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.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:Analysis of subtype distribution characteristics of human papillomavirus (HPV) infection, pathological findings of HPV-positive patients operated colposcopy and cervical histopathological examination in Changsha from 2020 to 2022.Methods:Retrospective analysis of HPV infection status of 60 354 patients was treated in the First Affiliated Hospital of Hunan University of Chinese Medicine from Jan. 2020 to Oct. 2022. They were divided into<25 years old group (3 250 cases), 25-34 years old group (19 406 cases), 35-44 years old group (17 297 cases), 45-54 years old group (13 104 cases), 55-64 years old group (4 793 cases) and≥65 years old group (2 504 cases). Cervical exfoliated cells were collected from women and specimen of lesion site were collected from men. HPV genotyping detection used polymerase chain reaction (PCR) and flow fluorescence hybridization, which could detect 27 HPV genotypes. Analyze the distribution of HPV subtypes in patients of different age groups and different treatment departments. Analyze the relationship between the infection of HPV subtypes and the outcome of 224 patients with HPV positive who also underwent colposcopy and cervical histopathology. Pearson correlation test was used for correlation analysis, and two-tailed P<0.05 was statistically significant; Pearson chi-square test or continuous correction chi-square test was used to compare the rates between groups, and two-tailed P<0.05 was statistically significant; Chi-square split test was used to compare multiple sample rates. The standard test was corrected according to the number of groups and then compared. The difference was statistically significant when the two-tailed P value was less than the corrected standard test. Results:The overall positive rate of HPV was 16.4% (9 909/60 354). Among all HPV positive patients, affection of single type HPV accounted for 75.5% (7 479/9 909) and affection of multi-type HPV accounted for 24.5% (2 430/9 909). The top six HPV types with infection rates from high to low were: HPV52 22.8% (2 256/9 909), HPV58 11.1% (1 097/9 909), HPV53 10.5% (1 045/9 909), HPV16 9.0% (890/9 909), HPV61 7.8% (774/9 909) and HPV6 7.6% (750/9 909). The difference of overall infection rate between different age groups was statistically significant (χ 2=536.90, P<0.001). The HPV infection rate was the highest in the<25 years old group, 30.1% (978/3 250), and it is higher than the age groups of 25-34 years old, 15.6% (3 035/19 406), group of 35-44 years old, 14.2% (2 464/17 297), group of 45-54 years old, 16.1% (2 115/13 104), group of 55-64 years old, 19.1% (915/4 793) and group of≥65 years old, 16.1% (402/2 504), with statistical significance( P<0.001 respectively). The most common types of HPV infection were type 6, 16.7% (378/2 266) and type 11, 10.5% (239/2 266) in dermatology clinics. The positive rate of HPV16 accounted for 12/17 in cervical intraepithelial neoplasia (CIN) 3 and cervical cancer cases, it was significantly higher than that in the inflammatory cases, 25.0% (35/140) and CIN1 cases, 23.0% (11/48), the statistical values were χ 2=15.02, P<0.001 and χ 2=12.48, P<0.001, respectively, all of which were statistically significant. Conclusions:HPV infection rate is highest in young people under 25 years old. Low-risk HPV6 and 11 are the main types of skin and venereal diseases. Among the total cases, high-risk HPV52, 58 and 53 are the most common types of infection with women in Changsha. However, high-grade cervical intraepithelial neoplasia and cervical cancer are more closely related to HPV16 infection.

Objective:To analyze the clinical value of serum 2019 novel coronavirus (2019-nCoV) immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in the diagnosis of COVID-19.Methods:A total of 116 patients diagnosed with NCP in the First Affiliated Hospital of Hunan University of Chinese Medicine and the First Affiliated Hospital of Xiamen University were enrolled from January to February 2020 as the disease group. A total of 134 cases, including 84 non-NCP inpatients and 50 healthy individuals served as the control group. Serum samples from all subjects were collected. A fully-automated chemiluminescence immunoassay analyzer was used to detect the concentration of 2019-nCoV IgM and IgG antibodies in serum. The sensitivity and specificity of the 2019-nCoV IgM and IgG antibody single test and combined detection were compared using the χ 2 test. χ 2 test and Wilcoxon′s rank sum test were used to compare the positive rates and concentrations of IgM and IgG antibodies in NCP patients before and after their 2019-nCoV nucleic acid tests turning negative, respectively. The change trend of 2019-nCoV antibody concentration in the process of NCP patients was analyzed by Wilcoxon′s rank sum test. Results:The sensitivity of 2019-nCoV IgG (90.5%, 105/116) was higher than that of 2019-nCoV IgM (75.9%, 88/116), the difference was statistically significant (χ 2=8.91, P<0.05); The specificity of 2019-nCoV IgG (99.3%,133/134) was higher than that of 2019-nCoV IgM (94.0%, 126/134), the difference was statistically significant (χ 2=5.63, P<0.05). The sensitivity (89.7%,87/97) of 2019-nCoV IgM combined with IgG was higher than that of 2019-nCoV IgM, the difference was statistically significant (χ 2=6.89, P<0.05). The specificity (100%, 125/125) of 2019-nCoV IgM combined with IgG was higher than that of 2019-nCoV IgM, the difference was statistically significant (χ 2=7.70, P<0.05). After 2019-nCoV nucleic acid test converted to negative, the positive rate (9/17) and concentration [13.0 (4.9, 24.7) AU/ml] of serum 2019-nCoV IgM antibody were significantly lower than those when the nucleic acid test was positive, positive rate (15/17) and concentration [29.5 (14.0, 61.3) AU/ml], respectively (χ 2=5.10, Z=-3.195, both P<0.05). In the course of NCP, patients′ serum samples were collected from the first day of diagnosis to every three days, three times in total. The first 2019-nCoV IgM and IgG antibody concentrations [19.4 (12.4, 63.7) AU/ml, 105.8 (74.8, 126.1) AU/ml, respectively] were significantly higher than the second concentrations [15.8 (7.1, 40.3)AU/ml, 80.5 (66.7, 105.9) AU/ml], Z were-2.897,-3.179, both P<0.05. Conclusions:2019-nCoV IgG antibody has a good application value in the diagnosis of NCP. The concentration of 2019-nCoV IgM antibody has a certain correlation with the detection of 2019-nCoV nucleic acid. The combination of 2019-nCoV IgM and IgG antibodies with 2019-nCoV nucleic acid test may be the best laboratory index for the diagnosis of NCP at present.

MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules whose role in breast cancer has been gradually discovered and clinically recognized and valued. MiRNAs play a role in the regulation of related target genes and signaling pathways in breast cancer, and participate in the proliferation, apoptosis, invasion and metastasis of breast cancer cells, and have new biomarker potential in clinical diagnosis and prognosis of breast cancer. It provides new ways and methods for the clinical treatment of breast cancer, and has important value and application prospects in reducing drug resistance and enhancing drug sensitivity. This article reviews the research progress of miRNAs in the molecular mechanism, clinical diagnosis, prognosis and clinical target treatment of breast cancer, and puts some suggestions and forward for future research directions.

Objective: To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites. Methods: Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively. Results: (1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34±68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63±98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89±82.48) ng/mL, the ADA level was (6.31±4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z₁ values were 5.215, 2.549, 3.212, respectively, and Z₂ values were 6.188, 4.524, 6.38, respectively, P₁ and P₂ were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76%, 96.9%, and 92.3%, respectively, and the specificity was 80%, 64.5%, 61.6%. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691,respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64%, 96.9%, and 84.6%, respectively, and the specificities were 92.9%, 63.8%, and 80.4%, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively). Conclusions MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.

OBJECTIVE:To observe the clinical efficacy and safety of Zidan yinxie granules combined with Acitretin capsule and Compound flumetasone ointment in the treatment of psoriasis vulgaris. METHODS:A total of 97 patients with psoriasis vulgaris were divided into control group(48 cases)and observation group(49 cases)according to number random method. Control group was given Acitretin capsule 10 mg,tid,for consecutive 8 weeks,and then 10 mg,bid,for consecutive 4 weeks and Compound flumetasone ointment for external use,bid. Observation group was given Zidan yinxie granule 4 g,tid,on the basis of control group. Treatment courses of 2 groups lasted for 12 weeks. Clinical efficacy was observed in 2 groups. Psoriasis area and severity index(PASI)score,VAS score,dermatology life quality index(DLQI) score,the expression of neutrophil elastase(NE),Trappin-2 and placental calcadin(P-cad)in serum and tissue fluid of skin lesion were observed before and after treatment. Recurrence followed up for 6 months in total effective patients and the occurrence of ADR were observed. RESULTS:Two patients of observation group withdrew from the study,and 47 patients completed the study;three patients of control group withdrew from the study,and 45 patients completed the study. Total response rate of observation group was 97.87%,which was significantly higher than 84.44% of control group,with statistical significance(P<0.05). After treatment,PASI,VAS and DLQI scores,the content of NE,Trappin-2 and P-cad in serum and tissue liquid of skin lesion were significantly lower than before treatment;the observation group was significantly lower than the control group. After 6-month follow-up,recurrence rate of total effective patients in observation group(28.26%)was significantly lower than control group(47.36%),and average recurrence time of observation group [(17.91 ± 3.10)weeks]was longer than that of control group [(9.80± 3.41)weeks],with statistical significance(P<0.05). There was no statistical significance in the total incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Zidan yinxie granules combined with Acitretion capsule and compound flumetasone ointment show clinical efficacy in the treatment of psoriasis vulgaris by lowering the expression of NE, Trappin-2 and P-cad in serum and tissue liquid of skin lesion with good safety.

Objective To determine the effect of COMMD7 inhibition on invasion and migration in liver cancer stem cells (LCSCs),and investigate the possible mechanism.Methods After LCSCs were infected by shRNA lentiviral vectors of COMMD7,adhesion assay and Transwell assay were used to detect the invasion and migration,and phalloidin staining was employed to observe the morphological changes.Western blotting was adopted to measure the expression of E-cadherin,N-cadherin and Vimentin.Results COMMD7 knockdown significantly inhibited the invasion and migration of LCSCs.The relative cell quantity of adhesion was 1.00 ± 0.12 and 2.35 ± 0.20 respectively in control cells and infected cells,suggesting there were significantly more adhesive cells in the infected group (P ＜ 0.05).The relative cell quantity per visual field of migration was 1.00 ±0.04 and 0.24±0.03,and that of invasion was 1.00 ±0.05 and 0.24 ±0.04 respectively in the control cells and infected cells,and there were significantly less invasive and migrated cells in the infected group (P ＜0.05).What's more,COMMD7 knockdown also induced some morphological changes of cells corresponding to the weakened abilities of migration and invasion.All the changes above were associated with up-regulation of E-cadherin (P ＜ 0.05) and down-regulation of N-cadherin and Vimentin (P ＜0.05),the molecules related to mesenchymal-epithelial transition (MET).Conclusion COMMD7 knockdown inhibits the invasion and migration in LCSCs,which may be through its regulation on the MET course.

Objective To observe the intervention effect of premature pathological jaundice treated with conventional blue light phototherapy combined with acupoint massage plus body massage. Methods Ninety premature infants with pathological jaundice were randomized into control group 1, control group 2 and observation group, 30 cases in each group. The control group 1 was given blue light phototherapy plus oral use of vitamin B2, the control group 2 was given body massage based on the treatment for the control group 1, and observation group was given acupoint massage based on the treatment for the control group 2, the treatment for the three groups lasting for 7 continuous days. Before and after treatment, the levels of transcutaneous bilirubin (TCB), serum total bilirubin (TB), and serum direct bilirubin (DB) were observed, and then the therapeutic effects on jaundice in the three groups were compared. Results After treatment, the overall therapeutic effect and the daily decline of TCB, TB and DB in the observation group were superior to those in the two control groups, the difference being significant (P < 0.05 or P < 0.01). In the control group 2, the post-treatment average decline of TB and the decline of TCB on treatment day 4-7 were superior to those in the control group 1, the difference being significant(P<0.05). Conclusion Acupoint massage plus body massage is effective and safe for the treatment of pathological jaundice in premature infants, and the therapy being simple and practical.

Objective To explore sex differences in cognitive and behavioral characteristics in children with autism spectrum disorder (ASD) in different age.Methods The study involved 621 children(503 boys,118 girls) diagnosed with ASD from June 2013 to June 2015.Using raw scores to examine cognitive and behavioral characteristics in children with ASD based on the Psycho-Educational Profile-3rd Edition (PEP-3).The subjects were divided into two groups according age:＜4Y group and ≥ 4Y group.The sex differences of cognitive and behavioral characteristics were analyzed in different age groups.Results No sex differences were found in characteristic motor behaviors (CMB) and characteristic verbal behaviors (CVB) raw scores in ＜4Y group(P＞0.05),while girls with ASD had lower raw scores on CMB and CVB raw scores in ＞4Y group((21.56±7.33) vs (24.09±4.80),(9.79±7.05) vs (13.27±5.75) ; P＜0.05)).Girls with ASD had lower raw scores on cognitive verbal/preverbal (CVP),CMB and CVB in ～ 4Y,～5Y,and ～6Y group (P＜0.05).However,there was no sex difference on CVP,CMB and CVB in ～ 3Y and ～ 7Y group (P＞0.05).Conclusions Characteristic verbal and motor behaviors may not be obvious in girls with ASD in early childhood,which may increase the difficulties of early clinical identification.The development of cognitive ability in girls with ASD is far behind that in boys in the crucial 3-5 years old,as well as social reciprocity and characteristic behaviors.It suggests that the behavior characteristics are closely related to cognitive development.