Source analysis and health risk assessment of polycyclic aromatic hydrocarbons in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021 / 环境与职业医学

Background Polycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. Objective To identify the distribution characteristics and sources of PAHs in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. Methods From 2019 to 2021, air PM2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d−1, and the sampling flow rate was 100 L·min−1. PM2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. Results From 2019 to 2021, the annual average concentrations [M (P25, P75)] of ∑PAHs in atmospheric PM2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m−3, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m−3) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P<0.001, P<0.05). The ∑PAHs concentration distribution showed a seasonal variation, with the highest value in winter and the lowest value in summer (P<0.05). Among the atmospheric PM2.5 samples, the proportion of 5-ring PAHs was the highest, the proportion of 2-3-ring PAHs was the lowest; the proportion of 2-4-ring PAHs showed a yearly upward trend, and the proportion of 5-6-ring PAHs showed yearly downward trend (P<0.05). The characteristic ratio and PCA results suggested that the sources of sampled PAHs were mainly mixed sources such as dust, fossil fuel (natural gas), coal combustion, industrial emissions, and motor vehicle exhaust emissions. The ILCR (RILCR) of PAHs by inhalation for men, women, and children were 1.83×10−6, 2.35×10−6, and 2.04×10−6, respectively, and the annual average RILCR was 2.07×10−6, all greater than 1×10−6. Conclusion For the sampled time period, the main sources of PAHs pollution in atmospheric PM2.5 in the target district of Taizhou City are dust, fossil fuel (natural gas), coal combustion, industrial emissions, motor vehicle emissions, etc., and PAHs may have a potential carcinogenic risk to local residents.

Toxicokinetics of MDMA and Its Metabolite MDA in Rats / 法医学杂志

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

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.

Efficacy and safety of submucosal tunneling endoscopic resection for multiple submucosal tumors of upper gastrointestinal tract / 中华消化内镜杂志

In order to evaluate the efficacy and safety of submucosal tunneling endoscopic resection (STER) for the treatment of multiple submucosal tumors (SMT) in the upper gastrointestinal tract, data of 24 cases with upper gastrointestinal SMT (including 56 SMT lesions) treated at Taizhou Municipal Hospital and Shanghai East Hospital from January 2016 to June 2021 were collected for retrospective observation. The treatment effect, occurrence of major adverse events and follow-up results were analyzed. The results showed that 19 cases (79.2%) underwent tumor resection through one tunnel, and 5 cases (20.8%) underwent tumor resection through two tunnels. The length of the tunnel was 3-12 cm, with an average of 6.2 cm. The surgical time ranged from 19 to 130 minutes, with an average of 55.6 minutes. The overall resection rate was 89.29% (50/56). The hospitalization time was 2-7 days, with an average of 3.5 days. Major adverse events occurred in 2 cases (8.3%), all of which were mucosal injuries, and were cured with titanium clips and self expanding metal sealing stents. During a follow-up period of 6-64 months, with an average of 32.0 months, there was no residual tumor, tumor implantation tunnel, local recurrence, distant metastasis or death. To sum up, STER is safe and feasible for the treatment of multiple SMT in the upper gastrointestinal tract. The main resection method is single tunnel, and double tunnel is required for multiple SMT far apart.

Acupuncture for Patients with Chronic Spontaneous Urticaria: A Randomized, Sham-Controlled Pilot Trial / 中国结合医学杂志

OBJECTIVE@#To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU).@*METHODS@#A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA).@*RESULTS@#A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant.@*CONCLUSIONS@#Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).

Baicalin improves inflammatory response of human microglia by regulating cAMP-PKA-NF-κB/CREB pathway / 中国中药杂志

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 μmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 μmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 μmol·L~(-1) BAI significantly increased the SOD activity and 5 μmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1β, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.

Clinical study of intercondylar fossa formation to prevent intercondylar fossa impingement after high tibia osteotomy / 中国骨伤

OBJECTIVE@#To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy.@*METHODS@#From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement.@*RESULTS@#All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05).@*CONCLUSION@#Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.

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.

Nifedipine promotes formation of autophagosomes and enhances expression of Beclinl in hepatoma cell line Huh-7 / 中国药理学通报

Aim To investigate the effect of nifedipine on the formation of autophagosomes in hepatoma cell line Huh-7 and its mechanism.Methods Different concentrations of nifedipine were used to interfere with the proliferation of Huh-7 cells in vitro.The effect of nifedipine on the proliferation of Huh-7 cells was detected by cell proliferation experiment and colony formation experiment.The expressions of Beclin1 and LC3B-Ⅱ were detected by Western blot.The effect of nifedipine on the formation of autophagosomes in Huh-7 cells was observed by laser scanning confocal microscopy.Results Nifedipine significantly inhibited the proliferation of Huh-7 cells in a time-and concentration-dependent manner.The IC50 of nifedipine on day 2 was 22.7 mg·L-1.Nifedipine at the concentration of 25 mg·L-1 significantly reduced the colony formation rate of Huh-7 cells compared with the control group, and the inhibition rate of colony formation was(95.46±0.45)%.Western blot analysis showed that nifedipine significantly up-regulated the protein expression levels of Beclin1 and LC3B-Ⅱ.The amount of autophagosomes in nifedipine group cells were more than that of control group, which was observed by laser scanning confocal microscopy.Conclusions Nifedipine significantly inhibits the proliferation of Huh-7 cells and promotes the formation of autophagosomes, which may be related to the up-regulation of Beclin1 protein expression by nifedipine.

Effect of polycomb group facor 1 on the enrichment of colorectal cancer stem cells and its mechanism / 解剖学报

Objective To explore the effect of epigenetic regulator polycomb group factor I ( PCGFI) on the enrichment of colorectal cancer stem cells and its mechanism. Methods Meta-analysis was used to predict the expression of PCGFI in normal and colorectal cancer tissues. The gene expression of PCGFI in colorectal cancer tumor cells and normal intestinal epithelium cells was detected by Real-time PCR. PCGFI loss-of-function subclone was generated in HCT116, and sternness was evaluated by spheroid formation. The effects of PCGFI on sternness markers and the key proteins in Wnt and Notch pathways were detected by Oncomine and GEPIA database, Real-time PCR and Western blotting. Results PCGFI was markedly upregulated in colorectal cancer cells and tissues. PCGFI knockdown strongly inhibited tumor sphere formation of HCT116 and sternness markers expression. There was a positive correlation between PCGFI and the key proteins in Wnt and Notch pathways. PCGFI knockdown reduced the expression of (3-catenin in Wnt signaling pathway. Conclusion PCGFI affects the enrichment of colorectal cancer stem cells and regulates the expression of key proteins in the signal pathway which is related to colorectal cancer stem cells self-renewal.

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.

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.

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.

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.

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.

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.

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.