Clinical phenotypic and genotypic analysis of 5 pediatric patients with β-ketothiolase deficiency / 中华儿科杂志

Objective: To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD). Methods: The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children's Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed. Results: The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant. Conclusions: β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

Effects and mechanism of Setaria italica extract on improving sleep in insomnia mice / 中国药房

OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group， model group， positive control group （diazepam， 2.6 mg/kg）， and S. italica extract low-dose， medium-dose and high-dose groups （1.2， 2.4， 4.8 g/kg）， with 10 mice in each group. Except for the blank group， all other groups received intraperitoneal injection of para-chlorophenylalanine （PCPA） to establish the insomnia model. After modeling， the blank group and model group were given a constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， with a volume of 0.01 mL/g， once a day， for 7 consecutive days. After the administration， the open-field test was conducted to observe the praxiological changes of mice， and to determine the levels of 5-hydroxytryptamine （5-HT） and 5-hydroxyindoleacetic acid （5-HTAA） in the hippocampal tissue， as well as the contents of 5-HT， brain-derived neurotrophic factor （BDNF）， interleukin-2 （IL-2）， IL-6， B-cell lymphoma-2 （Bcl- 2）， and Bcl-2-associated X protein （Bax） in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB （PI3K/Akt/NF-κB） signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group， the total exercise time of mice in S. italica extract high-dose group was significantly prolonged， but the total rest time was significantly shortened （P＜0.01）； the number of standing times and modification times were significantly reduced （P＜ 0.01）. The contents of 5-HT， BDNF， and Bcl-2 in serum， and Bcl-2/Bax were significantly increased， while the contents of IL-2， IL-6， and Bax were significantly reduced （P＜0.05 or P＜ 0.01）. The content of 5-HTAA in the hippocampal tissue and 202104010910029）；the phosphorylation levels of PI3K and Akt proteins were increased significantly， while the phosphorylation level of NF-κB p65 protein was decreased significantly （P＜0.05）.CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice， and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.

Biological Functions and Mechanism of Casein KinaseHrr25 / 中国生物化学与分子生物学报

Hrr25 is a member of the casein kinase 1 family in Saccharomyces cerevisiae and has serine / threonine protein kinase activity. It can function by phosphorylating a variety of proteins. The substrate proteins of Hrr25 include autophagy related proteins, COPII (coat protein complexes II) vesicle coat proteins Sec24 and Sec23, eukaryotic translation initiation factor 6, γ- Tubulin tub4, and extender complex protein 1, etc. In addition, Hrr25 can also interact with meiotic recombinant protein Rec8, Nucleoporin Nup53, transcription regulator Crz1, and transcription activator Haa1, etc. A variety of interacting proteins of Hrr25 enable it to play a role in autophagy, vesicular transport, microtubule assembly, meiosis, mitosis, DNA repair, ribosomal biogenesis, weak organic acid stress and other biological processes. In order to better understand the action mechanism of Hrr25 in various biological processes and the relationship between various biological processes, this paper summarizes the biological functions and action mechanism of Hrr25, and the potential significance of its research, so as to provide a theoretical basis for the further research of Hrr25.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Changes of Nogo-A expression in hippocampus and striatum of rats under low estrogen condition / 解剖学报

[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.

Research on serum metabolic markers of menopausal syndrome based on / 中国临床药理学与治疗学

AIM: To find specific metabolic markers for women entering peri-menopausal period and patients with menopausal syndrome based on

Mechanism of autophagy induced by osthole through PINK1/Parkin pathway in HeLa cells / 中国药理学通报

Aim To investigate the potential mechanism of osthole promoting autophagy in cervical cancer HeLa cells. Methods HeLa cells were treated with various concentrations of Osthole(0,10,20,40,80,160,240,320 mg·L-1). MTT was used to detect cell vitality. Transmission electron microscopy(TEM)was used to observe the morphology of HeLa cells after osthole intervention. Mondane sulfonyl cadaverine(MDC)staining was used to dectect the level of autophagy. Western blot was employed to analyze the expression levels of mitochondrial protein MFN1 and DPR1. JC-1 flourescence probe was applied to detect mitochondrial membrane potential. Flow cytometry was used to deteminet the release of reactive oxygen species(ROS). A transplanted tumor model of cervical cancer was established in vivo in nude mice. Western blot was used to detect the protein expression levels of PINK1,Parkin and LC3Ⅱ/. Results Osthole could inhibit the proliferation of HeLa cells significantly. Transmission electron microscopy showed that typical autophagosomes were formed in HeLa cells after osthole intervention. The fluorescence intensity of MDC was enhanced. The expression of mitochondrial fusion protein MFN1 was down-regulated after HeLa cells pretreated with osthole,and mitochondrial fission protein DRP1 was up-regulated. Mitochondrial membrane potential decreased. ROS production of HeLa cells was increased by flow cytometry,which could be reversed by autophagy inhibitor 3-MA. Tumor weight in nude mice was inhibited by osthole obviously,which might restrain cervical cancer. Western blot result indicated that the key factors of mitochondrial autophagy PINK1,Parkin and LC3Ⅱ/ratio were up-regulated in HeLa cells. Conclusions Osthole could induce autophagy in HeLa cells and its mechanism may be related to ROS production and PINK1/Parkin pathway.

Effects of DNMT3A on mouse cardiac fibroblast proliferation and migration under high glucose environment / 中国药理学通报

Aim To investigate the effect of DNA methyltransferase 3A (DNMT3A) on the proliferation and migration of cardiac fibroblasts (CFs) in C57 mice under high glucose environment. Methods The hearts of C57 mice were taken from 1 to 3 days. After cutting and digesting, CFs were extracted by differential adherance centrifugattion and observed under microscope. After cell attachment, the cells were cultured under low glucose (5.5 mmol • L

Effects of YTHDF2 on proliferation and migration of activated hepatic stellate cells / 中国药理学通报

Aim To investigate the effect of YTHDF2 on the proliferation and migration of activated hepatic stellate cells(HSCs). Methods 5 jjLg • L

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol / 中西医结合学报

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

PROSI Mutation With Clinical Heterogeneity in Protein S Deficiency:Report of One Case / 中国医学科学院学报

Reduced protein S activity is one of the high-risk factors for venous thromboembolism.Hereditary protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene.We reported a female patient with a mutation of c.292 G>T in exon 3 of the PROS1 gene,which was identified by sequencing.The genealogical analysis revealed that the mutation probably originated from the patient's mother.After searching against the PROS1 gene mutation database and the relevant literature,we confirmed that this mutation was reported for the first time internationally.

Mining and identification of a biosynthetic gene cluster producing xanthocillin analogues from Penicillium chrysogenum MT-40, an endophytic fungus of Huperzia serrata / 生物工程学报

Xanthocillin is a unique natural product with an isonitrile group and shows remarkable antibacterial activity. In this study, the genome of an endophytic fungus Penicillium chrysogenum MT-40 isolated from Huperzia serrata was sequenced, and the gene clusters with the potential to synthesize xanthocillin analogues were mined by local BLAST and various bioinformatics analysis tools. As a result, a biosynthetic gene cluster (named for) responsible for the biosynthesis of xanthocillin analogues was identified by further heterologous expression of the key genes in Aspergillus oryzae NSAR1. Specifically, the ForB catalyzes the synthesis of 2-formamido-3-(4-hydroxyphenyl) acrylic acid, and the ForG catalyzes the dimerization of 2-formamido-3-(4-hydroxyphenyl) acrylic acid to produce the xanthocillin analogue N, N'-(1, 4-bis (4-hydroxyphenyl) buta-1, 3-diene-2, 3-diyl) diformamide. The results reported here provide a reference for further discovery of xanthocillin analogues from fungi.

Advances of the novel immunosuppressant brasilicardin A / 生物工程学报

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC50=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.

Moxibustion combined with western medication for rheumatoid arthritis with blood stasis obstruction and its effect on platelet activation / 中国针灸

OBJECTIVE@#To investigate the clinical efficacy and action mechanism of moxibustion combined with western medication for rheumatoid arthritis (RA) with blood stasis obstruction.@*METHODS@#Fifty-six patients of RA with blood stasis obstruction were randomly divided into an observation group and a control group, with 28 patients in each group. The patients in the control group were treated with oral administration of leflunomide tablets and celecoxib capsules, while the patients in the observation group were treated with moxibustion in addition to the treatment used in the control group. Moxibustion was performed at bilateral Zusanli (ST 36), Shenshu (BL 23), Xuehai (SP 10), and ashi points, once every other day, three times a week. The treatment duration for both groups was 12 weeks. The TCM syndrome score, disease activity score-28 (DAS-28), rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), hemorheological indexes (whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity), serum calcium ion (Ca2+) level, and platelet count (PLT) were observed before and after treatment, and the clinical efficacy was evaluated after treatment in the two groups.@*RESULTS@#Compared with those before treatment, the TCM syndrome scores, DAS-28 scores, RF, hs-CRP, ESR, whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity, and PLT were decreased after treatment in both groups (P<0.01), with the observation group showing lower values compared with those in the control group (P<0.05). Compared with those before treatment, the serum Ca2+ levels were increased after treatment in both groups (P<0.01), and the observation group showed a higher increase than that in the control group (P<0.05). The total effective rate was 85.7% (24/28) in the observation group, which was higher than 67.9% (19/28) in the control group (P<0.05).@*CONCLUSION@#Moxibustion combined with western medication could alleviate clinical symptoms in patients with RA of blood stasis obstruction, and its mechanism may be related to the inhibition of platelet activation.

Effect of mentalization-based family therapy on depressive symptoms and non-suicidal self-injury behavior in adolescents with major depressive disorder / 四川精神卫生

BackgroundThe major depressive disorder has high prevalence among adolescents， and non-suicidal self-injury （NSSI） behaviors frequently occur among patients， therefore， major depressive disorder in adolescents has become the researching focus. ObjectiveTo explore the effect of mentalization-based family therapy （MBFT） on depressive symptoms and NSSI behavior in adolescents with major depressive disorder， and to provide references for the rehabilitation of major depressive disorder in adolescents. MethodsA total of 90 adolescent patients with major depression disorder who met the diagnostic criteria of International Classification of Diseases， 10th edition （ICD-10） for depressive disorders and attended Wuhan Mental Health Center from January to December 2022 were selected， and were assigned into study group （n=44） and control group （n=46） using random number table method. All participants received routine intervention， based on this， study group added a 60-minute MBFT intervention once a week for 8 weeks. Before the intervention and at the end of 1st， 2nd，4th and 8th week，the two groups were assessed using Hamilton Depression Scale-24 item （HAMD-24）， General Self-Efficacy Scale （GSES）， Pittsburgh Sleep Quality Index （PSQI） and Ottawa Self-injury Inventory （OSI）. ResultsThe repeated measures analysis of variance reported a statistical main effect of time， main effect of group， and interaction effect between time and group at the baseline and the end of 1st， 2nd， 4th and 8th week of treatment in HAMD-24 score （F=69.621， 15.428， 29.623， P˂0.05）， OSI score （F=176.642， 37.682， 21.873， P˂0.05）， GSES score （F=215.236， 57.421， 27.857， P˂0.05） and PSQI score （F=268.541， 61.863， 33.867， P˂0.05）. Individual effect analysis discovered a statistical difference between study group and control group at the end of 2nd， 4th and 8th week of treatment in HAMD-24 score （t=5.567， 8.645， 6.233， P˂0.01）， OSI score （t=3.675， 11.817， 9.632， P˂0.01）， GSES score （t=23.462， 31.709， 12.750， P˂0.01） and PSQI score （t=9.664， 22.457， 9.333， P˂0.01）. ConclusionMBFT may improve depressive symptoms， NSSI behavior， sleep quality and self-efficacy in adolescents with major depressive disorder. ［Funded by 2022 Natural Science Foundation Project of Hubei Province （number， 2022CFB483）］

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Comparative study of corneal thickness and thinnest point position of keratoconus measured by Pentacam HR and RTVue OCT / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P&#x003C;0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P&#x003E;0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

Huangdi Anxiao Capsules-containing serum protects cell model from cognitive dysfunction in diabetes via inhibiting NLRP3-mediated pyroptosis / 中国中药杂志

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.

Influence of SOX7 gene methylation on the proliferation, migration and invasion of renal cancer cells and its clinical value / 国际生物医学工程杂志

Objective:To study the clinical value of SRY-Box transcription factor 7 ( SOX7) gene methylation in renal cancer and its effect on the biological behavior of renal cancer cells. Methods:80 patients with renal cancer (the kidney cancer group) and 50 patients with benign renal disease (the control group) were selected as the research subjects. Synthetic oligonucleotide sequences (MON, UMON, and CON) were designed and transfected into A498 renal carcinoma cells. Methyl-specific PCR was used to detect the methylation status of the SOX7 gene in the tumor and adjacent tissue of the kidney cancer group as well as in the renal tissue of the control group. The relationship between SOX7 gene methylation and clinicopathological factors was analyzed. The migration and invasion of A498 renal cancer cells in the MON group, UMON group, and CON group were detected by the Transwell chamber. Results:The SOX7 gene methylation rate in tumor tissue of the kidney cancer group was significantly higher than that of the control group and the adjacent tissue, and the difference was statistically significant (χ 2 = 67.522, P < 0.05). The SOX7 gene is methylated in renal cancer cell lines such as Caki-1, 786-O, 769-P, while it is unmethylated in A498 renal cancer cells. There were no statistical differences in the SOX7 gene methylation rate in the tumor tissue of the renal cancer group in terms of gender, age, or pathological type (all P > 0.05). There were statistical differences in the degree of differentiation, maximum tumor diameter, lymph node metastasis, tumor number, and TNM staging in the renal cancer group in terms of tumor tissue SOX7 gene methylation rate (all P < 0.05). After transfection with MON, the SOX7 gene methylation of A498 renal cancer cells could be successfully induced, and the day-1 to day-7 cell viability, cell migration, and invasion numbers of A498 renal cancer cells in the MON group were significantly higher than those in the UMON group and the CON group ( P < 0.05). Conclusions:Hypermethylation of the SOX7 gene can promote the proliferation, migration, and invasion of renal cancer cells and has important clinical value in the evaluation of the disease and prognosis of renal cancer.

Efficacy Evaluation of Apparent Diffusion Coefficient in the Treatment of Uterine Fibroid by Magnetic Resonance Guided Focused Ultrasound Surgery / 中山大学学报(医学科学版)

ObjectiveTo assess the value of apparent diffusion coefficient （ADC） in the treatment of uterine fibroid using magnetic resonance guided focused ultrasound surgery （MRgFUS）. MethodsThe MRI and clinical data of 56 patients with uterine fibroid before， at 3 and 6 months after MRgFUS treatment， at Foshan Hospital of Traditional Chinese Medicine from December 2018 to October 2022， were retrospectively analyzed. The correlation between the ADC value and lesion volume， symptoms severity score （SSS） and uterine fibroid symptoms quality of life questionnaire （UFS-QOL） were analyzed. ANOVA was used to compare the differences in related parameters before and after treatment， and Pearson’s method was performed to analyze data correlation. ResultsThere were significant differences in ADC value ［（1.11±0.13）， （1.84±0.09）， （2.12±0.24），×10-3/（mm2/s）］， lesion volume （102±35.30， 56.70±18.88， 46.93±18.99，cm3）， SSS （36.73±11.74， 21.77±10.21， 17.66±9.30） and UFS-QOL score （59.05±17.48， 76.54±16.50， 82.46±12.37） between before treatment and each time point after treatment （F value was 557.837， 73.589， 53.976 and 37.606， respectively， all P<0.05）. The ADC values were negatively correlated with lesion volume and SSS， and positively correlated with UFS-QOL score， with correlation coefficients of -0.586， -0.630 and 0.592， respectively （all P<0.05）. ConclusionThe ADC value has clinical significance for the treatment of uterine fibroid using MRgFUS.