Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVES: Through the investigation of the microhardness and microstructure of permanent tooth enamel at various eruption stages during childhood, this research offers references for the early prevention of childhood dental caries. METHODS: Forty-five premolars extracted due to orthodontic reasons were collected and screened. These premolars were divided into three experimental groups according to the time since eruption: Group A (erupted for 0-1 year), Group B (erupted for 1-3 years), and Group C (erupted for 3-5 years). Additionally, the third molars that were extracted due to impaction and had not erupted were selected as the control group, with 15 teeth in each group. Samples were prepared, and the surface microhardness, microstructure, and elemental composition of the enamel were measured using Vickers microhardness tester, scanning electron microscope, and electron probe, respectively. RESULTS: Compared with that in the control group, the microhardness of enamel in groups A, B, and C increased with prolonged eruption time, the surface porosity structure decreased considerably, the contents of Na and Mg on the surface decreased, and that of F increased (P<0.05). CONCLUSIONS The microhardness and microstructure of enamel in permanent teeth at different stages vary. Permanent teeth are at a substantially higher risk of caries within one year after eruption, and early prevention should be emphasized.
Dental Enamel/ultrastructure* ; Humans ; Hardness ; Dental Caries/prevention & control* ; Microscopy, Electron, Scanning ; Tooth Eruption ; Bicuspid/chemistry* ; Dentition, Permanent ; Child ; Child, Preschool

Objective:To study the clinical value of serum microRNA-34a (miR-34a) and aryl hydrocarbon receptor nuclear transcript-like protein 1 (BMAL1) in cervical cancer and their relationship with high-risk human papillomavirus (HR-HPV) infection.Methods:The clinical data of 76 patients with cervical cancer and 50 patients with benign cervical diseases in the Affiliated Hospital of Jining Medical University from January to December 2022 were retrospectively analyzed. The expression levels of serum miR-34a and BMAL1 were detected by real-time fluorescence quantitative polymerase chain reaction, and HR-HPV infection was detected by flow fluorescent hybridization. The patients were followed up until December 2023, and the death and poor prognosis (death, tumor recurrence and progression and severe complications at 1-year of follow-up) were recorded. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of miR-34a, BMAL1 and related indexes in evaluating the poor prognosis in patients with cervical cancer at 1-year. Multivariate Cox regression analysis was used to analyze the independent risk factors for death in patients with cervical cancer. The Kaplan-Meier survival curve was used to analyze the relationship between miR-34a, BMAL1 expression and survival period, and the log-rank test was used for comparison.Results:The expression level of serum miR-34a in patients with cervical cancer was significantly lower than that in patients with benign cervical lesions (0.46 ± 0.08 vs. 0.67 ± 0.11), the expression level of serum BMAL1 was significantly higher than that in patients with benign cervical lesions (0.58 ± 0.07 vs. 0.41 ± 0.07), and there were statistical differences ( t= 12.40 and 13.34, P<0.01). The expression levels of serum miR-34a and BMAL1 in patients with cervical cancer were associated with tumor differentiation, myometrial invasion depth, lymph node metastasis, distant metastasis and International Federation of Gynecology and Obstetrics (FIGO) stage, and there were statistical differences ( P<0.05 or<0.01); they were not associated with age, menopause and pathological type, and there were no statistical differences ( P>0.05). In patients with cervical cancer, the expression level of miR-34a in patients with HR-HPV positive infection (60 cases) was significantly lower than that in patients with HR-HPV negative infection (16 cases): 0.41 ± 0.07 vs. 0.49 ± 0.08, the expression level of BMAL1 was significantly higher than that in patients with HR-HPV negative infection: 0.65 ± 0.09 vs. 0.53 ± 0.06, and there were statistical differences ( t = 3.68 and 4.24, P<0.05 or<0.01). In patients with benign cervical diseases, there were no statistical differences in the expression levels of miR-34a and BMAL1 between patients with HR-HPV positive infection (7 cases) and patients with HR-HPV negative infection (43 cases) ( P>0.05). ROC curve analysis result showed that miR-34a combined with BMAL1 had the highest sensitivity (90.4%), specificity (89.9%) and area under curve (0.911) in assessing the 1-year poor prognosis in patients with cervical cancer ( P<0.01), and the optimal cutoff values of miR-34a and BMAL1 expression level were ≤0.39 and ≥0.64. Multivariate Cox regression analysis result showed that poor differentiation, myometrial invasion depth ≥1/2, lymph node metastasis, distant metastasis, FIGO stage Ⅲ+Ⅳ, miR-34a expression level ≤0.46 and BMAL1 expression level ≥0.58 were independent risk factors for death in patients with cervical cancer ( OR = 1.857, 2.125, 2.337, 2.751, 2.457, 3.885 and 3.666; 95% CI 0.845 to 5.788, 0.726 to 5.924, 0.709 to 5.631, 0.693 to 5.727, 0.801 to 5.936, 1.244 to 6.423 and 1.031 to 5.612; P<0.01). Kaplan-Meier survival curve analysis result showed that the median survival time in cervical cancer patients with miR-34a expression level ≤0.39 and BMAL1 expression level ≥0.64 (21 cases) was significantly lower than that in the other cervical cancer patients (miR-34a expression level>0.39 or BMAL1 expression level<0.64, 55 cases): (26.4 ± 4.2) months vs. (34.2 ± 5.6) months, log-rank χ2 = 17.12, P<0.05. Conclusions:The expression level of serum miR-34a in patients with cervical cancer is significantly reduced and the expression level of BMAL1 is significantly increased, which is related to the condition, prognosis and HR-HPV infection. It can be used as a marker for the assessment of the condition and prognosis of cervical cancer. The combined detection of the two can significantly improve the sensitivity and specificity in predicting poor prognosis of cervical cancer.

Autism spectrum disorder (ASD) is one of the common neurodevelopmental disorders in children. Its etiology and pathogenesis are poorly understood. Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD. In this study, using multiple reactions monitoring proteomic technology, 16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls. Among them, CFHR3, C4BPB, C4BPA, CFH, C9, SERPIND1, C8A, F9, and F11 were found to be altered in the plasma of children with ASD for the first time. SERPIND1 expression was positively correlated with the CARS score. Using the machine learning method, we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD. We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD. The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
Child ; Humans ; Autism Spectrum Disorder/metabolism* ; Proteomics ; Brain/metabolism*

Microvascular invasion (MVI) is an independent predictor of early recurrence and poor prognosis following hepatocellular carcinoma (HCC) resection and transplantation. As a novel non-invasive diagnostic tool, radiomics can extract the quantitative imaging features of tumors and peritumoral tissues with high throughput, providing more information on tumor heterogeneity than conventional and functional imaging of visual analysis and having a good application prospect in predicting the presence of MVI in HCC patients, thereby improving the accuracy of HCC diagnosis and prognosis. The value of the multimodal radiomics method based on various imaging methods in evaluating the possibility of MVI in HCC patients is elucidated here in combination with the latest research progress.

Objective:To investigate the efficacy and safety of the modified gasless unilateral axillary approach (MGUAA) endoscopic thyroid surgery in treatment of papillary thyroid microcarcinoma (PTMC) .Methods:From Jan. 2019 to Dec. 2019, 90 patients receiving PTMC (cT1N0M0, cI stage, 8th, 2017 AJCC) therapy by modified gasless unilateral axillary approach endoscopic thyroid surgery (MGUAA group, n=41) , and conventional open thyroid surgery (OS group, n=49) were retrospectively analyzed. Ninety patients were enrolled in the study, including 14 males and 76 females,with the mean age (42.1±12.0) years.The effectiveness of central lymph node dissection (CLND) , the operation time, the types of operation, the amount of drainage, the duration of hospital stay, the related complications, the postoperative pain of neck and axillary and the cosmetic satisfaction were compared between the two groups.SPSS 25.0 statistical software was used for statistical analysis, the measurement data was expressed by ±s, paired t test was used to compare the measurement data between groups, and Chi-square test was used to campare the count date between groups. Results:The mean age (35.0±8.6) years and the amount of surgical bleeding (12.3±7.3) ml in the MGUAA group were significantly lower than those (48.1±11.1) years and (16.1±4.3) ml in the OS group ( P<0.01) , while the mean operation time (99.1±19.5) min, the mean amount of drainage (221.4±67.9) ml and the postoperative drainage tube placement time (5.0±0.8) days were significantly higher than those of (70.6±17.8) min, (98.3±63.7) ml and (3.8±1.0) days in the MGUAA ( P<0.01) . There was no significant difference in the number of lymph nodes of CLND or the duration of hospital stay between the two groups ( P>0.05) . In terms of surgical complications, the transient recurrent laryngeal nerve injury, the postoperative hematoma, the postoperative infection, and the lymphatic leakage had no significant difference between the two groups ( P>0.05) . The MGUAA group had significant advantages in avoiding the postoperative dysphagia in front of neck, the postoperative pain of neck, and cosmetic satisfaction over the OS group [ (0.0% vs 28.6%) , (14.6% vs 71.4%) , (1.1±0.3) score vs (2.4±0.5) score ( P<0.01) ]. Whereas in axillary area pain on the surgical side, the MGUAA group was inferior to the OS group ( P<0.01) . Conclusion:The modified gasless unilateral axillary approach endoscopic thyroid surgery is a feasible, safe and cosmetically operation for PTMC (cT1N0M0, cI stage, 8th, 2017 AJCC) .

A 65-year-old male patient, who had a history of chronic lymphocytic leukemia for 3 years, presented with erythematous swelling of the right cheek for 20 days and scattered papules on the back and upper extremities for 10 days. Twenty days prior to the presentation, the patient was hospitalized for disseminated herpes zoster. Skin examination showed diffuse dark red swollen plaques in the facial area under the right eyelid as well as on the right auricle and external acoustic meatus, with a sense of infiltration on palpation; scattered brown crusts were left behind at the sites of healed herpes zoster lesions, and scattered depressed scars were observed among these crusts; scattered infiltrative, mung bean- to soybean-sized, light red papules with a smooth surface were seen on the back of the neck, back and upper limbs. Histopathological examination of the facial skin lesions revealed nodular infiltration of epithelioid cells, lymphocytes and many multinucleated giant cells in the dermis and subcutaneous adipose tissue; immunohistochemical staining showed positive staining for CD68, CD20, CD79a, CD3, CD2, CD10, CD5 and Bcl-2, scattered positive staining for Ki-67, and negative staining for CD23, cyclin D1, Bcl-6, multiple myeloma oncogene 1, CD21, CD35 and myeloperoxidase. The patient was diagnosed with Wolf′s isotopic response manifesting as granulomatous inflammation after disseminated herpes zoster. The patient was treated with intravenous drips of methylprednisolone at a dose of 40 mg/d, and the skin lesions were gradually improved and subsided. No recurrence was observed during 4 years of follow-up.

Objective:To summary the clinical features of 8 cases with ankylosing spondylitis (AS) complicated with systemic lupus erythematosus (SLE).Methods:This study was conducted retrospectively from January 2007 to November 2018. Eight patients with AS complicated with SLE who were admitted to Foshan Hospital of TCM were analyzed. Bath ankylosing spondylitis disease activity index (BASDAI) was compared using t-test. Results:Four patients were female. The mean age was (31±14) years, ranged from 16 to 59 years. The average disease duration of AS was (27±30) months(ranging from 4 to 144 months). The average disease of duration SLE was (69±51) months (ranging from 1 to 80 months). All patients was human lymphocyte antigen (HLA)-B27 positive. SLE-related organ involvement included kidney in 5 cases, leukocytopenia in 8 cases, arthralgia in 6 cases, nervous system in 1 case and skin rash in 3 cases. Renal biopsy were performed in 3 patients. And 2 cases were class Ⅲ+Ⅴ lupus nephritis, another one was class Ⅳ+Ⅴ lupus nephritis.Conclusion:AS may complicated with SLE. Some drugs may be able to active the potential SLE, which should be differentiated from drug-related lupus.

To evaluate the value of prenatal ultrasound in the diagnosis of single umbilical artery( SUA ) and fetal malformation . Methods T he characteristics of the prenatal ultrasound findings of 143 fetuses with SU A in different gestational weeks were retrospectively analyzed ,and the missing side of SU A were checked . Different types of SUA combined with fetal malformation were analyzed as well as chromosomal abnormalities and so on . Results For 143 fetuses with SU A ,there were 83 cases ( 58 .0% ) with absent left umbilical artery and 60 cases ( 42 .0% ) with absent right umbilical artery ,there was no statistical difference between the two groups ( P ＞0 .05 ) . Six cases ( 4 .2% ,6/143 ) were detected at and before 20 weeks of gestation ,and the rest 137 cases were detected after 20 weeks( 95 .8% ,137/143) . T here were 121 cases ( 84 .6% ) of isolated SUA ,22 cases ( 15 .4% ) were complicated with other malformations , including 10 cases ( 45 .5% ) with absent left umbilical artery and 12 cases ( 54 .5% ) with absent right umbilical artery . T here was no statistical difference between left and right umbilical artery deletion combined with fetal malformation( χ2 ＝1 .692 ,ν＝1 , P ＞0 .05) . T here were 11 cases( 7 .7% ,11/143) with cardiovascular malformation and nine cases ( 6 .3% , 9/143 ) with digestive system malformation . Chromosome examination was performed in 23 cases . One case of trisomy 18‐trisomy and 1 case of trisomy 13‐trisomy were found to be with missing right umbilical artery and all of them were complicated with multiple deformities . Conclusions The absence of left and right umbilical artery can be combined with abnormal fetal malformation . Prenatal ultrasonography can accurately diagnose SU A and fetal malformation .