Effect of Extracts from Veronica peregrine on Breast Cancer Cell-induced Osteoclastic Bone Metastasis via Inhibiting Runx2 Activation / 中国实验方剂学杂志

ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina （EVP） on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells， a human breast cancer cell line， into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 （Ck-19） gene in mouse bone marrow was determined by nested polymerase chain reaction（PCR） to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages （BMMs）， we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB （RANK）， Runt-related transcription factor 2 （ Runx2 ）， phosphorylated Runx2 （p-Runx2）， and matrix metalloproteinase-9 （MMP-9） in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases （MMPs）. ResultCompared with that in the blank group， Ck-19 expression was down-regulated in EVP groups （P<0.05）. The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand （sRANKL）， which was inhibited by EVP （P<0.05）. The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group， while EVP groups had lower cathepsin K levels than sRANKL group （P<0.05）. Compared with the blank group， the sRANKL group showed up-regulated RANK expression， Runx2 phosphorylation， and MMP-9 expression （P<0.05）， while the expression levels of RANK， p-Runx2， and MMP-9 were down-regulated when the cells were incubated with EVP （P<0.05）. Furthermore， exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group （P<0.01）， which， however， was reversed in EVP groups （P<0.05）. ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells， which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.

Effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption / 北京大学学报(医学版)

In recent years, developing new methods to accelerate orthodontic tooth movement (OTM) has attracted extensive attention in the field of orthodontic clinical and scientific research. It reduces orthodontic treatment time and risks. Over the past, various approaches have been done to accelerate orthodontic tooth movement. Several forms of corticotomy techniques have been effective in inducing rapid tooth movement. These techniques activate regional acceleratory phenomenon and create a favorable microenvironment for accelerating tooth movement. Root resorption is one of most common side effects of orthodontic treatment. It affects the long-term viability and health of teeth. However, the effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption still remains unclear. Accelerating tooth movement may have two-side effects on root resorption. Through shortening the treatment period and removing the hyalinized tissues, the acceleration of orthodontic tooth movement could reduce root resorption. The increase of root resorption might be due to the local inflammation and function of cementoclasts/odontoclasts. In this paper, we reviewed the effects of different corticotomy techniques accelerating orthodontic tooth movement on root resorption. Corticotomy techniques deal with mucoperio-steal flaps and bone tissues differently and develop towards minimally invasive. Previous studies on root resorption use two-dimensional images, including apical films and panoramic tomography, to evaluate the degree of root resorption. In recent years, researches measure the volume of root resorption accurately using cone-beam computed tomography (CBCT) and micro-CT. Most studies suggest that the root resorption during acceleration of orthodontic tooth movement through corticotomy techniques is not statistically different from that of traditional orthodontic treatment. Some studies using micro-CT have shown that the root resorption in the groups of corticotomy techniques increases compared with the control group without surgery. Because of the short duration of these studies, the clinical significance is controversial on the overall impact of corticotomy techniques on orthodontic treatment. Accelerating orthodontic tooth movement is still at its emerging phase and need further research in the form of clinical trials to illustrate the effect of corticotomy techniques accelerating orthodontic tooth movement on root resorption.

Danshen Injection Inhibits SKOV3 Cell Proliferation in Vitro by Interfering with Their Interaction with Platelets / 中国实验方剂学杂志

Objective:To investigate the inhibitory effects of Danshen injection against ovarian cancer cell proliferation induced by the interaction between platelets and cancer cells. Method:The induction of platelets on SKOV3 growth <italic>in vitro</italic> and the inhibitory effect of Danshen injection at 12，24，and 48 g·L^-1 were observed by 3-（4，5-Dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） and cell colony formation assays. The content of transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） in the platelet-tumor cell interaction system and platelet supernatant and the effect of Danshen injection on TGF-<italic>β</italic>₁secretion were detected by enzyme-linked immunosorbent assay （ELISA）. The influences of tumor cell culture supernatant on platelet aggregation and secretion and the inhibitory effect of Danshen injection were determined by microplate assay and ELISA. The effects of Danshen injection on platelet nuclear factor kappa B （NF-<italic>κ</italic>B） signaling pathway were assayed by Western Blot. Result:Compared with the blank group， the platelet induction group exhibited significantly elevated absorbance at <italic>A</italic>₅₇₀（<italic>P</italic><0.01）， while the absorbance at <italic>A</italic>₅₇₀ in the platelet + Danshen injection group was significantly lower than that in the platelet induction group （<italic>P</italic><0.01）. The comparison with the Danshen injection group revealed that the cell proliferation inhibitory rate in the platelet + Danshen injection group at the same dose was more significant （<italic>P</italic><0.01）. The number of colonies in the platelet induction group was obviously increased in contrast to that in the blank group（<italic>P</italic><0.05）， while the number of colonies in the platelet + Danshen injection group was significantly lower than that in the platelet induction group（<italic>P</italic><0.05，<italic>P</italic><0.01）. As demonstrated by comparison with the blank group， TGF-<italic>β</italic>₁content in the supernatant of the platelet induction group rose remarkably（<italic>P</italic><0.01）， whereas that in the platelet + Danshen injection group declined（<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the platelet + Danshen injection group displayed more obvious inhibition（<italic>P</italic><0.01）. Compared with the blank group， Danshen injection significantly reduced the TGF-<italic>β</italic>₁content in platelet supernatant（<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant change in the content of TGF-<italic>β</italic>₁in SKOV3 supernatant treated with Danshen injection. The platelet aggregation， thromboxane A₂（TXB₂）， and serotonin （5-HT） secretion in the SKOV3 cell supernatant induction group were significantly increased as compared with those in the blank group （<italic>P</italic><0.01）， while such indexes in the cell supernatant induction + Danshen injection group were obviously decreased （<italic>P</italic><0.01）. Compared with the Danshen injection （24 g·L^-1） group， the cell supernatant induction + Danshen injection group displayed more obvious inhibition at the same dose（<italic>P</italic><0.01）. Compared with the blank group， the platelet induction group exhibited obviously up-regulated phosphorylated TGF-<italic>β</italic>-activated kinase-1 （TAK-1） and NF-<italic>κ</italic>B， but down-regulated phosphorylated inhibitory protein of NF-<italic>κ</italic>B （I<italic>κ</italic>B）（<italic>P</italic><0.01）， which however were significantly reversed in the platelet + Danshen injection group<bold>（</bold><italic>P</italic><0.01）. Conclusion:Danshen injection affect the proliferation of SKOV3 cells by inhibiting their interaction with platelets， which may be related to the inhibited secretion of TGF-<italic>β</italic>₁.

Chronic sleep deprivation exacerbates cognitive and pathological impairments in APP/PS1/tau triple transgenic Alzheimer's disease model mice / 生理学报

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.

Quality control of eight substances in Changwei San based on quantitative analysis of multi-components by single-marker / 国际药学研究杂志

Objective: To establish a quantitative analysis of multi-components by single marker(QAMS)method for the simultaneous determination of jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamal-dehyde in Changwei San. Methods: The Waters Symmetry C18 column(250 mm×4.6 mm, 5 μm)was used for the separation, and the mobile phase was the acetonitrile(A)and 0.1% phosphoric acid(B)solution in a gradient elution at a flow rate of 1.0 ml/min. The detection wavelengths were set at 345 nm for jaceosidin and eupatilin, 215 nm for limoni, evodiamine and rutaecarpine, and 275 nm for cinnamyl alcohol, cinnamic acid and cinnamaldehyde. With evodiamine as an internal reference standard, the relative correction factors for the other 7 components were established and their contents were calculated with the relative correction factors to achieve the QAMS, and then the differences between the calculated values by QAMS and measured values by the external standard method(ESM) were compared to validate the accuracy and feasibility of the QAMS method. Results: Jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamaldehyde showed good linear relationships within the ranges of 0.98-19.60, 2.67-53.40, 4.06-81.20, 1.98-39.60, 2.69-53.80, 0.56-11.20, 1.49-29.80, and 8.77-175.40 μg/ml(r≥0.9992), whose average recoveries(RSD) were 98.77%(0.96%), 99.38%(1.01%), 100.02%(0.83%), 97.80%(1.40%), 98.91%(1.18%), 96.99% (1.13%), 98.09%(1. 24%)and 99.10%(0.67%), respectively. No significant difference was observed between the calculated values by QAMS and the measured values by ESM. Conclusion: The established QAMS method is simple and accurate, which might be used to evaluate the quality of Changwei San.

Analysis of single-nucleotide polymorphism of Sonic hedgehog signaling pathway in non-syndromic cleft lip and/or palate in the Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To study the relationship between Sonic hedgehog (Shh) associated single-nucleotide polymorphism (SNP) and non-syndromic cleft lip and/or palate (NSCL/P), and to explore the risk factors of cleft lip and/or palate. Many studies suggest that the pathogenesis of NSCL/P could be related to genes that control early development, in which the Shh signaling pathway plays an important role.@*METHODS@#Peripheral blood was collected from 197 individuals (100 patients with NSCL/P and 97 healthy controls). Haploview software was used for haplotype analysis and Tag SNP were selected, based on the population data of Han Chinese in Beijing of the international human genome haplotype mapping project. A total of 27 SNP were selected for the 4 candidate genes of SHH, PTCH1, SMO and GLI2 in the Shh signaling pathway. The genotypes of 27 SNP were detected and analyzed by Sequenom mass spectrometry. The data were analyzed by chi-squared test and an unconditional Logistic regression model.@*RESULTS@#The selected SNP basically covered the potential functional SNP of the target genes, and its minimum allele frequency (MAF) was >0.05: GLI2 73.5%, PTCH1 91.0%, SMO 100.0%, and SHH 75.0%. It was found that the genotype frequency of SNP (rs12674259) located in SMO gene and SNP (rs2066836) located in PTCH1 gene were significantly different between the NSCL/P group and the control group. Linkage disequilibrium was also found on 3 chromosomes (chromosomes 2, 7 and 9) where the 4 candidate genes were located. However, in the analysis of linkage imbalance haplotype, there was no significant difference between the disease group and the control group.@*CONCLUSION@#In China, NSCL/P is the most common congenital disease in orofacial region. However, as it is a multigenic disease and could be affected by multiple factors, such as the external environment, the etiology of NSCL/P has not been clearly defined. This study indicates that Shh signaling pathway is involved in the occurrence of NSCL/P, and some special SNP of key genes in this pathway are related to cleft lip and/or palate, which provides a new direction for the etiology research of NSCL/P and may provide help for the early screening and risk prediction of NSCL/P.

Effects of ultrasound-guided quadratus lumborum block on postoperative analgesia after caesarean section / 临床麻醉学杂志

Objective To investigate the effect of ultrasound-guided quadratus lumborum block (QLB) on postoperative analgesia after caesarean section.Methods Sixty parturientsscheduled for cesarean section, aged 20-40 years, ASA physical status Ⅰ orⅡ, were randomly divided into 2 groups (n = 30 each) using a random number table:QLB group (group Q) and control group (group C).Parturients in group Q received bilateral QLB with the use of 20 ml 0.33％ ropivacaine per side after surgery, while QLB was not done in group C.Both groups received patient-controlled intravenous analgesia (PCIA) after surgery which contains 800 mg tramadol, 40 mg nefopam and 80 ml normal saline.The accumulative consumption of tramadol, the score of numerical rating scale (NRS) for pain at rest and on movement and the bruggrmann comfort scale (BCS) score were recorded at 4, 8, 12, 24, 48 hafter operation.The cutaneous sensory block area was determined in group Q at 4, 8, 12, 24, 48 hafter operation.The patient′s satisfaction with postoperative analgesia and adverse reactions were also recorded.Results The consumption of tramadol in group Q was significantly decreased compared with that in group C (P<0.05) at 4, 8, 12, 24, 48 hafter surgery.NRS for pain at rest at all times, NRS for pain when cough at 12, 24 hafter surgery and NRS for pain when turning over at 4, 48 hafter surgery were significantly lower, while the BCS score was higher in group Q than that in group C (P<0.05).Quadratus lumborum block affected T7-L1 dermatomes at 4, 8, 12 hafter surgery and T8-L1 dermatomes at 24 hafter surgery.The analgesic plane of quadratus lumborum block disappeared at 48 hours after operation.The patient's satisfaction with postoperative analgesia was higher in group Q compared with that in group C (P<0.05).The incidence of postoperative nausea, vomiting and dizziness was similar between the two groups.Conclusion Ultrasound-guided quadratus lumborum block can remarkably reduce the consumption of tramadol after caesarean section, lower the postoperative pain score, improve the patient′s comfort and satisfaction.

Efficacy of quadrates lumborum block for unilateral inguinal hernia repair in elderly patients / 中华麻醉学杂志

Objective To evaluate the efficacy of quadrates lumborum block for unilateral inguinal hernia repair in elderly patients. Methods Fifty-eight elderly patients with unilateral inguinal hernia of both sexes, aged 65-80 yr, with body mass index of 18-25 kg∕m2 , of American Society of Anesthesiolo-gists physical status Ⅱ or Ⅲ, scheduled for elective unilateral tension-free repair, were divided into 2 groups ( n=29 each) using a random number table method: iliohypogastric-ilioinguinal nerve block group (group T) and quadrates lumborum block group (group Q). Iliohypogastric-ilioinguinal nerve block with arteria circumflexa ilium profunda as a marker was carried out with 0. 33％ ropivacaine 20 ml under ultra-sound guidance in group T. The anterior approach to quadratus lumborum block was performed with 0. 33％ropivacaine 20 ml under ultrasound guidance in group Q. Operation was started after the height of sensory block was assessed by pin-prick test at 30 min after block. When the blocking effect did not meet the opera-tion requirements, an increment of 1％ lidocaine 2. 5 ml was given every time in the surgical field until op-eration requirements were met. Dexmedetomidine was intravenously infused at a rate of 0. 03-0. 07μg·kg-1 ·min-1 during surgery until the end of surgery to maintain Narcotrend index between 80 and 90. When postoperative visual analogue scale score >3, parecoxib sodium 40 mg was intravenously injected, and if marked pain relief was not found 10 min later, tramadol hydrochloride 50-100 mg was intravenously injected. The upper spread of sensory block and intraoperative requirement for additional local anesthetics were recorded at 30 min after nerve block. The requirement for parecoxib and tramadol was recorded within 48 h after operation. The development of inadvertent intravascular injection of local anesthetics, local anes-thetic intoxication and postoperative nausea and vomiting, nerve block of lower extremity and uroschesis was recorded. Results Skin pain disappeared at the plane of T11-L1 in group T and at the plane of T9-L1 in group Q. Compared with group T, the intraoperative requirement for and consumption of local anesthetics, postoperative requirement for parecoxib and tramadol, and postoperative incidence of nausea and vomiting were significantly decreased in group Q ( P<0. 05) . Conclusion Quadrates lumborum block provides bet-ter efficacy for unilateral inguinal hernia repair than iliohypogastric-ilioinguinal nerve block in elderly pa-tients.

Effect of different anesthetic and postoperative analgesic methods on early postoperative quality of recovery in patients undergoing radical mastectomy: efficacy of serratus plane block / 中华麻醉学杂志

Objective To evaluate the effect of serratus plane block (SPB) combined with general anesthesia and SPB with patient-controlled nerve analgesia (PCNA) after surgery on the early postoperative quality of recovery in the patients undergoing radical mastectomy.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ female patients,aged 18-64 yr,weighing 45-70 kg,scheduled for elective unilateral modified radical mastectomy under general anesthesia,were assigned into 3 groups (n=20 each) using a computer software:SPB and general anesthesia plus patient-controlled intravenous analgesia (PCIA) group (SG+PCIA group),SPB and general anesthesia plus SPB with PCNA group (SG+PCNA group),and general anesthesia plus PCIA group (G+PCIA group).Ultrasound-guided ipsilateral SPB was performed before anesthesia induction.Analgesia was maintained with propofol-remifentanilsevoflurane,rocuronium or vecuronium was intermittently injected to maintain muscle relaxation.PCIA solution contained tramadol 800 mg and flurbiprofen axetil 100 mg in 54 ml of normal saline,and the PCA pump was set up to deliver a 2 ml bolus dose,with a 15 min lockout interval and background infusion at a rate of 0.5 ml/h after a loading dose of 5 ml.The location of the indwelling catheter was confirmed again using ultrasound at the end of surgery,PCNA solution contained 1％ ropivacaine 500 mg in 250 ml of normal saline,and the PCA pump was set up to deliver a 5 ml bolus dose,with a 45 min lockout interval and background infusion at a rate of 5 ml/h after a loading dose of 5 ml.The PCA pumps were used until 48 h after surgery.The automatic key was pressed when pain scores (numerical rating scale [NRS] scores) ≥ 4 at rest or during activity (at 45° ipsilateral upper extremity-up tilt).Quality of Recovery-40 (QoR-40) score was used to assess the early postoperative quality of recovery at 24 and 48 h after surgery.NRS scores at rest or during activity were recorded at 6,8,12,24 and 48 h after surgery.The total pressing times of PCA and occurrence of adverse reactions such as respiratory depression,pruritus,infection at the puncture site or pneumothorax were also recorded.Results Compared with group G+PCIA,the postoperative QoR40 scores were significantly increased,NRS scores at rest or during activity were decreased at each time point after surgery,and the total pressing times of PCA were reduced in SG+PCIA and SG+PCNA groups,the incidence of nausea and vomiting was significantly decreased in group SG+PCIA,and the incidence of nausea and vomiting and dizziness was significantly decreased in group SG+PCNA (P＜0.05 or 0.01).Compared with group SG+PCIA,the postoperative QoR-40 scores were significantly increased at 24 h after surgery,and NRS scores at rest or during activity were decreased after surgery in group SG+PCNA (P＜ 0.05 or 0.01).Conclusion SPB combined with general anesthesia and SPB with PCNA after surgery can raise the early postoperative quality of recovery in the patients undergoing modified radical mastectomy.

Analysis of safety and efficacy of propofol used as anesthesia and deep sedation during flexible bronchoscopy in children / 中国实用儿科杂志

OBJECTIVE: To investigate the efficacy and safety of propofol used as anesthesia and deep sedation during flexible bronchoscopy in children. METHODS: The clinical data of 206 children with atelectasis who underwent flexible bronchoscopic alveolar lavage in the Endoscopy Room of the Respiratory Department of Hebei Children's Hospital from January 2016 to January 2017 were retrospectively analyzed. Children for ASAⅠ/Ⅱ level were divided into two groups according to the sedation method :there were 106 cases in the propofol group(2 mg/kg)and 100 cases in the midazolam group(0.1 mg/kg).To compare the onset time of anesthetict,heart rate(HR),respiratory rate(RR),mean arterial pressure(MAP),percutaneous oxygen saturation(SPO2)before and after anesthesia induction(T0,T1),during endoscopy placement(T2)and after awakening(T3)at 4 time points,operative duration,the waked duration of postoperation,the rate of adverse reactions(hiccups,respiratory depression)in the operation and Ramsay score between two groups. All data were analyzed by SPSS 20.0 statistical software.RESULTS:(1)There were statistically significant differences at the onset time of anestheticts,operative duration and the rate of side-effects between the two groups(P0.05).(2)There was no significant difference in MAP or SPO2 at time points of T0,T1,T2,T3(P>0.05),whereas the difference in HR and RR at time points of T1,T2,T3 between the two groups was statistically significant(P<0.05).(3)The sedative effect of propofol group was significantly better than that of midazolam group in Ramsay sedative scoring. CONCLUSION: Propofol used for anesthesia and deep sedation works fast,safely and effectively in flexible bronchoscopy for children;the time to gain consciousness is short,the operation time is short and there is fewer side effects,which is worth promoting.

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Effect of RNA Interference Targeting Gene Combined with Ultrasonic Irradiation and SonoVue Microbubbles on Proliferation and Apoptosis in Keratinocytes of Psoriatic Lesions / 中华医学杂志(英文版)

Background@#Signal transducer and activator of transcription 3 (STAT3) was strongly expressed and activated in psoriatic keratinocytes (KCs) and correlated with the severity of psoriasis. The study aimed to investigate the effects of STAT3 small interfering RNA (siRNA) combined with ultrasonic irradiation and SonoVue microbubbles on the proliferation and apoptosis in KCs of psoriatic lesions and the relative mechanisms.@*Methods@#Psoriatic KCs were transfected under four experimental conditions: (1) STAT3 siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group); (2) STAT3 siRNA only carried by Lipofectamine 3000 (L group); (3) the negative control of siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (siRNA-NC); (4) not treated as Blank. Cell Counting Kit-8 assay was used to evaluate the cell proliferation. Cell cycle analysis was detected with cycle test Plus DNA reagent kit associated with flow cytometer. FITC Annexin V apoptosis detection kit associated with flow cytometer was applied for apoptosis analysis. Fluo calcium indicator associated with flow cytometer was used to analyze intracellular free calcium concentration ([Ca]). The expressions of cyclin D1 and Bcl-xL were detected both at the mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. The obtained data were statistically evaluated by two-way analysis of variance.@*Results@#STAT3 siRNA inhibited the growth of KCs in a time-dependent manner showing the highest proliferation inhibition in LUS group with proliferation ratio of 45.38% ± 5.85% at 72h (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced an altered cell cycle distribution of KCs showing the highest increases in G2/M-phase population up to 18.06% ± 0.36% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced late apoptosis of KCs with the highest late apoptosis percentage of 22.87% ± 1.28% in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the elevation of [Ca]of KCs with the highest calcium fluorescence intensity mean of 1213.67 ± 60.51 in LUS group (P < 0.05 vs. L group, siRNA-NC, or Blank). STAT3 siRNA induced the downregulation of cyclin D1 and Bcl-xL expressions of KCs at mRNA and protein levels with the lowest expressions in LUS group with cyclin D1 expression of 51.81% ± 9.58% and 70.17% ± 4.22% at mRNA level and at protein level, respectively, and with Bcl-xL expression of 37.58% ± 4.92% and 64.06% ± 7.78% at mRNA level and at protein level, respectively (P < 0.05 vs. L group, siRNA-NC, or Blank).@*Conclusions@#STAT3 siRNA inhibited the growth and induced the apoptosis in psoriatic KCs likely partly through altering cell cycle distribution, elevating [Ca], and downregulating cyclin D1 and Bcl-xL expressions. Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.

Expressions of survivin, PI3K and AKT in keratinocytes in skin lesions and their pathogenic role in psoriasis vulgaris / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of survivin and PI3K/AKT pathway in the pathogenesis of psoriasis vulgaris (PV).</p><p><b>METHODS</b>Plaque-like lesions collected from 22 patients with PV in progressive stage and 18 normal control skin specimens were examined using immunohistochemical staining, Western blotting and real-time quantitative PCR for expressions of survivin, PI3K and AKT in the keratinocytes, and their correlation was analyzed. A small interfering RNA (siRNA) was used to knock down AKT in cultured HaCaT cells, and Western blotting was used to detect the changes in the expression of survivin. RESULTS Compared with normal skin, PV lesions showed obviously up-regulated expressions of survivin, PI3K and AKT in the keratinocytes. Survivin expression was positively correlated with PI3K (r=0.4510, P=0.0351) and AKT (r=0.4423, P=0.0393) in the keratinocytes in PV lesions. In cultured HaCaT cells, siRNA-mediated knockdown of AKT caused down-regulation of survivin expression.</p><p><b>CONCLUSION</b>Survivin and PI3K/AKT signaling pathway may participate in the occurrence and progression of PV.</p>

Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD.</p><p><b>METHODS</b>We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 frameshift mutation: c.1111dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2.</p><p><b>RESULTS</b>RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated.</p><p><b>CONCLUSIONS</b>We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.</p>

A clinical study of invasive fungal disease in children without underlying diseases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of invasive fungal disease (IFD) in children without underlying diseases.</p><p><b>METHODS</b>The clinical data of 49 children without underlying diseases who were diagnosed with IFD were retrospectively studied.</p><p><b>RESULTS</b>Fungal pathogens were detected in 37 (76%) out of 49 patients, including Cryptococcus neoformans (17 children, 46%), Candida albicans (10 children, 27%), Aspergillus (3 children, 8%), and Candida parapsilosis (3 children, 8%). Fungal pneumonia (17 children, 46%) was the most commonly seen disease, with Candida albicans as the major pathogen (9 children, 53%). The 49 children had at least one high-risk factor for infection, including the use of antibiotics, a long length of hospital stay, and invasive procedures. Of all the children, 82% did not respond well to antibiotic treatment or experienced recurrent pyrexia. Among the 24 children who underwent G tests, 17 (71%) showed positive results. All the children were given antifungal therapy, and among these children, 37 (75%)were cured, 3 (6%) were still in the treatment, 5 (10%) died, and 4 (8%) were lost to follow-up.</p><p><b>CONCLUSIONS</b>In IFD children without underlying diseases, Cryptococcus neoformans and Candida are the main pathogens, and lung infection is the most common disease. Long-term use of high-dose antibiotics may be an important risk factor for fungal infection. The IFD children without underlying diseases are sensitive to antifungal drugs and have a satisfactory prognosis.</p>

Accuracy Assessment of Three-dimensional Surface Reconstructions of In vivo Teeth from Cone-beam Computed Tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results.</p><p><b>METHODS</b>Fifty teeth from 18 orthodontic patients were assigned to three groups as NewTom VG 0.15 mm group (NewTom VG; voxel size: 0.15 mm; n = 17), NewTom VG 0.30 mm group (NewTom VG; voxel size: 0.30 mm; n = 16), and VATECH DCTPRO 0.30 mm group (VATECH DCTPRO; voxel size: 0.30 mm; n = 17). The 3D reconstruction models of the teeth were segmented from CBCT data manually using Mimics 18.0 (Materialise Dental, Leuven, Belgium), and the extracted teeth were scanned by 3Shape optical scanner (3Shape A/S, Denmark). Linear and volumetric deviations were separately assessed by comparing the length and volume of the 3D reconstruction model with physical measurement by paired t- test. Geometric deviations were assessed by the root mean square value of the imposed 3D reconstruction and optical models by one-sample t-test. To assess the influence of voxel size and CBCT system on 3D reconstruction, analysis of variance (ANOVA) was used (μ = 0.05).</p><p><b>RESULTS</b>The linear, volumetric, and geometric deviations were -0.03 ± 0.48 mm, -5.4 ± 2.8%, and 0.117 ± 0.018 mm for NewTom VG 0.15 mm group; -0.45 ± 0.42 mm, -4.5 ± 3.4%, and 0.116 ± 0.014 mm for NewTom VG 0.30 mm group; and -0.93 ± 0.40 mm, -4.8 ± 5.1%, and 0.194 ± 0.117 mm for VATECH DCTPRO 0.30 mm group, respectively. There were statistically significant differences between groups in terms of linear measurement (P < 0.001), but no significant difference in terms of volumetric measurement (P = 0.774). No statistically significant difference were found on geometric measurement between NewTom VG 0.15 mm and NewTom VG 0.30 mm groups (P = 0.999) while a significant difference was found between VATECH DCTPRO 0.30 mm and NewTom VG 0.30 mm groups (P = 0.006).</p><p><b>CONCLUSIONS</b>The 3D reconstruction from CBCT data can achieve a high linear, volumetric, and geometric accuracy. Increasing voxel resolution from 0.30 to 0.15 mm does not result in increased accuracy of 3D tooth reconstruction while different systems can affect the accuracy.</p>

Reliability assessment and correlation analysis of evaluating orthodontic treatment outcome in Chinese patients / 国际口腔科学杂志·英文版

This study aimed to assess the reliability of experienced Chinese orthodontists in evaluating treatment outcome and to determine the correlations between three diagnostic information sources. Sixty-nine experienced Chinese orthodontic specialists each evaluated the outcome of orthodontic treatment of 108 Chinese patients. Three different information sources: study casts (SC), lateral cephalometric X-ray images (LX) and facial photographs (PH) were generated at the end of treatment for 108 patients selected randomly from six orthodontic treatment centers throughout China. Six different assessments of treatment outcome were made by each orthodontist using data from the three information sources separately and in combination. Each assessment included both ranking and grading for each patient. The rankings of each of the 69 judges for the 108 patients were correlated with the rankings of each of the other judges yielding 13 873 Spearman rs values, ranging from -0.08 to +0.85. Of these, 90% were greater than 0.4, showing moderate-to-high consistency among the 69 orthodontists. In the combined evaluations, study casts were the most significant predictive component (R(2)=0.86, P<0.000 1), while the inclusion of lateral cephalometric films and facial photographs also contributed to a more comprehensive assessment (R(2)=0.96, P<0.000 1). Grading scores for SC+LX and SC+PH were highly significantly correlated with those for SC+LX+PH (r(SC+LX)vs.(SC+LX+PH)=0.96, r(SC+PH)vs.(SC+LX+PH)=0.97), showing that either SC+LX or SC+PH is an excellent substitute for all three combined assessment.

Clinical value of three kinds of helicobacter pylori detection methods / 重庆医学

Objective To discuss the clinical value of three kinds of helicobacter pylori (HP) detection methods and find out the appropriate method for clinical application of the HP detection .Methods A total of 109 patients received gastroscopy ,the efficacy of RUT ,13C-urea breath test(13C-UBT) and the immunoCard STAT helicobacter pylori stool antigen (HpSA) for detection of HP were compared .Results RUT positive rate of the two pieces of gastric mucosa (the gastric antrum and the gastric body) was 34 .86% ,higher than that of single piece of gastric mucosa (gastric antrum or stomach body ) and two pieces of gastric mucosa (stomach) ,the difference was statistically significant (P0 .05) .The diagnosis of HP infection was based on 13C-UBT ,the immunoCard STAT HpSA sensi-tivity ,specificity and accuracy were 86 .49% ,95 .83% ,92 .66% ,respectively ,which were higher than RUT .Conclusion Two pieces of gastric mucosa (the gastric antrum and the gastric body) materials is appropriate for clinical promotion RUT based solution . RUT ,13C-UBT and hpsas immune quick check card are all clinical detection of HP and reliable methods ,but hpsas immune quick check card is more suitable for clinical promotion .

Study progress of pathogenesis of primary nocturnal enuresis in children / 中华实用儿科临床杂志

Primary nocturnal enuresis is a common childhood disorder,increasingly seen as part of a heterogeneous phenomenon.Nocturnal polyuria,overactive bladder,high arousal thresholds and genetics are in various combinations,central to enuresis pathogenesis.Psychiatric problems also play important roles in the pathogenesis of primary nocturnal enuresis.There are still underlying pathophysiological mechanisms to be discussed and researched.

Clinical characteristics and prognosis of congenital solitary kidney combined with renal damage in children / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and the prognosis of congenital solitary kidney in 9 children and to find the causes of renal impairment and factors associated with the prognosis.Methods The clinical data of 9 children with congenital solitary kidney in Beijing Children's Hospital Affiliated to Capital Medical University were analyzed,retrospectively.Data of long-term prognosis were collected through follow-up study.Results Five girls and 4 boys were involved in the analysis,ranging from 3.9 to 16.0 years old.The mean inpatient age was 9.9 yearsold.The patients showed different symptoms in renal impairment of solitary kidney:9 patients with proteinuria,and 3 of them had manifestation of asymptomatic proteinuria,in the early stage,3 with abnormalities of renal functions,3 diagnosed as nephrotic syndrome,and 2 with purpuric nephropathy.In the ultrasound examination of renal morphology,4 cases had normal echo image,5 cases had enhanced echo image and 2 patients had developmental malformation of the solitary kidney.The patients received follow-up visits within 1.5 to 7.0 years.The disease deteriorated into chronic kidney disease (stage 4-5) in 3 patients,1 patient underwent dialysis treatment,1 patient developed consistent and progressive proteinuria;whereas proteinuria disappeared in 4 patients and renal functions remained normal.Conclusions The renal impairment of congenital solitary kidney is mainly manifested as proteinuria,without symptoms in the early stage.In some patients,renal impairment can deteriorate into abnormalities of renal function or renal failure.The early ultrasound screening of the urinary system is recommended.Long-term follow-up should be conducted in children of solitary kidney to find early renal impairment and take appropriate treatment for them,thus to delay the occurrence and deterioration of renal impairment.