminant retinitis is more severe, and the lesions can be significantly regressed after timely antiviral treatment.

Hyperbaric oxygen therapy can augment the effectiveness of cognition training for persons with vascular cognitive impairment / 中华物理医学与康复杂志

Objective:To explore the effect of combining hyperbaric oxygen (HBO) therapy with cognition training for persons with vascular cognitive impairment (VCI).Methods:Forty-two persons with VCI were randomly divided into a control group of 19 and a research group of 23. In addition to basic treatment, the control group was given hyperbaric oxygen therapy once a day, 5 days per week for 4 weeks, while the research group received cognition training along with the hyperbaric oxygen therapy. Each person′s cognition was assessed using the Simple Mental Status Scale (MMSE) before and after the four-week treatment. Meanwhile, 3ml of venous blood was collected before eating in the morning to test the plasma levels of Klotho protein and homocysteine using enzyme-linked immunosorbent assays.Results:After the treatment the average MMSE score had improved significantly in both group, with the improvement in the research group′s average significantly greater than that in the control group. The average plasma levels of Klotho protein and homocysteine had also improved significantly more in the research group. In the control group, the only significant improvement was in the average homocysteine level.Conclusions:Hyperbaric oxygen therapy can be an effective supplement to cognition training for persons with vascular cognitive impairment.

Effect of etomidate and dexamethasone on cortisol secretion in elderly patients undergoing general anesthesia / 中华麻醉学杂志

Objective:To evaluate the effects of dexamethasone and etomidate on cortisol secretion in elderly patients undergoing general anesthesia.Methods:One hundred and twenty-five elderly patients of either sex, aged 66-90 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, undergoing minor and medium elective surgeries under general anesthesia, were allocated into 4 groups using a random number table method: propofol and normal saline group (group PN, n=31), propofol and etomidate group (group PD, n=31), etomidate and normal saline group (group EN, n=33) and etomidate and dexamethasone group (group ED, n=30). In PN and EN groups, propofol (2 mg/kg) was used to induce and maintain anesthesia, and normal saline 2 ml and dexamethasone 0.1 mg/kg were intravenously injected, respectively, at 5 min before anesthesia induction.In PD and ED groups, etomidate (0.2 mg/kg) was used to induce and maintain anesthesia, and normal saline 2 ml and dexamethasone 0.1 mg/kg were intravenously injected, respectively, at 5 min before anesthesia induction.The serum cortisol concentrations were measured at 8: 00 after entering the operating room on the morning of operation (T 1), 1 h after the start of anesthesia (T 2), 2 h after the start of anesthesia (T 3), 8: 00 on the next day ofoperation (T 4) and 8: 00 on the 2nd day of operation (T 5). Blood glucose concentrations were measured at T 1-T 3, and the hypotension during the peri-anesthesia period, nausea and vomiting in post-anesthesia care unit, and nausea and vomiting scores were recorded at 24 h after operation. Results:A total of 122 patients completed the trial.Compared with PN group, the concentration of serum cortisol was significantly decreased at T 2-T 5, blood glucose concentrations were increased at T 2 and T 3 ( P<0.05), and no significant change was found in the incidence of hypotension, nausea and vomiting and nausea and vomiting scores in PD group ( P>0.05), and the concentration of serum cortisol was significantly decreased at T 2-T 4, the incidence of hypotension was decreased ( P<0.05), and no significant change was found in the blood glucose concentrations, incidence of nausea and vomiting or nausea and vomiting scores in EN group ( P>0.05). Compared with ED group, the serum cortisol concentration was significantly increased at T 2 and T 3, the incidence of hypotension was increased, the incidence of nausea and vomiting and nausea and vomiting scores were decreased ( P<0.05), and no significant change was found in the blood glucose concentrations in PD group ( P>0.05), and the serum cortisol concentration was significantly decreased at T 2 and T 3 and increased at T 4 and T 5, the serum cortisol concentration was decreased at T 2 and T 3, and no significant change was found in the incidence of hypotension, nausea and vomiting and nausea and vomiting scores in EN group ( P>0.05). Conclusions:Combination of etomidate and dexamethasone significantly enhances the duration and degree of inhibition of cortisol secretion in elderly patients than etomidate or dexamethasone alone.

Leptin dysregulated immune responses of B cells in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To explore the effect of leptin on B cells in patients with systemic lupus erythematosus (SLE).Methods:Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients, and then CD19 + B cells were purified with magnetic bead sorting method. PBMCs or purified B cells were cultured with recombinant leptin at 0, 100, 250 ng/ml for 3 or 5 days. The frequencies of plasma cells, follicular helper T (Tfh) cells and peripheral helper T (Tph) cells, as well as activation markers (CD80, CD86) and leptin receptor and the proliferation of B cells were determined with flow cytometry. The concentrations of antibodies and cytokines were examined with enzyme-linked immunosorbnent assay (ELISA). Data were analyzed with t test and analysis of variance (ANOVA). Results:Increased levels of leptin were positively correlated with systematic lupus erythematosus disease activity index (SLEDAI) and the frequency of plasma cells in SLE patients. Leptin receptor could be detected on SLE B cells, and recombinant leptin elevated the levels of its receptor on CD19 + B cells [(7.8±1.3)% vs (6.1±0.9)%, t=3.36, P=0.006]. Leptin enhanced the expression of CD80 [(21±4)% vs (19±4)%, t=2.84, P=0.004] and CD86 [(22±4)% vs (19±4)%, t=4.92, P=0.004] on SLE B cells in vitro. It also promoted B cells to differentiate into plasma cells [(7.6±1.5)% vs (5.2±1.3)%, t=6.42, P=0.025]. There was no statistical significant difference of the effect of leptin on B cell proliferation. Leptin also increased the levels of antibodies [IgG: (62±3) ng/ml vs (45±4) ng/ml, t=7.75, P<0.001; IgM: (112±24) ng/ml vs (56±18) ng/ml, t=5.38, P<0.001] and inflammatory cytokines [IL-6: (24±5) pg/ml vs (20±5) pg/ml, t=4.09, P=0.002; TNF-α: (19.1±3.8) pg/ml vs (14.1±2.9) pg/ml, t=3.38, P=0.006; IL-10: (24±5) pg/ml vs (20±5) pg/ml, t=4.09, P=0.002] secreted by B cells. In addition, leptin significantly upregulated the frequencies of Tfh cells[(2.82±0.49)% vs (1.28±0.20)%, t=4.56, P=0.001] and Tph cells [(4.5±0.5)% vs (3.4±0.4)%, t=3.88, P=0.003]. Conclusion:Leptin could directly promote the activation, differentiation and secretory capacity of B cells by binding to its receptor, and also modulate B cell responses indirectly via enhancement of Tfh and Tph cells, which may be involved in the pathogenesis of SLE.

Pharmacokinetic difference of Shenxiong glucose injection in normal and acute myocardial ischemia rats / 中国药房

OBJECTIVE To compare the phar macokinetics o f ligustrazine hydrochlori de，salvianic acid and rosemarinic acid from Shenxiong glucose injection （SGI）in normal and acute myocardial ischemia （AMI）rats. METHODS Male SD rats were randomly divided into normal group and model group ，with 9 rats in each group. AMI model was established by isoproterenol hydrochloride modeling method. Three rats in each group were selected for model verification. The remaining 6 rats in each group were given SGI （1.2 mL/kg）or equal volum of normal saline via tail vein ；0.3 mL blood was collected through orbital venous bush 0.083，0.167，0.333，0.5，0.75，1，1.5，2，3，5 h after administration. Using luteoloside as internal standard ，the plasma concentrations of ligustrazine hydrochloride ，salvianic acid and rosemarinic acid were determined by ultra performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were fitted by WinNonlin 8.1 software，and statistical analysis was performed by SPSS 18.0 software. RESULTS The linear ranges of ligustrazine hydrochloride ，salvianic acid and rosmarinic acid were 0.06-29.96，0.01-5.15 and 0.006-3.09 μ g/mL（all r＞0.99），respectively. The results of methodological investigation were all in line with the requirements of Chinese Pharmacopoeia （2020 edition）. Compared with normal rats ，CLz of ligustrazine hydrochloride in AMI model rats was significantly increased （P＜0.05）；t1/2 and Vz of salvianic acid were significantly prolonged or increased （P＜0.05）；but the cmax and AUC 0－5 h were significantly decreased （P＜0.05）；AUC0－5 h of rosmarinic acid was significantly decreased （P＜0.05）. CONCLUSIONS The exposure levels of salvianic acid and rosmarinic acid in SGI are lower in AMI model rats than in normal rats ，and the elimination of ligustrazine hydrochloride in AMI model rats is stronger than that in normal rats.

Establishment and comparison of three human multiple myeloma cell line transplantation models in mice / 中华血液学杂志

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.