Objective To explore molecular mechanisms underlying the in vitro counteracting effect of curcumin on malignant melanoma.Methods Cultured A375 and C8161 human melanoma cells were cultivated in vitro,and randomly divided into several test groups and a control group to be treated with different concentrations of curcumin and dimethyl sulfoxide respectively for different durations.Then,methyl thiazolyl tetrazolium (MTT) assay,Transwell assay,flow cytometry and Western blot were performed to evaluate the effect of curcumin on the proliferation,invasion and cell cycle of,as well as expressions of AKT/mTOR signaling pathway-related proteins in A375 and C8161 cells respectively.Statistical analysis was carried out by using t test.Results MTT assay showed that the treatment with curcumin of 5-35 mg/L for 24-96 hours significantly inhibited the proliferation of both A375 and C8161 cells compared with that with dimethyl sulfoxide (all P ＜ 0.001),and the inhibitory effect was in a dose-dependent manner within the range of 5-15 mg/L for A375 cells and within the range of 5-10 mg/L for C8161 cells,and in a time-dependent manner from 0 to 48 hours for both cells.After treatment for 24 hours,the 50％ inhibitory concentration (IC50) of curcumin against A375 cells and C 8161 cells was 10 mg/L and 5 mg/L respectively.Transwell assay demonstrated that the invasion of A375 and C8161 cells was significantly suppressed by 72-hour treatment with curcumin at 10 mg/L and 5 mg/L respectively (both P ＜ 0.001).Flow cytometry showed that the cell cycle of A375 and C8161 cells was arrested at G2/M phase after 24-hour treatment with curcumin at 10 mg/L and 5 mg/L respectively,with significant differences in the proportion of A375 cells and C8161 cells in G2/M phase between the test group and control group (A375 cells:35.00％ ± 3.54％ vs.120.80％ ± 7.46％,P＜ 0.001;C8161 cells:19.33％ ± 4.04％ vs.85.00％ ± 9.53％,P ＜ 0.001).Western blot revealed that the expressions of AKT/mTOR signaling pathway-related proteins were decreased in A375 and C8161 cells after 24-hour treatment with 10 mg/L and 5 mg/L curcumin respectively.Conclusion Curcumin can inhibit the proliferation and invasion of A375 and C8161 cells,likely by blocking cell cycle and inhibiting activation of the AKT/mTOR signaling pathway.

Objective To screen genes differentially expressed between dermal papilla cells from occipital and vertex scalp of patients with androgenic alopecia (AGA) through a 3D culture system.Methods Dermal papilla cells isolated from the occipital scalp tissue of patients with AGA were cultured in a 2D system for several days.Then,the third-passage dermal papilla cells were subjected to a 3D culture with the presence of dihydrotestosterone (DHT) for 72 hours (experimental group).The dermal papilla cells isolated from the vertex scalp tissue of patients with AGA,which were cultured in a 3D system with dimethyl sulfoxide,but not DHT,served as the control group.Subsequently,total RNA was extracted from the cells and reversely transcribed into cDNA followed by labeling with Cy3 and hybridization to a NimbleGen microarray.Gene ontology (GO) and pathway analysis was carried out to screen differentially expressed genes between the experimental and control group.Real time PCR was conducted to validate the results of microarray analysis.Results As the genome-wide expression profile analysis showed,there were 622 genes differentially expressed between the experimental group and control group,of which,359 were up-regulated and 263 were down-regulated in the experimental group compared with the control group.The above results were corffirmed by real time PCR.GO analysis revealed that the up-regulated genes,such as the CHEK1 and Tobl genes,were mainly involved in the inhibition of cell proliferation and promotion of cell apoptosis,while the down-regulated genes,such as the BAMBI,EFNA3,Dlx3 and UCGC genes,were associated with the acceleration of cell proliferation as well as the growth and development of epidermis.Pathway analysis showed that cell circle-controlling molecules were the most abundant molecules.Conclusions Numerous signalling molecules and pathways are involved in the development of AGA,which are mainly responsible for the modulation of cell circle,proliferation and apoptosis.

Objective To investigate the clinical application of electron-beam CT(EBCT)in the diagnosis of congenital cardiovascular diverticula. Methotis Retrospective analysis of 9 patients with congenital cardiovascular diverticula confirmed by operation and pathology was done.Of them,enhanced continuous volume scan was performed on 8 patients and enhanced single slice scan was performed on one patient with an Imatron C-150 scanner.Results The group of 9 pailents included one patient with diverticulum of the left ventricle.3 patients with diverticulum of the atria and 5 patients with diverticulum of the aorta.EBCT scan and three dimensional reconstruction could demonstrate not only the origin,size,shape,Location and adjacent structure of diverticula,but also other important complicated abnormalities such as ventrieuloarterial connection disorder,cardiac sepud defect,aortic coarctation and even dissection.Conclusion EBCT is an ideal noninvasive technique in the diagnosis of congenital cardiovascular diverticula

Objective:To compare the conventional percutaneous minimally invasive plate fixation sparing pronator quadratus versus the 3-point positioning percutaneous minimally invasive palmar locking plate fixation sparing pronator quadratus for distal radial fractures.Methods:Between January 2015 and December 2017, 50 patients with distal radius fracture were treated surgically at Department of Orthopaedics, The Second Hospital of Fuzhou by percutaneous minimally invasive plate fixation sparing pronator quadratus. They were 24 males and 26 females, aged from 21 to 71 years. Conventional percutaneous minimally invasive plate fixation was conducted for 25 patients and 3-point positioning minimally invasive plate fixation for the other 25 patients. The 2 groups were compared in terms of fluoroscopic adjustments of the plate under the pronator quadratus, fracture healing time, visual analogue scale (VAS) on days 1, 3 and 7 postoperation, and wrist flexion and extension, forearm rotation and upper limb function by Disabilities of the Arm, Shoulder and Hand(DASH) scores and Gartland-Werley scores at 3 months postoperation.Results:There was no significant difference in the general data between the 2 groups, showing comparability between groups ( P>0.05). The fluoroscopic adjustments of the plate under the pronator quadratus for the conventional group (3.4±0.5) were significantly more than for the 3-point positioning group (1.1±0.3) ( P<0.05). The VAS scores on days 1, 3 and 7 postoperation for the conventional group were significantly higher than for the 3-point positioning group ( P<0.05). At 3 months postoperation, the wrist pronation was respectively 76.6°±1.9° and 82.3°±2.0°, and the Gartland-Werley scores were respectively 3.4±0.5 and 1.9±0.2 for the conventional and 3-point positioning groups, showing significant differences between the 2 groups ( P< 0.05). Conclusions:In the treatment of distal radial fractures, compared with conventional percutaneous minimally invasive plate fixation, the 3-point positioning minimally invasive plate fixation sparing pronator quadratus may minimize the damage to the pronator quadratus, be more minimally invasive, and lead to less early postoperative pain and faster functional recovery.

Objective:To establish a derivative gas chromatography method for quantitative determination of hydra-zine hydrate in afatinib maleate.Methods:Acetone-glacial acetic acid solution and DB-225 capillary column(0.25 mm×30 m × 0.25 μm)and FID was used to separate andquantitative decermine hydrazine hydrate.Results:Excellent linearity showed within the range of 1.258-50.34 μg·mL-1(r＞0.999),detection limit was 0.001％,and the recovery rate was 91.7％-107.2％.Conclusion:The method shows low testing cost,satisfac-tory repeatability,simplicity and convenience,and is valid in derivative separation and analysis of hydrazine hydrate in afatinib maleate.

Purpose/Significance To strengthen the management of scientific and technical novelty search of traditional Chinese med-icine(TCM),and to standardize the work of novelty search.Method/Process The process of"Specification for Scientific and Technical Novelty Search of Traditional Chinese Medicine"standard formulation is expounded in detail,and the key points of the standard and its application in science and technology novelty management system are analyzed.Result/Conclusion The standard can better guide the scientific and technical novelty search institutions,standardize the writing of scientific and technical novelty search reports,improve the quality of scientific and technical novelty search reports,and help promote the healthy development of scientific and technical novelty search of TCM.The scientific and technical novelty management system based on the standard improves the efficiency of novelty search.

Objective:To evaluate the clinical effectiveness and safety of Jiuwei-Zhuhuang San plus amoxilcillin sodium and sulbactam sodium in the treatment of bacterial pneumonia in children. Methods:A total of 120 patients with bacterial pneumonia in children from 1 year to 14 years old were randomly divided into the study group ( n=90) and the control group ( n=30) with ratio 3 to 1, the random sequence created by SAS software. Both groups were treated with amoxilcillin sodium for basic treatment, the observation group was treated with Jiuwei-Zhuhuang San. Both groups were treated for 1 week and followed up for 1 week. The cough frequency, clinical effective rate, symptoms and signs score, Traditonal Chinese medicine (TCM) pattern scores and adverse event rate were observed. Results:Eighteen cases were dropped and eliminated in the observation group, and 4 cases were dropped and eliminated in the control group, so 72 of observation group and 26 of control group were analyzed. After treatment, the clinical effective rate of the observation group was 27.8% (20/72), and the control group was 0% (0/26), where the difference was significant ( χ2=7.445, P=0.006). The difference of TCM syndrome score before and after treatment in the observation group (-16.8 ± 8.2 vs. -11.0 ± 5.8, t=-3.858) was lower than that of the control group ( P<0.01). There was significant difference between the two groups ( Z=-2.347, P= 0.019) in the TCM syndrome. The cough frequency of the observation group was 41.7% (30/72), and the control group was 26.9% (7/26). There wasn’t any significant differences in the cough frequency between two groups ( P>0.05). There was no statistical difference in symptoms and signs score or adverse event rate between two groups ( P>0.05). Conclusion:On the basis of amoxicillin sodium and sulbactam sodium, combined use of Jiuwei-Zhuhuang San can improve the clinical effectiveness of children with bacterial pneumonia.

Objective To study the safety and effectiveness of chloral hydrate in children undergoing ABR tests.Methods From December 2015 to March 2022,5 513 children under the age of 12 were selected for ABR ex-amination in West China Hospital of Sichuan University,who received chloral hydrate sedation(dose of 30 mg/kg).Data on administration method(mixed or direct),sleep deprivation(yes or no),failure performance(such asfailure to sleep,insufficient sedation,superficial sleep),adverse events(vomiting,irritability,etc.)were retrospectively analyzed.Total sedation failure rate,sedation failure rates in different age groups(≤0.5 years,0.5～3 years,3～12 years)and adverse event rate were calculated.Results Among the 5 513 ABR tests,199(3.61％)failed seda-tion.The sedation failure rates in different age groups(≤0.5 years,0.5～3 years,3～12 years)were 3.03％,4.31％and 3.11％,respectively.In the sedation failure tests,insufficient sedation was found in 81.91％of the tests.The incidence of adverse events was 10.55％,with most commonly vomiting.Conclusion The sedation fail-ure rate and the incidence of adverse events of chloral hydrate at 30 mg/kg were relatively low,thus chloral hydrate can be considered safe and effective at this dose.

Objectives:To report a novel mutation site in the pathogenic gene TTR of transthyretin cardiac amyloidosis(ATTR-CA),and to identify family members at risk,and provide suitable clinical diagnosis and treatment. Methods:A retrospective analysis was conducted on the clinical data of the proband with ATTR-CA who visited the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University in March 2021.The proband underwent whole exome sequencing using high-throughput methods to detect mutation genes.Sanger sequencing was used to test candidate pathogenic loci in suspected family members,and relevant literature was reviewed. Results:Among 51 individuals spanning 5 generations in the pedigree,10 family members(including the proband)carried the heterozygous TTR gene c.163A>G mutation,resulting in the amino acid residue at position 55 changing from lysine(Lys)to glutamic acid(Glu).This mutation follows an autosomal dominant inheritance pattern,with early onset in adulthood,rapid progression,and presenting as a mixed-type ATTR-CA.Five mutation carriers had different clinical manifestations,while the remaining 5 mutation carriers,who are at younger age,have not yet shown symptoms.Within the pedigree,7 individuals died(the proband's uncle[Ⅱ-1]who died from stroke at 65 years old,the rest 6 family members died from heart disease before the age of 50). Conclusions:According to the American College of Medical Genetics and Genomics guidelines,TTR gene Lys55Glu mutation is classified as likely pathogenic,this mutation site has not been reported in the literature before.Present study adds clinical evidence that might broaden the spectrum of TTR mutations.

ObjectiveTo evaluate the methodological quality of traditional Chinese medicine （TCM） diagnosis and treatment guidelines/consensus of constipation with Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ）tool， and to study the attention situation of the included Chinese patent medicines in China's National Reimbursement Drug List in the guidelines/consensus. MethodThe data of CNKI，VIP，Wanfang Data，SinoMed，PubMed and Cochrane from the inception of the databases to October 2021 were searched to collect the TCM diagnosis and treatment guidelines/consensus of constipation. Then，the diagnosis and treatment standards and recommended Chinese patent medicines were extracted. Two researchers assessed the methodological quality of the guidelines/consensus with AGREE Ⅱ tool independently. The quality of reports was evaluated by Reporting Items for practice Guidelines in HealThcare （RIGHT） Statement. The recommended Chinese patent medicines in the guidelines/consensus were compared with those in the National Reimbursement Drug List. ResultEleven consensus and 2 guidelines were included，involving 794 experts. The scores of AGREE II were clarity of presentation（59.0%），scope and purpose（44.0%），stakeholder involvement（23.1%），rigor of development （12.1%），applicability （11.1%），and editorial independence （8.3%） from high to low. Five articles were recommended at B level（recommended after revision） and 8 articles were at C level （not recommended）. The average scores of RIGHT Statement were as follows：basic information （93.59%），background （57.69%），evidence （18.46%），recommendations （20.88%），review and quality assurance （19.23%），funding，declaration and management of interests （0.00%）， and other information （0.00%）. The included guidelines/consensus recommended a total of 27 Chinese patent medicines，among which 20 were included in the National Reimbursement Drug List，with 4 species of Class A and 16 species of Class B， accounting for 74.1% of all recommended Chinese patent medicines. Ten purgative Chinese patent medicines in the National Reimbursement Drug List were recommended by the guidelines/consensus，accounting for 50% of all purgative drugs， and 8 were not recommended. There were prescriptions for purgation， for promoting digestion and removing food stagnation， for clearing heat and purging fire，and for warming the middle and dissipating cold，Tibetan medicine and Mongolian medicine. ConclusionBy the AGREE Ⅱ assessment，the methodological quality of the TCM diagnosis and treatment guidelines/consensus of constipation included in this study needed to be improved in the future. The report quality evaluated with RIGHT Statement was low. Most drugs included in the National Reimbursement Drug List were paid attention in the TCM diagnosis and treatment guidelines/consensus of constipation. Moreover，the drugs included in the National Reimbursement Drug List could basically fulfill the clinical needs reflexed from the guidelines/consensus recommendations. However， the reasons of some drugs failing to be included in the National Reimbursement Drug List needed to be studied in the future.