Analysis of ocular clinical features in 13 children with methylmalonic acidemia / 中华眼底病杂志

Objective:To observe the clinical features of eyes in children with methylmalonic acidemia (MMA).Methods:A retrospective clinical case study. From June 2019 to June 2022, 13 children with MMA visited on the Department of Ophthalmology of Henan Children's Hospital were included in the study. The anterior segment and fundus were examined under surface or general anesthesia. Best corrected visual acuity (BCVA) and refraction were performed in 9 cases; fluorescein fundus angiography (FFA) was performed in 3 cases; flash electroretinogram (FERG) was performed in 6 cases; flash visual evoked potential (FVEP) was detected in 6 cases; optical coherence tomography (OCT) was performed in 3 cases.Results:Among the 13 pediatric patients with methylmalonic acidemia, 6 cases were male and 7 cases were female. The average age at first visit was 45 months. All cases suffered from hyperhomocysteinemia; 9 cases were with epilepsy; 2 cases were with infantile spasms; 11 cases were with stunting, 13 cases were with repeated pulmonary infection during growth period; 4 cases were with hydrocephalus; 1 cases was with hypertension and renal insufficiency. Genetic dectection results of 8 cases were recorded, MMACHC:c.609G>A:p.W203* mutation site was found in all cases. One case was accompanied by corneal ulcer. There were 10 cases with nystagmus, 4 cases with macular degeneration, 3 cases with hyperopic refractive error and esotropia. Nine cases underwent BCVA examination, BCVA was light perception-0.6. In OCT, 2 cases of 3 cases showed retinal thinning and photoreceptor cell layer atrophy in the macular area. In FFA, 2 cases of 3 cases showed circular transparent fluorescence in the macular area. Five cases of 6 cases who with FVEP had different degrees of P100 peak time delay and decreased amplitude, and 4 cases of 6 cases with FERG had decrease of a and b wave in light and dark adaptation. Conclusions:The clinical phenotypes of eyes in children with MMA are various and the severity was different; most of them are accompanied by nystagmus, and the fundus lesions are common in the characteristic bovine eye like macular region. Those with macular disease have severe visual impairment.

Research status of psychosocial effects and interventions in cancer anorexia/cachexia syndrome patients / 中国实用护理杂志

Cancer anorexia/cachexia syndrome (cancer anorexia cachexia syndrome, CACS) is a common complication in advanced cancer patients, which is characterized by reduced feeding, sustained weight loss, general fatigue and weakness. CACS related symptoms make patients suffer from a series of adverse psychosocial effects, such as anxiety, pain and social isolation, thus bringing serious adverse effects on patients′ individuals, families and society. This paper reviewed the symptoms associated with CACS and their psychosocial effects, as well as the interventions related to adverse psychosocial effects, in order to provide theoretical reference for alleviating psychosocial distress and improving health-related quality of life of patients with CACS.

Analysis of Chemical Components of Anti-allergic Asthma Active Fractions in Alkaloids-free Part of Ephedrae Herba / 中国药房

OBJECTIVE：To provide reference for elucidating the anti-allergic asthma constituents in alkaloids-free part of Ephedrae Herba. METHODS ：Ephedrae Herba was extracted with 85％ ethanol and n-heptane，and then subjected to solid-phase extraction（filler AC 18）for pretreatment to enrich alkaloids-free part from the extract of Ephedrae Herba. HPLC method was adopted，and alkaloids-free fractions of Ephedrae Herba were performed on Unitary C 18 column and Eclipse XDB-C 18 column. Using high expression G protein coupled-receptor 35（GPR35 receptor）in HT- 29 cell as target ，GPR35 receptor agonist zaprinast （1 μmol/L）as positive control ，DMR response value as the detection index ，the agonistic and desensitizing activity of each fraction（100 μg/mL）on GPR 35 receptor was screened by label-free integrated pharmacological method ，so as to screen active anti-allergic asthma fraction. HPLC-Q-TOF-MS method was used to identify the chemical composition of the selected active fractions. RESULTS ：The alkaloids-free part of Ephedrae Herba was divided into two parts ，involving the precipitated part before solid phase extraction and the 95％ methanol elution part ；from them ，20 fractions were screened. Among them ，the precipitated fraction F 1.5-F1.10 and 95％ methanol eluted fraction F 2.5-F2.10 had a strong agonistic activity on GPR 35 receptor；at the same time，GPR35 receptor agonist zaprinast showed a relatively strong desensitization activity. The signal intensity of DMR induced by F1.5-F1.10 in the precipitated part of HT- 29 cells was even higher than that of reference drug zaprinast. By HPLC-Q-TOF-MS analysis，24 chemical components were identified from active fractions ，involving 14 flavonoids，2 volatile oils ，7 organic carboxylic acids ，1 anthraquinones. CONCLUSIONS ：The alkaloid-free part of Ephedrae Herba is mainly flavonoids and has anti-allergic asthma activity.

Follow up of observation in patients with retinoblastoma under special circumstances / 中华眼底病杂志

Objective:To observe the retinoblastoma (RB) reexamination of children with new and recurrence retinoblastoma under special circumstances.Methods:From January 2, 2020 to March 15, 2020, 30 children with RB who had fundus examination in Henan Children's Hospital were enrolled in this study. Among them, 14 were male, 16 were female; 18 were monocular and 12 were binocular. The average age was 37.07±18.15 months. The mean age of initial diagnosis was 20.23±13.77 months. Two patients had a family history (6.67%). In 42 eyes, stage B, C, D and E were 7, 8, 20 and 7 eyes, respectively. Twenty-one eyes had finished the treatment course and 21 eyes were during treatment. All the children underwent RetCam fundus examination, orbital MRI, ocular B-ultrasound and so on. Whether the children had new tumor or recurrence at different treatment stages was observed.Results:Among 7 eyes in stage B, there was no recurrence or new tumor at the end of treatment or in the process of treatment. Among 8 eyes in stage C, there were 1 eye with new tumor and 1 eye with activity tumor at the end of treatment. Among 20 eyes in stage D, there were 1 eye with recurrence tumor at the end of treatment, 3 eyes with new tumor and 7 eyes with activity tumor at the end of treatment. Among 7 eyes in stage E, 5 eyes had eyeball enucleation and 2 eyes were receiving treatment; there were 1 eye with activity tumor at the end of treatment, 1 eye with recurrence tumor, 1 eye with activity tumor. Among 18 monocular eyes, there were 11 eyes in the treatment process, 2 eyes with new tumor, 1 eye with recurrence tumor and 3 eyes with activity tumor. Of the 24 binocular eyes, 10 were receiving treatment and there were 3 eyes with new tumor, 6 eyes with activity tumor. Twenty-one eyes had finished the treatment course, the average time required for follow-up was 3.71±0.31 months, and the average time delayed for follow-up was 6.43±1.66 weeks. There was a recurrence of tumor in 1 patient who had finished the whole treatment, the incidence was 4.76%. In the course of treatment, 21 eyes were required to have a follow-up time of 3 weeks, and the average delayed follow-up time was 6.00 ± 1.89 weeks. There were 5 eyes with new tumors, with a incidence of 21.74%. Nine eyes still had activity and needed to be treated in time.Conclusions:The higher the risk of tumor staging, the more relapses and new tumors. The patients who are being treated, the time of delayed follow-up, the higher the recurrence or new tumor than the children who have finished the treatment course and delayed the follow-up. The children who have relapsed or new tumor in the treatment course of binocular are higher than the children who have monocular.

Study on Homology Modeling of eEF 2K Protein and Virtual Screening of Its Inhibitors Molecules / 中国药房

OBJECTIVE： To screen potential eEF2K inhibitor molecules， and to provide reference for the design and R&D of eEF2K inhibitor. METHODS： The eEF2K crystal structure model was constructed by homology modeling technique. The model was optimized by Loop optimization and molecular dynamics. With the help of SAVES online server， the above models were evaluated from three aspects such as Verify_3D， EERAT and Laplace diagram. Totally 55 eEF2K inhibitor molecules were collected. Hypogen pharmacophore model with activity prediction ability was constructed based on 28 of them （odd number， as training set） by Insight Ⅱ software and validated by other 27 （even number， as test set）. The optimal pharmacophore model was screened by fitting the predicted and experimental values of activity [i.e. negative logarithm of half inhibitory concentration （pIC50）] and using Ligand profiler thermogram. The virtual screening of small molecules of eEF2K inhibitors was carried out by combining the above pharmacophore model， Lipinski’s five rules and molecular docking method. RESULTS & CONCLUSIONS： The overall quality factor score of the crystal structure model of eEF2K protein was 93.697. Among them， 83.33％ of the amino acid Verify_3D score was more than or equal to 0.2， and 1.7％ of the total amino acids were located in the non-permissible region. The amino acid conformation and skeleton structure of the model were reasonable and the reliability of the model was high. Totally 9 Hypogen pharmacophore models （No. 02-10） with active predictive function were constructed， among which No. 03 pharmacophore model included 2 hydrogen bond receptors and 2 conjugated aromatic rings， which could better distinguish active and inactive molecules. The predicted value of pIC50 fitted the experimental value best （the correlation coefficient was 0.665 3）， and it had good predictive ability and high reliability. Finally， 9 potential eEF2K inhibitor molecules were obtained through virtual screening （pIC50 ranged from 1.074 to 1.185， and Dcoking-score of protein-molecule interaction ranged from －9.730 to －7.467）. Pro268， Asp267， Gln171， Phe121 and Glu212 may be the key amino acids for the interaction between eEF2K inhibitors and target proteins， including hydrogen bonds， salt bridges and hydrophobicity. These 9 molecules are expected to be the lead compounds for the development of eEF2K inhibitors.

Simultaneous Determination of Contents of Asiaticoside, Tetrahydropulmatine and Saikosaponin d in Shenji Huwei Granules by HPLC / 中国中医药信息杂志

Objective To develop an HPLC method for simultaneous determination of contents of asiaticoside, tetrahydropulmatine and saikosaponin d in Shenji Huwei Granules. Methods The analysis was performed on a R&C C18 column (250 mm × 4.6 mm, 5 μm) by using the mobile phase of acetonitrile (A) - phosphate buffer (which used potassium dihydrogen phosphate 8.34 g, potassium phosphate 0.87 g dissolved by 1000 mL water) with gradient elution (0–15 min, 20％A; 15–30 min, 20％→40％A; 30–42 min, 40％A; 42–45 min, 40％→48％A; 45–50 min, 48％A; 50–70 min, 48％→50％A). The flow rate was 1.0 mL/min; the detection wavelength was set at 210 nm; the column temperature was maintained at 30 ℃. Results Asiaticoside, tetrahydropulmatine and saikosaponin d were in the linear ranges among 0.173–2.770 μg (r=0.9999), 0.021–1.320 μg (r=0.9992), 0.151–9.660 μg (r=0.9993), respectively. The average recovery rates of asiaticoside, tetrahydropulmatine, saikosaponin d were 96.25％, 97.02％, and 97.84％, respectively, and RSD were 2.31％, 4.51％, 1.87％, respectively. Conclusion This method is simple, with good separation effect and strong specificity, and can be used for simultaneous determination of contents of asiaticoside, tetrahydropulmatine and saikosaponin d in Shenji Huwei Granules, which provides references for perfection of quality control of Shenji Huwei Granules.

Research Progress in Bioavailability Improvement Methods for Curcumin / 中国药师

Curcumin is the main active component in turmeric, which possesses many pharmacologic effects, including anti-in-flammatory, antioxidant, anti-tumor, anti-atherosclerosis, liver and kidney protection and so on. However, due to its poor bioavail-ability, its clinical application is limited. Therefore, the methods for improving the bioavailability of curcumin were reviewed by refer-ring to a large number of literatures. The bioavailability of curcumin can be improved by different administration routes and various dos-age forms. The review provides theoretical basis and research ideas for the development of new drugs.

Research Progress in Absorption Evaluation Methods for Pulmonary Delivery / 中国药师

Objective:To review the drug absorption evaluation methods for pulmonary delivery. Methods: The drug absorption cell models, in vitro pulmonary membrane model and in vivo animal model were systematically summarized, and the advantages and disadvantages of those models and applications were reviewed by referring to the databases in CNKI and Pubmed. Results:The appro-priate animal model and method for the study of pulmonary absorption should be chosen according to the experimental purpose and char-acteristics of drugs. Conclusion:The review provides the thoughts and theoretical basis for the research and development of pulmonary delivery.

Study on Preparation and Application of Surface Molecularly Imprinted Polymer Based on Mesopocous Molecular Sieve SBA-15 / 中国药房

OBJECTIVE:To prepare mesopocous molecular sieve SBA-15 surface molecularly imprinted polymer (SBA-15@MIP),and analyze the application of SBA-15@MIP in the determination of active micro-component. METHODS:Using baica-lein as the template molecule,acrylamide(AM)as the function monomer,tetrahydrofuran/ethanol(3∶2,V/V)as the polymeriza-tion solvent,ethylene glycol dimethacrylate(EGDMA)as the cross-linker,and 2,2-azobisisobutyronitrile(AIBN)as the initiator, SBA-15@MIP was synthesized on the surface of mesopocous molecular sieve SBA-15. The surface morphology and structure of the obtained polymer were characterized by TEM and FT-IR. Finally,the imprinted polymer was used as an adsorbent for solid-phase extraction (SPE) to detect baicalein in plasma samples by HPLC. RESULTS:It revealed that the well-ordered one-dimensional pore structure of SBA-15 was still preserved in the successful synthesized SBA-15@MIP,and baicalein molecule was imprinted suc-cessfully. The limit of detection(LOD)and limit of quantification(LOQ)for baicalein in plasma were 3.5 ng/ml and 11.6 ng/ml, respectively;the average recovery was 94.4%(RSD=2.9%). CONCLUSIONS:SBA-15@MIP is prepared successfully,and can be applied for the determination of active micro-component.

Study on Purpurin As A G Protein-coupled Receptor-35 Agonist / 世界科学技术-中医药现代化

Purpurin is a common component ofRubia cordifolia L. The study on its molecular target was useful for elucidating the therapeutic material basis and action mechanism ofR. cordifolia. HT-29 cells were used in the cell culture. The highly expressed G Protein-coupled Receptor-35 (GPR35) agonist was used as target. The label-free optical biosensor cellular assay was used to investigate the agonist activity ofpurpurin at an endogenous receptor. The results showed thatpurpurin can cause DMR response in HT-29 cells. And the DMR response curve type was consistent with zaprinast. Its EC50 was 6.142± 0.189μmol·L-1. In addition,purpurinhad desensitization effect on GPR35 agonist zaprinast in HT-29 cells. GPR35 agonist ML145 blocked the DMR ofpurpurin. It was concluded thatpurpurinwas the GPR35 agonist.

Anti-tumor effect of Sendai virus Tianjin strain defective interfering particles on tumor-bearing mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the anti-tumor effect and its mechanism of Sendai virus Tianjin strain defective interfering particles (DIP) on mouse models of colon carcinoma.</p><p><b>METHODS</b>CT26 cells (5×10(6)/0.1 ml) were subcutaneously injected into the back of Bal B/c mice to establish murine colon carcinoma model. After the tumors reached 5 mm in diameter, the mice were randomly divided into Tianjin strain DIP group and saline control group. The former was intratumorally injected with Tianjin strain DIP (0.1 ml) once a day on day 4, 7, 10 and 13 after CT26 cell inoculation. The latter was intratumorally injected with the same volume of saline. Tumor volume and survival rate of the mice were calculated to confirm the anti-tumor effect of DIP. Flow cytometry and ELISA were used to examine the maturation and release of cytokines IL-6, IFN-α and TNF-α from murine myeloid dendritic cells (DCs) induced by Tianjin strain DIP. Moreover, real-time RT-PCR and immunohistochemistry were performed to identify whether the Tianjin strain DIP could induce infiltration of CD11c(+) DCs, CD4(+) and CD8(+) T cells in the tumors.</p><p><b>RESULTS</b>On day 22 after CT26 cell inoculation, the average tumor volume of the Tianjin strain DIP group was (33.2 ± 2.0) mm(3), significantly smaller than that of the control group [(2 376.0 ± 130.8)mm(3), P < 0.01]. On day 50 after CT26 cell inoculation, the survival rate of mice was 90.0% in the Tianjin strain DIP group, much higher than that of the control group (30.0%, P < 0.01). Flow cytometry analysis showed that the expression of markers of DCs maturation, including CD40, CD80 and CD86, was dose-dependently increased by DIP or intact virus. No statistically significant difference was found betweent the DIP and intact virus groups. ELISA results showed that DIP could stimulate the secretion of IL-6, IFN-α and TNF-α from mouse DCs. The secretion of all of the cytokines was dose-dependently increased by DIP or intact virus. Real-time RT-PCR revealed that the expression of CD4, CD8 and CD11c mRNAs was increased in tumors treated with DIP compared with that of the saline group at all time points. Moreover, the expression level of all of them remained maximal at 120 h after the last treatment. Immunohistochemical staining revealed that the ratios of CD4(+), CD8(+) T cells or CD11c(+) DCs to total cells were (21.60 ± 1.49)%, (22.12 ± 2.84)% and (23.05 ± 2.91)%, respectively, in the DIP-treated tumors. In the tumors treated by saline, the ratios were (2.62 ± 0.60)%, (4.05 ± 0.12)% and (3.10 ± 0.09)%, respectively. The difference between experimental group and control group had statistical significance.</p><p><b>CONCLUSIONS</b>Tianjin strain DIP may exert anti-tumor effect on tumor-bearing mice. The mechanism is related with the antitumor immunity induced by DCs and T cells.</p>

Study on the apoptosis of rat glioma cells induced by defective interfering particles of Sendai virus strain Tianjin / 中华微生物学和免疫学杂志

Objective To investigate the apoptosis of rat glioma C 6 cells induced by defective in-terfering( DI) particles of Sendai virus strain Tianjin .Methods Rat glioma C6 cells were treated with dif-ferent titers of DI particles of Sendai virus strain Tianjin in vitro with culture media as negative control and intact virus as positive control .At different time point , cells were collected and their apoptosis was detected by DNA gel electrophorsis , TUNEL assay and AnnexinⅤ/PI double-labeled flow cytometry .The C6 glioma-bearing rat model was established and then treated with three intratumoral injections of DI particles , intact virus or saline three times at interval of two days .The antitumor effects of ID particles were evaluated through daily measuring of the tumor size .Hematoxylin-eosin( HE) staining was used to observe the patho-logical changes in tumor tissues .TUNEL assay was performed to detect the apoptosis of tumor tissues .Re-sults Rat glioma C6 cells treated with DI particles or intact virus in vitro showed typical DNA ladder pattern in agarose gel electrophoresis in a time-and dose-dependent manner .With the intervention of DI particles , the apoptosis rate of C6 cells showed a time-and dose-dependent manner and was significantly higher than that of the control group (P0.05).Conclusion The DI particles of Sendai virus strain Tianjin could induce apoptosis of rat glioma C 6 cells in a time-and dose-dependent manner both in vitro and in vivo, suggesting that the DI particles might be applicable for the treatment of neurogliocytoma in the future.

Individualized partial laryngectomy during surgery of epiglottic carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate an individualized operative modality of partial laryngectomy for suprahyoid epiglottis centered epiglottic carcinoma.@*METHOD@#Eleven cases of epiglottic squamous carcinoma which primarily focused in the suprahyoid region were included. Preoperative CT indicated that obvious margin with low density existed in the pre-epiglottic space in 3 cases, and pre-epiglottic space were involved in 8 cases, among which the arytenoid region were involved in 2 cases. An individualized partial laryngectomy was manipulated beyond the safe margin, an arytenoid epiglottic fold-plasty was performed and the remaining epiglottis was fixed to the tongue base. Adjuvant postoperative radiotherapy and chemotherapy were applied to all patients and the follow-up time lasted from 1 to 6 years with mean time of 3 years and 6 months.@*RESULT@#One patient died of recurrence in the tongue base after one year postoperatively, one was lost to follow-up 2 years after surgery. The overall 3-year survival rate was 81.8%. Nine patients were free from tracheal cannulation within one year postoperatively and the other two patients went on with tracheal tube assisted respiration. Aspiration gradually disappeared within 1-3 months.@*CONCLUSION@#Individualized partial laryngectomy in treatment of epiglottic carcinoma could preserve more laryngeal tissue and result in better laryngeal function preservation.

Bioinformatic Analysis of Structural Proteins of Paramyxovirus Tianjin Strain / 中国病毒学·英文版

The amino acid sequences of the NP,P, M, F,HN and L proteins of the paramyxovirus Tianjin strain were analyzed by using the bioinformatics methods. Phylogenetic analysis based on 6 structural proteins among the Tianjin strain and 25 paramyxoviruses showed that the Tianjin strain belonged to the genus Respirovirus, in the subfamily Paramyxovirinae, and was most closely related to Sendal virus (SeV). Phylogenetic analysis with 14 known SeVs showed that Tianjin strain represented a new evolutionary lineage. Similarities comparisons indicated that Tianjin strain P protein was poorly conserved, sharing only 78.7%-91.9% amino acid identity with the known SeVs, while the L protein was the most conserved, having 96.0%-98.0% amino acid identity with the known SeVs. Alignments of amino acid sequences of 6 structural proteins clearly showed that Tianjin strain possessed many unique amino acid substitutions in their protein sequences, 15 in NP, 29 in P, 6 in M, 13 in F, 18 in HN, and 29 in L. These results revealed that Tianjin strain was most likely a new genotype of SeV. The presence of unique amino acid substitutions suggests that Tianjin strain maybe has a significant difference in biological, pathological, immunological, or epidemiological characteristics from the known SeVs.

Antigenicity and Hemaglutination Activity of a Recombinant Hemagglutinin-Neuraminidase of Paramyxovirus Tianjin Strain / 中国病毒学·英文版

Paramyxovirus Tianjin strain, a new genotype of Sendal virus, was isolated from the lungs of common cotton-eared marmoset that died of severe respiratory infection in the marmoset colonies. The 19.28% IgM positive rate in the young children with acute respiratory tract infection suggested a close relationship between Tianjin strain and humans. Hemagglutinin-neuraminidase (HN) is its major transmembrane glycoprotein responsible for viral attachment, penetration and release. To clear the relationship between HN structure and function of paramyxovirus Tianjin strain, rHN1, rHN2 and rHN3 overlapping the ectodomain of HN protein were expressed. Their antigenicity and hemaglutination activity, as well as cross reactivity to standard antisera against influenza virus type A, type B were analyzed. The results indicated expressed rHNs have the natural antigenicity.The segment rHN2 possesses more linear epitopes exposed on the surface of the native I-IN protein than found in segments rHN3 and rHN1. The hemagglutination activity of segment rHN3 is higher than that of segments rHN2 and rHN1, and partially dependent on the three-dimensional conformation of HN3 protein. Cross-reactivity between rHNs and standard antisera against influenza virus type A, type B suggested that rHNs might not be the best alternative as specific antigens to detect virus in clinicalserum specimens.