Sleep deprivation refers to the loss of sleep caused by self-inflicted or external factors. There is increasing evidence that pregnancy is prone to sleep deprivation, which not only disrupts maternal functions but also affects offspring′s cognitive function. This article reviews the effects of sleep deprivation during pregnancy on offspring cognition and its underlying mechanisms, in order to establish a foundation for developing scientifically sound sleep strategies during pregnancy and to provide clinical insights for improving the neurodevelopment and cognitive function of offspring.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

OBJECTIVE: To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them. METHODS: DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population. RESULTS: Novel mutation of c.430 -1G>C was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2T>G at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1G>C could lead to the production of the two CD36 mRNA transcript variants: c.429_430ins［430-17_430-2;C］(p.Ala144fsTer1) and c.430_609del(p.Ala144_Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2T>G could lead to the production of CD36 mRNA transcript variant of c.819_1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1G>C was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2T>G was 2.73% (3/110) and 0 (0/296), respectively. CONCLUSION This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.
Blood Platelet Disorders ; China ; Genetic Diseases, Inborn ; Humans ; Mutation ; RNA Splicing

Objective: To explore the feasibility of high-throughput texture analysis in the distinction of single brain metastases (SBM) from high-grade gliomas (HGG) and validate the established model. Methods: A total of 86 patients who were histologically diagnosed with SBM or HGG were retrospectively collected, including 43 patients with SBM and 43 with HGG. All of patients were performed preoperative conventional head magnetic resonance imaging (MRI) scans. A total of 236 fluid-attenuated inversion recovery (FLALR) images containing the information of tumors were selected from the MRI images and each image was considered as an object. The training set had 200 images, including 106 from SBM group and 94 from HGG group, whereas the validation set had 36 images, including 19 from SBM group and 17 from HGG. After images preprocessing, images segmentation, features extraction, and features selection, a radiomic diagnostic model was finally established using the training set. The diagnostic performance of the diagnostic model was evaluated using a receiver operating characteristic (ROC) curve. Hierarchical clustering analysis was used to evaluate the quality of the extracted feature data and the classification effect of the model. The model was further validated using the independent validation set. Results: A total of 629 features were extracted and quantified from each sample, and 41 features were selected to establish feature subsets and the diagnostic model. The classification decision function of the model is f(x)=sign and the kernel function of the model is K(x, x_i)=exp. In the training set, the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 0.845, 0.849, 0.840, 0.857 and 0.832, respectively. The area under the ROC curve reached to 0.939. Similar results were obtained in the validation set. Conclusion The high-throughput texture analysis shows high accuracy in differentiating SBM from HGG.

Objective To study the relationship between regional cerebral blood flow (rCBF) in matter lesion (WML) and cognitive impairment by arterial spin labeling (ASL).Methods Fourteen WML patients served as a WML group and 9 WML-free subjects served as a control group.Their neuropsychology was assessed and their rCBF was measured by ASL.Results The MoCA score,positive rate of symbol digit modalities test (SDMT),verbal fluency test (VFT) and digital span test forward and backward (DST F and B) were significantly lower while the trail making test-A (TMT-A) score and positive rate of Stroop B test and psychomotion speed test were significantly higher in WML group than in control group (P＜0.05,P＜0.01).The rCBF in regional WML was significantly slower in right and left semioval center,anterior and posterior horn of right and left lateral ventricle than that in normal white matter region (P＜0.01).The rCBF in WML was positively related with DST F and B (P＜0.05).The rCBF in NAWM was positively related with VFT (P＜0.01).Conclusion ASL can show the relationship between rCBF and cognitive impairment,especially executive function,attention and memory in elderly WML patients and decreased rCBF can thus increase their risk of cognitive impairment and dementia.

Objective To assess the clinical effect of oblique lumbar interbody fusion (OLIF) combined with percutaneous pedicle screw fixation on computer navigation for lumbar spondylolisthesis.Methods Total 20 patients (8 males and 12 females with average age of 54.1± 12.3 years) with lumbar spondylolisthesis were enrolled in our study during Oct.2014 and May.2016.All patients were treated with OLIF combined with percutaneous pedicle screw fixation on computer navigation.Operation time,blood loss and complications were all recorded.Clinical and Radiographic evaluation were investigated on 1 week,3 months,6 months,12 months postoperatively and final follow-up.Visual analogue scale (VAS) for low back pain and leg pain,Oswestry disability index (ODI) for low back pain and the MOS item short form health survey (SF-36) were used to evaluate the clinical efficacy of surgery.Disc height,disc angle,lumbar lordosis and degree of upper vertebral slip of patients were investigated with X-ray.Cross-sectional area of intervertebral foramina was measured with three-dimensional CT and MRI.The cross-sectional area and sagittal diameter of the thecal sac were measured on T2-weighted axial and sagittal magnetic resonance images.Accuracy of pedicle screw placement was investigated with three-dimensional CT.Fusion rate was investigated with three-dimensional CT and Xray.Results All patients were followed for 12-30 months (22.9±4.8 months).The mean operation time was (119.0±23.8) min,the mean blood loss was (57.8±20.6) ml.VAS for low back pain,VAS for leg pain,and ODI were significantly improved from (6.7± 2.6),(6.3±2.7) and 50.5％±18.2％ preoperatively to (1.3±1.0),(0.8±1.0) and 14.0％±9.6％ at the latest follow-up.The SF-36 PCS and MCS scores were improved from (27.1 ± 13.9) and (51.0±22.7) preoperatively to (67.3± 18.9) and (81.2±14.1) at the latest follow-up.Disc height,disc angle,lumbar lordosis were significantly increased from (6.0±3.6) mm,1.8°±6.2° and 39.2°±8.4° preoperatively to (10.8± 1.7) mm,6.2°±3.5° and 45.0°±7.8° at the latest follow-up.Degree of upper vertebral slip of patients was reduced from 23.5％±7.4％ preoperatively to 4.2％±3.1％ at the latest follow-up.Cross-sectional area of intervertebral foramina in CT and MRI were significantly increased from (140.6±36.0) mm2 and (78.1±31.2) mm2 before surgery to (179.8±35.6) mm2 and (141.7±29.5) mm2 at 6 months after surgery.Cross-sectional area and sagittal diameter of thecal sac were significantly increased from (73.4±29.3) mm2 and (5.2±3.2) mm before surgery to (124.5±26.6) mm2 and (9.5±2.0) mm at 6 months after surgery.Accuracy of pedicle screw placement was 95％,and fusion rate was 100％ at 6 months after surgery.There were no severe vascular and nerve injuries.Conclusion OLIF combined with percutaneous pedicle screw fixation on computer navigation has good indirect decompression effect on lumbar spondylolisthesis,and was associated with high fusion rate.It can also effectively decrease the surgical trauma,improve the accuracy of pedicle screw placement,and increase disc height,disc angle and lumbar lordosis.

OBJECTIVETo explore the molecular basis for a CD36 deficiency individual and distribution of CD36 gene mutation in Guangxi population.

METHODSA female individual was studied. CD36 phenotype was detected by monoclonal antibody immobilization of platelet antigens assay (MAIPA) and flow cytometry (FCM). The coding regions of the CD36 gene were sequenced. A DNA-based polymerase chain reaction-sequence specific primer (PCR-SSP) assay was used to verify the identified mutation. Cell lines expressing the mutant and wild-type CD36[CD36(MT) and CD36(WT)] were established, with the expression of CD36 determined by Western blotting. The distribution of CD36 gene mutation was investigated among 1010 unrelated individuals with the PCR-SSP assay.

RESULTSBoth MAIPA and FCM assays showed that the patient had type II CD36 deficiency. DNA sequencing showed that she has carried a heterozygous mutation T538C (Trp180Arg) in the exon 6 of CD36. Sequencing of cDNA clone confirmed that there was a nucleotide substitution at position 538 (538T>C). Western blotting also confirmed that the CD36 did not express on the CD36(MT) cell line that expressed the 538C mutant, but did express on the CD36(WT) cell line. The novel CD36 mutation T538C was further verified with 100% concordance of genotyping results by DNA-based PCR-SSP assay and 1010 unrelated individuals. No CD36 538C allele was detected among the 1010 individuals.

CONCLUSIONThis study has identified a novel CD36 mutation T538C(Trp180Arg)(GenBank: HM217022.1), and established a genotyping method for the novel sequence-specific primer PCR. The novel mutation is rare in Guangxi and can cause type II CD36 deficiency.

Base Sequence ; Blood Platelet Disorders ; genetics ; Blood Platelets ; cytology ; metabolism ; Blotting, Western ; CD36 Antigens ; genetics ; metabolism ; Cells, Cultured ; DNA Mutational Analysis ; DNA Primers ; genetics ; Exons ; genetics ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Genetic Diseases, Inborn ; genetics ; Genotype ; Genotyping Techniques ; methods ; Humans ; Middle Aged ; Monocytes ; cytology ; metabolism ; Mutation, Missense ; Polymerase Chain Reaction ; methods

OBJECTIVETo identify a novel human leukocyte antigen (HLA) allele HLA-B*13:92 and analyze 3D model of HLA molecule.

METHODSPolymerase chain reaction sequencing-based (PCR-SBT) was used in routine HLA typing, the B locus typing results of one sample was one base mismatch with B*13:01:01, B*58:01:01 at locus 189, The Group Specific Sequencing Products (GSSP) which target at B*13 and B*58 were used to confirm difference between the new allele and highest homologous allele, then the new allele was modeled by Swiss-model to its 3D structure.

RESULTSThe sequencing results showed that the new allele with highest homologous allele B*13:01:01 was the difference in the second exon at position 189 C>A (codon 39 GAC>GAA), 39 Asp (D) was changed to Glu (E). The amino acid substitution at residue 39 of the HLA polypeptide was located in α-helices of antigenic peptide-biding region.

CONCLUSIONThis allele is a new HLA-B allele found in Chinese Guangxi Zhang population and has been designated as HLA-B*13:92 by the World Health Organization (WHO) HLA Nomenclature Committee.

Objective To compare the appearances between chronic mastitis and breast cancer on MRI and investigate the differ-ential diagnostic value.Methods MRI data of 20 patients with chronic mastitis pathologically proved by biopsy or operation were ret-rospectively analyzed.30 cases of breast cancer were contemporaneously chosen as the control group.Morphological feature and dy-namic contrast-enhanced(DCE)manifestation of the lesions were evaluated and statistical difference was compared between mastitis and breast cancer.Morphological feature included configuration,spiculated sign,ring-like enhancement,peri-focal edema,skin thick-ening,nipple involvement and axillary lymph nodes enlargement.DCE manifestation contained calculating early enhancement ratio and drawing time-intensity curve (TIC).Results There were significant statistical differences among configuration,ring-like en-hancement and peri-focal edema between mastitis and breast cancer,respectively.No statistical differences could be found among spiculated sign,skin thickening,nipple involvement and axillary lymph nodes enlargement.Early enhancement ratio in the group of mastitis was 1.1 56±0.635 while 1.253±0.499 in the group of breast cancer and there was no statistical difference between them. There were 1 1 cases with type Ⅰ TIC,6 with type Ⅱ,3 with type Ⅲ in the lesions of mastitis,while 4 with type Ⅰ,1 1 with typeⅡ,1 5 with type Ⅲ in the lesions of breast cancer and significant statistical differences could be found between two groups.Conclu-sion Mastitis usually manifests as non-mass-like lesions on MRI.Ring-like enhancement,peri-focal edema and benign type TIC can be applied to discriminate mastitis from breast cancer.

[Abstrca t] Objective To investigate the inactivation of PMS 2 gene mediated by promoter methylation and its regulatory mechanism in nasopharyngeal carcinoma (NPC).Methods Fifty-four NPC tissues, 16 normal nasopharyngeal epithelia ( NNE) , 5 NPC cell lines ( CNE1, CNE2, TWO3, HNE1 and HONE1) and 1 normal nasopharyngeal epithelial cell line (NP69) were collected.Methylation-specific PCR (MSP) was used to detect the PMS2 promoter methylation, semi-quantitative reverse transcription PCR ( qRT-PCR) was applied to determine its mRNA expression , and immunohistochemistry ( IHC) was used to detect the protein expression of PMS 2.The expressions of PMS 2 mRNA in CNE1 and CNE2 cells before and after treated with methyltransferase inhibitor 5-aza-2-deoxycytidine were analyzed by qRT-PCR.The impact of methylation and demethylation on the mRNA expression of PMS 2, and the association of mRNA and protein expression of PMS 2 with clinicopathological features of nasopharyngeal cancer were analyzed .Results Methylation of PMS2 gene was detected in all of the five NPC cell lines , but not in normal nasopharyngeal epithelial NP69 cells.The methylation rate of PMS2 gene in NPC tissues was 63%(34/54), significantly higher than that of the normal nasopharyngeal epithelia (0/16, P<0.001).The expression levels of PMS2 mRNA and protein were significantly down-regulated in the 54 NPC tissues when compared with those in the 16 NNE tissues (P<0.001), and were also significantly lower in the 34 methylated NPC tissues than those in the 20 unmethylated NPC tissues (P<0.001).After treatment with 5-aza-2-deoxycytidine, the expression of PMS2 mRNA was restored in the CNE1 and CNE2 cells.However, the expressions of PMS2 mRNA and protein were not significantly correlated with patients′age, gender, TNM stage, histopathologic type or lymph node metastasis (P>0.05 for all).Conclusions Promoter methylation -mediated inactivation of PMS2 gene participates in carcinogenesis and development of NPC .PMS2 may be a candidate tumor suppressor in the treatment for patients with inactivation of PMS 2 promoter methylation .