Cardiovascular complications in malaria: a review / 中国中药杂志

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.

Prevalence and frequencies of human papilloma virus types in adenocarcinoma in situ of the uterine cervix / 中华病理学杂志

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.

Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Effect and Mechanism of Shenlian Formula in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

Effect Analysis of Artemisiae Annuae Herba and Chuanxiong Rhizoma in Treatment of Cerebral Malaria Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio^® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.

Current advances in research on adjuvant therapy for cerebral malaria / 药学学报

Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.

Mechanism of Shengmaiyin (Dangshen Prescription) in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine （ETCM）, and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation，Visualization and Integrated Discovery（DAVID）. Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.

Method for rapid synchronization of different growth cycles of Plasmodium falciparum in vitro and application in differential gene expression profile of 3D7 after dihydroartemisinin treatment / 中国中药杂志

Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P. falciparum and obtain large amounts of parasite with a narrow synchronization window in a short period. Furthermore, the dihydroartemisinin(DHA) was used to treat the early trophozoite phase of P. falciparum 3 D7 for 4 h. Then mRNA was extracted and RNA-seq was conducted to analyze the differential expression of mRNA after drug treatment and obtain the differential gene expression profile. Differential expression of up-regulated genes and down-regulated genes was analyzed according to the screening criteria of |log_2FC|>1 and P<0.05. There, 262 genes were up-regulated and 77 genes were down-regulated. GO functional enrichment analysis of all the differentially expressed genes showed that the enrichment items mainly included cell membrane components, transporter activity, serine/threonine kinase activity, Maurer's clefts(MCs), rhoptry, antigen variation and immune evasion. The enrichment of KEGG pathway included malaria, fatty acid metabolism and peroxisome. Protein-protein interaction(PPI) analysis showed that the down-regulated genes in the modules with high degree of association included rhoptry, myosin complex, transporter and other genes related to the important life activities of malaria invasion and immune escape; the up-regulated genes were mainly related to various toxic exportins of malaria, such as PfSBP1 of MCs. qRT-PCR was used to verify the expression level of some genes, and most of the results were the same as the sequencing results. SBP1 was significantly up-regulated, while some antigenic protein expression levels were down-regulated. Above all, key molecules of DHA therapy were mainly involved in the parasites' rhoptry, transporter, antigenic variation, plasmodium exportin. These results offer us many hints to guide the further studies on mechanism of artemisinin and provide a new way for development of new antimalarial drugs.

Potential therapies for COVID-19 cardiovascular complications using artemisinin and its derivatives intervene based on its cardiovascular protection / 中国中药杂志

Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".

Expert consensus statement on Pudilan Xiaoyan Oral Liquid in clinical practice / 中国中药杂志

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.

Investigation of Skin Irritation of Essential Oils from Interior-warming Medicines / 中国实验方剂学杂志

Objective:To investigate the skin irritation of essential oils(EOs) extracted from interior-warming medicines. Method:Three EOs from interior-warming medicines(Cinnamomi Cortex, Caryophylli Flos and Alpiniae Officinarum Rhizoma) were selected as research objects.The in vitro skin cytotoxicity and in vivo skin irritation of these EOs were determined and compared.Moreover, the skin irritation was also predicted by the novel skin test panels. Result:Toxicity of these three EOs to human skin fibroblasts(HSF) was significantly different, half-inhibitory concentration(IC50) values of EOs from Cinnamomi Cortex, Alpiniae Officinarum Rhizoma and Caryophylli Flos were (11.16±0.28), (53.33±1.71), (226.70±17.61) mg·L-1, respectively.However, in vivo skin irritation evaluation showed that the local toxicity of these three EOs was in the order of EO of Cinnamomi Cortex > EO of Caryophylli Flos > EO of Alpiniae Officinarum Rhizoma. The evaluation results of skin test panels for these three EOs were in accordance with the results of in vivo skin irritation evaluation. Conclusion:Toxicity of these three EOs against skin cells in vitro is inconsistent with their in vivo skin irritation. Skin test panels are expected to be able to accurately predict in vivo skin irritation of EOs instead of cytotoxicity evaluation.

Clinicopathological study of eight cases of atypical placental site nodule / 临床与实验病理学杂志

Purpose To investigate clinical and pathological features,diagnosis and differential diagnosis,treatment and prognosis of the atypical placental site nodules (APSN).Methods 8 cases of APSN were analyzed retrospectively.Their gross and microscopic features and immune phenotypes were observed,and the clinical histories and followed up were also reviewed.Results The patients were 26 to 42 years old (mean 32.8 years old).Clinical symptoms included occupation disease in uterine cavity,irregular vaginal bleeding,etc.Some patients were checked by hysteroscope and showed pale-yellow space-occupying lesions.Microscopically,the lesions consisted of single to multiple nodules or plaques of hyalinized extracelluar matrix,in which chorionic-type intermediate trophoblasts with mild atypia were haphasardly distributed.All the lesions were without myometrial invasion.Chorionic-type intermediate trophoblasts of the 3 cases expressed CK (AEI/AE3),p63,HLA-G,β-catenin,GATA-3 and the Ki-67 labelling index was 8％ ～ 15％.One of the 8 patients had a hysterectomy.Other seven patients were managed by lesionectomy under the hysteroscopy.8 patients were followed up with ultrasonography,curetting endometrium and endocervical mucosa and all of the patients were alive without the progress of the lesion.Conclusion APSN is easily misdiagnosed as squamous cell carcinoma,epithelioid leiomyosarcoma and other gestational trophoblastic diseases.It is important to understand the pathological features of APSN and we can avoid misdiagnosing for other benign or malignant tumours.Misdiagnosis will influence the clinical treatment.

Effect of body mass index on disease-free and overall survival in Chinese women with breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer. The aim of this study was to clarify the effect of obesity on Chinese women with breast cancer.</p><p><b>METHODS</b>This is a retrospective analysis of 1699 breast cancer patients. We evaluated the effect of body mass index (BMI) on disease-free survival (DFS) and overall survival (OS) in these patients. BMI was obtained before surgery. Obesity was defined as a BMI ≥ 24. Kaplan-Meier analysis and Log rank test were employed to perform survival analysis. The impact of different characteristics on survival was assessed by using Cox proportional-hazards regression model.</p><p><b>RESULTS</b>In total 635 (37.4%) patients were obese, while 1 064 (62.6%) were non-obese. Comparing the tumor characteristics in the two groups, the BMI ≥ 24 group showed a higher rate of older age (P < 0.001), postmenopausal status (P < 0.001), increased risk of lymph node metastasis (P = 0.001) and less chances of accepting breast conservation surgery (P = 0.012). The median follow-up time was 16 months, and the estimated 16-months DFS was 98.1% for non-obese and 95.0% for obese patients (P = 0.007), the estimated 16-months OS was 99.4% for non-obese and 98.4% for obese patients (P = 0.004). The multivariate analysis indicated that obesity is an independent prognostic factor for OS and DFS in breast cancer patients.</p><p><b>CONCLUSIONS</b>Our findings suggest that obesity is associated with a poorer outcome in Chinese female patients with breast cancer.</p>

A biodynamic experiment of traditional rolling massage and its experimental device development / 中国组织工程研究

BACKGROUND:Methods after mechanical stimulation can be combined with various kinds of cells to produce many conversion types so as to start the various physiological functions of the body. OBJECTIVE:To analysis the reason why rol ing massage can improve the intracellular concentration of Ca2+METHODS:A biodynamic experimental device was set up, composed of pressure generating device, pressure forming device, pressure display device and related data recording device. We detected the effects of rol ing massage on Ca . 2+concentration in normal skeletal muscle cells and damaged cells through the different functions of the experimental device and system software. These functions consisted of pressure display, data transmission and recording, signal acquisition and processing, pressure signal acquisition, control and processing of signal acquisition, wireless signal transmission and receiving system, display system, storage system, system implementation function. RESULTS AND CONCLUSION:The experiment results showed that rol ing massage could reduce the Ca 2+concentration in the normal skeletal muscle cells and damaged cells. These findings suggest that rol ing massage can improve the overload of intracellular Ca2+in damaged cells, and it is superior to the sinusoidal mechanical stimulus.

Effect of DC-CIK cell on the proliferation, apoptosis and differentiation of leukemia cells

OBJECTIVE@#To observe the effect of co-culture cytokine-induced killer cells (CIK) and homologous dendritic cells (DC) on the proliferative activity and phenotype change of the DC-CIK cell and the cell killing activity of leukemia HL-60.@*METHODS@#50 mL cord blood sample was obtained from infants delivered by full term healthy woman and the cord blood mononuclear cells were isolated by density gradient centrifugation. Non-adherent cells were collectedfor the induction culture of CIK, adherent cells were differentiated into mature DC; cultured mature DC was mixed with and CIK in the proportion of 1:5 for 12 d. Killing activity of DC-CIK co-cultured cell on leukemia HL-60 was detected by MTT assay.@*RESULTS@#Compared with CIKs, the co-cultured DC-CIKs presented a markedly higher proliferation and killing activity.@*CONCLUSIONS@#Co-culture of DC-CIK cells led to a significant increase of the proliferation and cytotoxicity of CIK.

Transplantation of human neural precursor cells in the treatment of children with pervasive developmental disorder / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.</p><p><b>METHODS</b>Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later.</p><p><b>RESULTS</b>No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05).</p><p><b>CONCLUSIONS</b>These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.</p>

Clinical effect of stem cell transplantation via hepatic artery in the treatment of type II hyperammonemia: a report on 6 cases / 中国当代儿科杂志

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.

Treatment of cerebral palsy with transplantation of human neural progenitor cells / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children.</p><p><b>METHODS</b>Forty-five children with CP were voluntarily accepted transplantation of hNPCs. The cells obtained from the forebrain of 10 to 12-week-fetus were cultured and amplified into hNPCs. Then the hNPCs were injected into the cerebral ventricle of the patients with the supersonic guidance.</p><p><b>RESULTS</b>Dyssomnia, irritability and muscular tension were improved in one patient 3 days after transplantation. The clinical improvements were observed in the majority of the patients 1 month after transplantation. The therapeutic effects slowed down 3 to 6 months after transplantation. One year after transplantation the gross and fine motor skills and the congnition ability in the transplantation group were considerably surpassed to those in the control group. No delayed severe complications were observed after transplantation. No tumorigenesis was noted 5 years after transplantation.</p><p><b>CONCLUSIONS</b>The transplantation of hNPCs as a novel therapy is effective and safe for severe CP. Many investigations are needed to evaluate the effect of the therapy.</p>

Comparison of stability of sacroiliac screws in the treatment of bilateral sacral fractures in a finite element model / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the stability of sacroiliac screws fixation for the treatment of bilateral vertical sacral fractures to provide reference for clinic application.</p><p><b>METHODS</b>A finite element model of Tile C pelvic ring injury (bilateral type Denis II fracture of sacrum) was produced. The bilateral sacral fractures were fixed with sacroiliac screws in 4 types of models respectively: two bidirectional sacroiliac screws fixation in the S₁ segment, two bidirectional sacroiliac screws fixation in the S₂ segment, one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment, two bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively. By the ABAQUS 6.9.1 software, in the case of standing on both feet, 600 N vertical load was imitated to be imposed to the superior surface of the sacrum and downward translation and backward angle displacement of the middle part of the sacral superior surface and everted angle displacement of the top of iliac bones were extracted for analysis. The stability of sacroiliac screws fixation was compared according to the principle of the better stability the smaller displacement.</p><p><b>RESULTS</b>The stability of 2 bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively was markedly superior to that of 2 bidirectional sacroiliac screws fixation in S₁ or S₂ segment and was also markedly superior to that of one sacroiliac screw fixation in S₁ segment and one sacroiliac screw fixation in S₂ segment. The vertical and everted stability (the downward translation: 0.531 mm; the everted angle displacement: 0.156° (left side), 0.163° (right side)) of sacroiliac screws fixation in two bidirectional sacroiliac screws fixation in the S₂ segment was superior to that of two bidirectional sacroiliac screws fixation in the S₁ segment (the downward translation: 0.673 mm; the everted angle displacement: 0.200° (left side), 0.232° (right side)). The rotational stability of two bidirectional sacroiliac screws fixation in the S₁ segment (the backward angle displacement: 0.269°) was superior to that of two bidirectional sacroiliac screws fixation in the S₂ segment (the backward angle displacement: 0.287°). Moreover, the rotational stability of one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment was inferior to that of two bidirectional sacroiliac screws fixation in the S₁ segment or two bidirectional sacroiliac screws fixation in the S₂ segment, and the vertical and everted stability of one sacroiliac screw fixation in the S₁ segment and one sacroiliac screw fixation in the S₂ segment was between that of two bidirectional sacroiliac screws fixation in the S₁ segment and two bidirectional sacroiliac screws fixation in the S₂ segment.</p><p><b>CONCLUSIONS</b>Two bidirectional sacroiliac screws fixation in S₁ and S₂ segments respectively is recommended to be utilized for fixing bilateral sacral fractures of Tile C pelvic ring injury as far as possible. It is suggested to choose sacral segments in which sacroiliac screws fixed according to vertical, rotational and everted stability degree of sacral fractures.</p>

Involvement of intron A into eukaryotic expression vector to improve immunogenicity of mycobacterial heat-shock protein 65 DNA vaccine in mice / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the involvement of intron A into eukaryotic expression vector to improve antigen expression efficiency and enhance immunogenicity of DNA vaccine in mice.</p><p><b>METHODS</b>As model antigen, the coding gene of mycobacterial Hsp65 was cloned into eukaryotic expression vector pCMV4.0 with intron A involved and pVAX1 without intron A involved, respectively. The resulted recombinant expression vectors were transfected into 293T cells and were then injected into BALB/c mice as DNA vaccines. Anti-Hsp65 specific IgG and isotype were detected by ELISA and T cell immune response was analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay and intracellular cytokine staining.</p><p><b>RESULTS</b>Compared with non-intron A pVAX1hsp65, the recombinant plasmid pCMV4.0hsp65 involved with intron A pVAX1hsp65 caused higher expression level of Hsp65 in 293T cells, and enhanced Th1 type immune response, which was defined as higher level of anti-Hsp65 specific total IgG level (3.76 ± 0.23 vs 3.15 ± 0.22, P < 0.01) and IgG2a/IgG1 ratio (4.08 ± 0.04 vs 2.23 ± 0.12, P < 0.01) and more IFN-γ-secreting CD4(+) ((2.0 ± 0.058)% vs (1.5 ± 0.087)%, t = 4.804, P < 0.01) and CD8(+) ((0.6 ± 0.058)% vs (1.0 ± 0.115)%, t = 3.098, P < 0.05) T lymphocytes. The difference showed statistical significance.</p><p><b>CONCLUSION</b>Intron A can improve the expression efficiency of mycobacterial Hsp65 antigen and enhance immunogenicity of DNA vaccine in mice when involved into eukaryotic expression vector.</p>