Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Clinical and genetic analyses of Joubert syndrome in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and genetic features of Joubert syndrome (JS) in children.@*METHODS@#A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022.@*RESULTS@#Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes.@*CONCLUSIONS@#For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

Improving the activity of creatinase from Alcaligenes sp. KS-85 through semi-rational design / 生物工程学报

Creatinine levels in biological fluids are important indicators for the clinical evaluation of renal function. Creatinase (CRE, EC3.5.3.3) is one of the key enzymes in the enzymatic measurement of creatinine concentration, and it is also the rate-limiting enzyme in the whole enzymatic cascade system. The poor catalytic activity of CRE severely limits its clinical and industrial applications. To address this issue, a semi-rational design is applied to increase the activity of a creatinase from Alcaligenes sp. KS-85 (Al-CRE). By high-throughput screen of saturation mutagenesis libraries on the selected hotspot mutations, multiple variant enzymes with increased activity are obtained. The five-point best variant enzyme (I304L/F395V/K351V/Y63S/Q88A) were further obtained by recombine the improved mutations sites that to showed a 2.18-fold increased specific activity. Additionally, structure analysis is conducted to understand the mechanism of the activity change. This study paves the way for a better practical application of creatinase and may help further understand its catalytic mechanism.

Time to initial diagnosis of imported malaria and its influencing factors in Jiangsu Province / 中国血吸虫病防治杂志

Objective To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. Methods The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. Results A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. Conclusions Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.

Research progress on rutin derivatives / 中国中药杂志

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

High tibial osteotomy combined with lateral retinacular release for the treatment of knee varus osteoarthritis with lateral patellar compression syndrome / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of high tibial osteotomy combined with arthroscopic lateral retinacular release in the treatment of knee varus osteoarthritis.@*METHODS@#From October 2017 to April 2019, a retrospective analysis was performed on 43 patients with knee varus osteoarthritis and lateral patellar compression syndrome treated by high tibial osteotomy combined with arthroscopic lateral retinacular release. There were 15 males and 28 females, aged 53 to 72(62.05±5.17) years. The visual analogue scale(VAS), Lysholm, and the knee range of motion were used to evaluate knee pain and functional recovery before operation, 2 weeks, 3 months and 12 months after operation. And the congruence angle (CA), patellar tilt angle (PTA), and femala-tibial angle (FTA) were measured respectively before and 12 months after operation to evaluate the congruence of patellar joint, and the improvement of line of gravity of lower limb.@*RESULTS@#All 43 patients were followed up for more than 12 months, with a follow-up time of 14 to 28 (19.60±4.50) months. The VAS scores decreased from 6.65±0.65 before operation to 2.16±0.95, 0.51±0.77 and 0.33±0.64 at 2 weeks, 3 months and 12 months after operation, and the difference was statistically significant (@*CONCLUSION@#High tibial osteotomy combined with arthroscopic lateral retinacular release can relieve weight-bearing pain in frontal axis and improve the function of knee in sagittal axis.

Identification of Chinese medicine sea snake based on cytochrome B (Cytb) / 中国中药杂志

The identification of species primordium has been one of the hot issues in the identification of traditional Chinese medicine. Sea snake is one of the most valuable Chinese medicinal materials in China. In order to understand the origin and varieties of sea snake in the market, we studied the molecular identification of 46 sea snakes by cytochrome B(Cytb). After comparison and manual correction, the sequence length was 582 bp, and the content of A+T(58.9%) was higher than that of G+C(41.1%). There exist 197 variable sites and 179 parsimony-informative sites of the sequence. There are 44 kinds of sequence alignment with consistency equal to 100%, and 2 kinds equal to 96%. A total of 408 Cytb effective sequences were downloaded from GenBank database, with a total of 68 species. Phylogenetic tree of a total of 454 sea snake sequences with the samples in this study were constructed by neighbor-joining trees and Bayesian inference method, respectively, which can identify 42 samples of medicinal materials, while 4 samples can not be identified because of their low node support. The results showed that the species of the sea snake medicine were at least from 2 genera and 5 species, namely, Aipysurus eydouxii, Hydrophis curtus, H. caerulescen, H. curtus, H. ornatus and H. spiralis. This study suggested that the original species of commercial sea snake are very complex and can provide insight into the identification of sea snakes.

Effect of rehabilitation treatment based on the ICF-CY Core Sets on activities of daily living in children with cerebral palsy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVE@#To study the effect of rehabilitation treatment based on the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) Core Sets on activities of daily living in children with cerebral palsy.@*METHODS@#The children with cerebral palsy were divided into an observation group (@*RESULTS@#There was no significant difference in the scores of the WeeFIM and Social-Life Abilities scales between the two groups before treatment (@*CONCLUSIONS@#The rehabilitation treatment regimen for cerebral palsy based on the CF-CY Core Sets pays more attention to the influence of environmental factors in the process of rehabilitation and can effectively improve the activities of daily living of children with cerebral palsy.

Role of Chinese Medicine in Regulation of Epilepsy-related Signaling Pathways： A Review / 中国实验方剂学杂志

Epilepsy is a common nervous system disorder characterized by repeated attacks and a protracted course， which can cause great harms to the physical and mental health of patients. Antiepileptic drugs have been proved effective， but the resulting toxic and side effects cannot be ignored. Traditional Chinese medicine （TCM） has a long history of dealing with epilepsy. At present， in addition to enriching the cognitive theory of epilepsy treatment with TCM， we have also focused on the role of TCM in regulating the epilepsy-related signaling pathways from the perspective of molecular biology. The review of literature in China and abroad has uncovered that epilepsy is closely related to such pathophysiological processes as cell proliferation， apoptosis， autophagy， inflammatory response， and immune response. At the same time， the modern research of Chinese and western medicines shows that the efficacy of Chinese herbal monomers， single Chinese herbs or Chinese herbal compounds in treating epilepsy is directly or indirectly related to their regulation of signaling pathways. To be specific， they control epileptic seizures and alleviate epileptic brain injury by regulating the expression of key molecules in corresponding signaling pathways. This paper summarized the research progress in China and abroad as follows： ①Tangeretin and ginkgolide B inhibit apoptosis and oxidative stress by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. ②Baicalin and osthol suppress autophagy by inhibiting the mammalian target of rapamycin （mTOR） signaling pathway. ③Ganoderan and astragaloside reduce apoptosis by inhibiting the mitogen-activated protein kinase （MAPK） signaling pathway. ④Salidroside and resveratrol reverse oxidative stress and apoptosis by activating the nuclear factor E2-related factor 2/antioxidant reaction element/heme oxygenase 1 （Nrf2/ARE/HO-1） signaling pathway. ⑤Curcumin and baicalin diminish inflammatory response and apoptosis by inhibiting the nuclear transcriptional factor-κB （NF-κB） signaling pathway. The above summary is expected to provide reference for the in-depth study and clinical application of TCM for the treatment of epilepsy.

Enlightenment of international pharmacovigilance system on establishment of pharmacovigilance system of Chinese medicine / 中国中药杂志

Pharmacovigilance system is an extension of the original adverse drug reactions monitoring and reporting system as well as an internationally recognized basic system that must be matched with the whole life cycle supervision of drugs. European Union(EU)pharmacovigilance system, World Health Orgnization(WHO) Uppsala Monitoring Center system and ICH system are internationally recognized pharmacovigilance systems. They all have their own pharmacovigilance characteristics and could provide guarantee for clinical safe drug use. With the deepening of international communication, pharmacovigilance has also been developed in China. Pharmacovigilance of Chinese medicine is a new concept based on the existing pharmacovigilance system of chemical medicine and the characteristics of Chinese medicine. In ancient China, Chinese medicine also had its own ways of early warning. Ancient medical books have records on the toxicity classification, clinical pharmacovigilance and intoxication rescue of Chinese medicine. With the increase of public recognition of Chinese medicine in recent years, especially since the government issued the 13 th Five-Year Plan for the development of Chinese medicine, the pharmaceutical industry in China has paid more and more attention to the pharmacovigilance of Chinese medicine.However, the pharmacovigilance system of Chinese medicine has not yet been established, and it still needs to be explored and improved.Therefore, it is very necessary to develop the system to standardize pharmacovigilance-related activities of Chinese medicine. In this context, this study analyzed and learned the characteristics of pharmacovigilance systems of EU, ICH, and WHO Uppsala Monitoring Center, so as to provide some enlightenment for the establishment and improvement of pharmacovigilance system of Chinese medicine.

Research progress on therapeutic potential of quercetin / 中国中药杂志

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.

Five-year clinical outcomes of patients with in-stent chronic total occlusion undergoing percutaneous coronary intervention / 中华心血管病杂志

Objective: To evaluate the safety and long-term clinical efficacy of percutaneous coronary intervention (PCI) in patients with in-stent chronic total occlusion (IS-CTO) lesions. Metheds: This is a retrospective analysis. Patients with IS-CTO who underwent PCI in Fuwai hospital from January 2010 to December 2013 were enrolled. A total of 212 patients who met the inclusion criteria were included in the IS-CTO group, 212 matched patients with primary CTO lesions were included in the de novo CTO group. The incidence of complications and the success rate of PCI were compared between the two groups. Successful PCI was defined as successfully implantation of stent(s) at target CTO lesions. The primary endpoint was defined as a composite event of cardiac death and myocardial infarction (MI). Secondary endpoints including PCI success, all-cause death, cardiac death, MI, target vessel related MI, revascularization, target vessel revascularization, heart failure for rehospitalization. The patients were followed up for 5 years after PCI. Results: A total of 424 cases were included. The mean age was (57.8±10.5) years, there were 364 males in this cohort. The left ventricular ejection fraction was significantly lower ((58.7±9.2)% vs. (61.0±7.7)%, P=0.01) and the SYNTAX scores was significantly higher (19.4±8.3 vs. 15.3±10.0, P<0.01) in IS-CTO group than that in de novo CTO group. The proportion of patients with target CTO lesions in left anterior descending artery was significantly higher (42.9% (50/212) vs. 23.6% (91/212), P<0.01) in IS-CTO group than that in de novo CTO group. The rate of successful PCI (71.7% (152/212) vs. 69.8% (148/212), P=0.70) and complication (40.6% (86/212) vs. 36.3% (77/212), P=0.37) was similar between the two groups. The incidence of primary endpoint at 5 years was significantly higher in IS-CTO group (10.8% (23/212) vs. 4.7% (10/212), P=0.02), which was driven by higher incidence of MI (9.0% (19/212) vs. 4.2% (9/212), P=0.05). There were a trend of higher secondary endpoints in IS-CTO group (all P>0.05). Conclusion: The safety and effectiveness of PCI are acceptable in patients with IS-CTO, but the risk of long-term cardiac death and MI is higher among patients with IS-CTO as compared to patients with primary CTO lesions.

The effects of photoperiodism and exposure to bisphenol A on hepatic lipid metabolism in female mice / 中国职业医学

OBJECTIVE: To analyze the effects and the underlying mechanisms of photoperiodism and exposure to bisphenol A(BPA) on hepatic lipid metabolism in female mice. METHODS: A 2×2 factorial design was used. The photoperiod factor was set to fixed and shifted photoperiod, and the BPA factor was set to BPA exposure(BPA group) and non-exposure(control group). Specific pathogen free female C57 BL/6 J mice were randomly divided into four groups: fixed photoperiod control group, shifted photoperiod control group, fixed photoperiod BPA group, and shifted photoperiod BPA group, with eight rats in each group. The fixed photoperiod mice received a 12 ∶12 hours light-dark cycle, and the shifted photoperiod mice experienced reversed light-dark cycle once a week. Mice in BPA group were administered a dose of BPA 50 μg/kg body weigh by gavage, while mice in control group were given a equal volume of corn oil, once per day, five days per week for 12 weeks. The body weight of mice was measured during the experiment. After 12 weeks, all mice in each group were sacrificed. Plasma was collected and the levels of biochemical parameters were measured. Liver tissues were separated for examination of lipid deposition using oil red O and hematoxylin-eosin staining, and plasma triglyceride levels were measured. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA relative expression of genes of fat metabolism in liver tissues. RESULTS: At the end of the experiment, the body weights of mice were higher than that before the experiment(all P<0.05), but there was no statistically significant difference in body weights among the four groups(all P>0.05). The levels of plasma glucose, triglyceride and activity of alanine aminotransferase were higher in shifted photoperiod mice than that in the fixed photoperiod mice(all P<0.05). The plasma aspartate transaminase level was higher in BAP group than that in control group(P<0.01). The area of lipid staining in hepatic tissue was larger in the shifted photoperiod control group, fixed photoperiod BPA group and shifted photoperiod BPA group(all P<0.05), and hepatic lipid droplets aggregation was increased in these three groups compared with the fixed photoperiod control group. The mRNA relative expression of acetyl-coenzyme A carboxylase alpha(Acaca) was higher in the fixed photoperiod BPA and shifted photoperiod control groups(all P<0.05), compared with the fixed photoperiod control group. The relative expression of Acaca mRNA was lower in the shifted photoperiod BPA group than that in the fixed photoperiod BPA group(P<0.05). The mRNA relative expression of sterol regulatory element binding protein(Srebp) 1 and Srebp2 were significantly higher in the BPA group than that in the control group(all P<0.05). CONCLUSION: Both the single shifted photoperiod or BPA exposure can increase hepatic lipid deposition in female mice. The mechanism may be related to up-regulation of the mRNA expression of Acaca, Srebp1 and Srebp2. The shifted photoperiod in combination of BPA exposure has an antagonistic effect on the expression of Acaca mRNA in liver tissues of female mice.

Research progress on antitumor activity of quercetin derivatives / 中国中药杂志

Quercetin is a kind of typical flavonoid, mainly found in various vegetables, fruits and Chinese herbs that are consumed daily, with the functions of anti-oxidation, anti-tumor, prevention and treatment of cardiovascular and cerebrovascular diseases. Quercetin is a natural compound with defined anti-tumor activity. Due to its low bioavailability and poor water solubility, quercetin has limitations in clinical application. The quercetin derivatives with good solubility, high bioavailability, metabolic stability, and low toxicity have been obtained through modification of quercetin structure. In recent years, a large number of quercetin ethers, esters, complexes, C-4 carbonyloxy substituted derivatives, A,B-ring modified compounds and other derivatives have been synthesized and tested for in vitro anticancer activity. The quercetin derivatives with anti-tumor activity synthesized in the last 5 years were reviewed in this paper.

Evaluation of cartilage regeneration by arthroscopy after high tibial osteotomy / 中国骨伤

OBJECTIVE@#To evaluate the cartilage regeneration in the knee joint by arthroscopy after high tibial osteotomy.@*METHODS@#Eleven patients were included in the study who were treated with high tibial osteotomy and underwent microscopy when the internal fixation was unloaded from September 2017 to September 2019. Among them, there were 2 males and 9 females, aged from 55 to 64 years old. The internal and external compartment pictures of the knee were taken before and after surgery of removing the internal fixation and the International Cartilage Repair Society (ICRS) grading systerm was used to evaluate the degree of cartilage damage on the medial and lateral femoralcondyles and tibial plateau. The Westrn Ontarioand Mcmaster Universities osteoarthritis index (WOMAC) and the weight bearing line (WBL) were used to evaluate the function of the knee and the alignment of the lower limb.@*RESULTS@#All 8 patients were followed up for more than 12 months, ranging from 12 to 22 months. The degenerated cartilage of the medial femoral condyle and medial tibial plateau was covered by newly regenerated cartilage. WOMAC score decreased from 102-127 to 41-52 and WBL was improved from 17%-34% to 58%-64%. All incisions healed in stageⅠ, and no complications such as internal fixation rupture and infection occurred during and after the operation.@*CONCLUSION@#High tibial osteotomy can relieve the pain of the knee and the dysfunction by adjusting lower limb alignment, and the degenerated cartilage could be regenerated in the medial femoral condyle and medial tibial plateau.

A new antiviral isoquinoline alkaloid from Thalictrum glandulosissimum / 中国中药杂志

A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.

Efficacy Analysis of Unrelated Cord Blood Transplantation in the Treatment of Juvenile Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML).@*METHODS@#The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis.@*RESULTS@#Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed.@*CONCLUSION@#UCBT is an effective treatment for children with JMML.

Clinical Analysis of "Different Diseases Saring Same Syndrome" Concept in End Stage of Different Hip Diseases / 中国实验方剂学杂志

The traditional Chinese medicine (TCM) concept that "different diseases may share the same TCM syndrome" is a unique theory explaining the relationship between diseases and TCM syndromes, which originally means that different diseases sharing the same TCM pathogenesis may develop the same syndrome. It accords with the theory of treatment based on syndrome differentiation. In clinical practices, this concept explains why the same herbal formula can be used to treat different diseases. With the development of a novel strategy to integrate the disease diagnosis and TCM syndrome differentiation, the meaning of "different diseases may share the same TCM syndrome" has also changed. It means that different diseases share the same TCM pathogenesis during their progression may show the same syndrome. Osteonecrosis of the femoral head （ONFH）, hip osteoarthritis (HOA), and hip rheumatoid arthritis (HRA) are three different diseases that occur in the bones, cartilage, and synovium of the hip joint, respectively. However, they share similar clinical symptoms and TCM symptoms if they had progressed to the end-stage. In the end-stage of the disease, hip pain, restricted activity, signs of waist and knee pain, and weakened walking function, whether it is symptoms or signs or TCM syndromes, all show their similarities, reflecting the concept of different diseases may share the same TCM syndrome. This article discusses the similarity of the three diseases from the aspects of syndrome characteristics, radiographic findings, syndrome differentiation, etiology and pathogenesis, as well as clinical treatments. We found that, in addition to similar clinical signs and symptoms, the three hip osteoarthropathies in the end-stage see articular cartilage degeneration, joint space stenosis, joint effusion, synovial thickening, bone hyperplasia, and subchondral bone cystic degeneration, etc. similar X-ray performance， kidney sperm, bone marrow, only kidney sufficiency, muscles and bones can be filled with bone marrow, liver blood, main muscles, liver and blood are sufficient to support the muscles and bones, and the disease is in the advanced stage， ONFH， HOA and HRA are closely related to liver and kidney dysfunction. Insufficient liver and kidney, meridian muscle, and bone malnutrition are three common pathological mechanisms of late hip bone disease. Deficiency, waist and knee weakness, and weakness in walking have also become common symptoms. It not only provides a theoretical basis for the "same syndrome",but also helps the differential diagnosis of "different diseases", improves the fracture level of hip diseases, and enriches the connotation of "different diseases sharing the same syndrome" in Chinese medicine.

Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.