Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To evaluate the placental micro-vascular circulation by microvascular flowing imaging (MVFI) method, and to explore the clinical value of microvascular index (MVI) for the diagnosis of fetal growth restriction (FGR).Methods:A total of 21 fetuses at 24-34 weeks of gestation at the Peking Union Medical College Hospital from October to November 2019 were enrolled in this study, including 7 fetal growth restriction (FGR) fetuses, and 14 normal fetuses as control group. The fetuses of the two groups were matched according to the gestational weeks at the ratio of 1∶2. Fetal biometry parameters were measured and the placenta was observed by two-dimensional ultrasound.Uterine artery pulse index (UtA-PI), middle cerebral artery pulse index (MCA-PI), and umbilical artery S/D ratio were evaluated by color and pulse-wave Doppler. The placenta mico-circulation was displayed by the MVFI method and MVI was measured.Results:The study included 14 normal fetuses and 7 FGR fetuses. Compared with the control group, more placenta in the FGR group manifested as thickened and heterogeneous with decreased MVI and increased UtA-PI. There was statistically significant difference in placental mean MVI between two groups ( P=0.044). Besides, a trend towards significant negative correlation was observed between MVI and placenta thickness, although this was not statistically significant ( rs=-0.35, P=0.065). MVI had a higher specificity (100%) in the prediction of FGR. Conclusions:MVFI can display the micro-circulation of the placenta, and provide a direct and quantitative assessment method for placental perfusion.

Objective:To observe the effects of pyrroloquinoline quinine (PQQ) on the mitochondrial function and cell survival of rat bone marrow mesenchymal stem cells (BMSCs) under oxidative stress, and to explore its mechanism.Methods:BMSCs of rats were cultured in vitro with Dulbecco′s minimum essential medium/F12 medium containing fetal bovine serum in the volume fraction of 10% (hereinafter referred to as normal medium). The rat BMSCs of third to fifth passages in logarithmic growth phase were selected for the following experiments. (1) The cells were divided into normal control group, normal control+ PQQ group, hydrogen peroxide (H 2O 2) alone group, and H 2O 2+ PQQ group. The cells in normal control group were cultured in normal medium for 24 hours; the cells in normal control+ PQQ group were cultured in normal medium containing 100 μmol/L PQQ for 24 hours; the cells in H 2O 2 alone group were cultured in normal medium containing 200 μmol/L H 2O 2 for 24 hours; the cells in H 2O 2+ PQQ group were pre-incubated with normal medium containing 100 μmol/L PQQ for 2 hours, and then with H 2O 2 added to the concentration of 200 μmol/L and cultured for 24 hours. The cell morphology of each group was observed under the inverted phase contrast microscope, and the cell survival rate was detected by cell count kit 8 method. (2) Five batches of cells were collected, and the cells of each batch were divided into normal control group, H 2O 2 alone group, and H 2O 2+ PQQ group. The cells in each group received the same treatment as that in the corresponding group of experiment (1). After 24 hours of culture, one batch of cells was collected for apoptosis detection by flow cytometry, and the apoptosis rate was calculated. One batch of cells was subjected to mitochondrial membrane potential assay and JC-1 fluorescent staining observation using the JC-1 mitochondrial membrane potential detection kit and the inverted phase contrast fluorescence microscope, respectively. One batch of cells was collected for mitochondrial morphology observation under the transmission electron microscope. One batch of cells was subjected to catalase (CAT) and superoxide dismutase (SOD) activity assay by CAT activity assay kit and SOD activity assay kit, respectively. One batch of cells was subjected to Western blotting for determination of protein level of Epac1, adenine monophosphate activated protein kinase (AMPK), phosphorylated AMPK, cysteinyl aspartate-specific proteinase 3 (caspase-3), and cleaved caspase-3, and the phosphorylation level of AMPK and cleaved caspase-3/caspase-3 ratio were calculated. Six replicates were measured in each group for each index except for morphological observation. Data were statistically analyzed with one-way analysis of variance and independent sample equal variance t test. Results:(1) After 24 hours of culture, compared with those in normal control group (the cell survival rate was set to 100.0%), there was an increase in cell vacuole and a decrease in cell number in H 2O 2 alone group, and the cell survival rate was significantly reduced to (74.3±2.9)% ( t=6.39, P<0.01). Compared with those in H 2O 2 alone group, the cell morphology of H 2O 2+ PQQ group was significantly improved, and the cell survival rate was significantly increased to (116.9±4.2)% ( t=6.92, P<0.01); the cell survival rate in normal control+ PQQ group was (101.2±1.1)%, close to that of control group ( t=1.06, P>0.05). (2) After 24 hours of culture, compared with (13.6±1.0)% in normal control group, the apoptosis rate of cells in H 2O 2 alone group was significantly increased to (37.1±2.0)% ( t=10.57, P<0.01). Compared with that in H 2O 2 alone group, the apoptosis rate of cells in H 2O 2+ PQQ group was significantly declined to (17.0±0.7)% ( t=9.49, P<0.01). (3) After 24 hours of culture, compared with those in normal control group, the mitochondrial membrane potential of cells in H 2O 2 alone group was depolarized, the JC-1 fluorescent dye mainly existed in the cytoplasm in the form of monomer, which emitted green fluorescence, and a significant decrease in mitochondrial membrane potential was shown ( t=4.18, P<0.01). Compared with those in H 2O 2 alone group, the mitochondrial membrane potential of cells in H 2O 2+ PQQ group was increased to normal level ( t=4.43, P<0.01), and the JC-1 fluorescent dye accumulated in mitochondria following the polarized mitochondrial membrane potential and emitted red fluorescence. (4) After 24 hours of culture, compared with that in normal control group, the mitochondrial structure of cells in H 2O 2 alone group was disordered, with disappeared mitochondrial cristae and decreased mitochondrial matrix density. Compared with that in H 2O 2 alone group, the mitochondrial structure of cells in H 2O 2+ PQQ group was regular and intact, with clearly visible mitochondrial cristae and increased mitochondrial matrix density. (5) After 24 hours of culture, compared with those in normal control group, the CAT activity of cells in H 2O 2 alone group was significantly increased ( t=4.54, P<0.05), and the SOD activity was significantly decreased ( t=3.93, P<0.05). Compared with those in H 2O 2 alone group, the CAT activity of cells in H 2O 2+ PQQ group was obviously increased ( t=8.65, P<0.01), while there was no significant change in the SOD activity ( t=0.72, P>0.05). (6) After 24 hours of culture, compared with those in normal control group, the protein expression of Epac1 of cells in H 2O 2 alone group was significantly decreased ( t=4.67, P<0.01), while the AMPK phosphorylation level and the cleaved caspase-3/caspase-3 ratio were significantly increased ( t=7.88, 3.62, P<0.01). Compared with those in H 2O 2 alone group, the protein expression of Epac1 and the AMPK phosphorylation level of cells in H 2O 2+ PQQ group were both significantly increased ( t=4.34, 16.37, P<0.01), while the cleaved caspase-3/caspase-3 ratio was significantly declined ( t=3.17, P<0.05). Conclusions:Pretreatment with PQQ can improve the mitochondrial function, reduce cell apoptosis rate, and enhance cell survival rate of rat BMSCs under oxidative stress, which may be related to the up-regulation of Epac1 protein expression, activation of AMPK signaling pathway, and down-regulation of cleaved caspase-3 protein level.

Objective To determine the fetal facial angles at 11 －38 weeks of gestation by three‐dimensional ultrasound ( 3DUS) and analyze the correlation between facial angles and gestational age( GA ) . Methods From 2013 April to 2014 February ,439 singleton fetuses ranged 11－38 weeks of gestation were enrolled in this study . T he details of mid‐sagittal plane of facial profile was confirmed with 3DUS . Four facial angels were measured in this plane ,including frontomaxillary facial angle ( FM F ) ,frontonasal angle ( FNA ) ,mandibulomaxillary facial angle( M M F) and maxilla‐nasion‐mandible angle( M NM ) . T he intra‐and interobserver reliability were calculated in first 30 cases ,intra‐class correlation coefficient( ICC) greater than 0 .75 indicated good reliability . Pearson′s correlation coefficient ( r ) ,curve estimation and polynomial regression models were used to evaluate the correlation of the fetal facial angles with GA . Results ICC of the same observer were 0 .968 ,0 .962 ,0 .974 and 0 .988 ,respectively . ICC of different observer were 0 .948 , 0 .905 ,0 .874 and 0 .889 ,respectively . T he fetal facial angles of FM F ,FNA ,M M F and M NM showed correlations with GA ( r ＝ －0 .369 ,0 .447 ,－0 .470 ,0 .386 ; all P ＝0 .000) . Using GA as the independent variable and the facial angles as the dependent variables , the best fit regressing equation was cubic polynomial :FM F＝135 .300－6 .473×GA+0 .235×GA2 －0 .003×GA3 ( R2 ＝0 .240 , P ＝0 .000 ) ;FNA＝58 .920+7 .452×GA －0 .274×GA2 －0 .003×GA3 ( R2 ＝0 .297 , P ＝0 .000 ) ;M M F＝132 .329 －5 .337× GA+0 .191× GA2 －0 .002× GA3 ( R2 ＝ 0 .304 , P ＝ 0 .000) ;M NM ＝ －24 .592+ 4 .653× GA －0 .173× GA2 + 0 .002 × GA3 ( R2 ＝ 0 .413 , P ＝ 0 .000 ) . Conclusions The development of fetal facial angles are related to GA . T he growing patterns of fetal facial angles fit with a cubic polynomial function .

Objective To explore the application value of ultrasound medical imaging workstation in quality control of ultrasound reports issued by resident doctors.Methods The pancreatic ultrasound reports of outpatients provided by resident doctors with 6 months and 12 months of training were derived from the ultrasound medical imaging workstation as 6-month group (G6M) and 12-month group (G12M),respectively.There were 1582 ultrasound reports in the G6M,including 420 for males and 962 for females,with 1318 for patients ＜ 65 years old and 264 for patients ≥ 65 years old.There were 2723 ultrasound reports in the G12M,including for 760 males and 1963 for females,with 2323 for patients ＜ 65 years old and 400 for patients ≥ 65 years old.Frequency of"unclear tail of the pancreas" in the report,standard image,and body markers were recorded.The chi-square test was used to compare patient gender,age,and the quality of resident reports between the two groups.Results The chi-square test showed that there was no significant difference in sex or age composition between the two groups (all P ＞ 0.05).The number of cases of"unclear tail of the pancreas" reported in the G6M and G12M was 554 (35.02％) and 734 (26.96％),respectively,and there was a statistical difference between the two groups (x2=31.029,P ＜ 0.001).In the reports with "unclear tail of the pancreas",the number of reports with "no map" was 8 (1.44％) and 14 (1.91％) in the G6M and G12M,respectively,and there was no significant difference between the two groups (P ＞ 0.05).As to "map without marker" and "map with marker",there were 337 (60.83％) vs 209 (37.73％) and 308 (41.96％) vs 412 (56.13％) in the G6M and G12M,respectively,and the chi-square test showed that there were significant differences between the two groups (x2=44.960 and 42.834,all P ＜ 0.001).Conclusion Ultrasound medical imaging workstation can be used for periodic spot check,evaluation,and feedback of resident reports,which has a positive role in promoting the quality control of ultrasound reports.

Objectives To evaluate the effectiveness of cognitive behavior therapy for insomnia (CBT-i) in chronic insomnia patients in terms of the improvements of psychological and sleep diary parameters. Methods Patients who met the diagnostic criteria of chronic insomnia, were divided into primary group or comorbid group. Both groups received standard CBT-i interventions. Psychological scales and sleep diaries were used to evaluate participants' severity of insomnia and psychological conditions related to insomnia at four time points:before intervention (baseline), immediate after intervention, 4 weeks and 16 weeks after intervention. Results Both groups achieved significant improvements after intervention on psychological measurements and sleep diary parameters. Such improvements were maintained at 4-week and 16-week follow-ups. The sleep diary data indicated that by the end of the intervention, there were significant differences on sleep onset latency(51.72 min to 10.53 min in primary group, P<0.01;59.26 min to 15.67min in comorbid group, P<0.01)and sleep efficiency (71％to 95％in primary group, P<0.01;68％to 90％in comorbid group, P<0.01). There were differences on sleep onset latency (10.00 min vs. 13.93 min,P<0.05), total sleep time (355.71 min vs. 327.85 min, P<0.05) and sleep efficiency (95％vs. 91％, P<0.01) in primary group and comorbid group respectively. No differences were found on wake after sleep onset in the two groups. Conclusions Chronic insomnia patients with or without comorbidities both have improvements after CBT-i. Sleep diary parameters rather than psychological measurements are different in two groups. Thus, CBT-i is an effective non-pharmaceutical therapy inpatients with chronic insomnia.

Objective: To explore the value of prenatal ultrasound in diagnosis of congenital dacryocystocele. Methods: The ultrasonographic features of 16 fetuses with congenital dacryocystocele were retrospectively reviewed and the outcome of pregnancy were followed up. Results: The median gestational week detected with prenatal ultrasound was 30.29 weeks, the mean diameter was (8.96±1.96)mm. Congenital dacryocystoceles were unilateral in 12 fetuses and bilateral in 4 fetuses, 10 were female and 6 were male. The typical ultrasonic feature was anechoic cystic mass with clear boundary in relation to the medial and inferior aspects of the fetal orbit. The dacryocystocele resolved spontaneously prenatally in 5 fetuses, resolved spontaneously after delivery in 10 fetuses. One fetus died in caesarean section due to complete placenta previa. Conclusions Congenital dacryocystitis has its characteristic ultrasonographic features, and most cases can disappear naturally in prenatal or early newborns.

Objective To investigate the sonographic diagnosis and genetic counseling of fetal cardiac rhabdomyoma.Methods Four cases of fetal cardiac rhabdomyoma diagnosed at Peking Union Medical College Hospital from August 2016 to January 2017 were enrolled in this retrospective study.The results of ultrasound,other image modalities,genetic testing,and pregnancy outcomes were analyzed.Results In all fetuses echogenic solid masses were observed in the ventricles,which were single in 2 cases and multiple in the other two cases.In two fetuses no extracardiac anomalies were identified,and in another two tuberous sclerosis was diagnosed based on the clinical features including renal cyst in one case and intracranial tubers on ultrasound and MRI in another case.There was negative family history for genetic diseases in all cases except one.After counseling,all parents opted for pregnancy termination.Autopsy was performed in 3 cases,in whom characteristic cardiac rhabdomyomas were found in left ventricle.Microscopic examination of one case showed cysts arising from tubules in both kidneys.In another case mutilple tubers were observed on the trunk.Conclusions Cardiac rhabdomyomas are characteristic on prenatal ultrasound.Targeted screening based on ultrasound and family history are helpful for the early diagnosis of tuberous sclerosis.Genetic testing should be considered in suspected cases.

Objective · To prepare the liposomal pemetrexed and investigate its effects on MCF-7 breast cancer cells in vitro and nude mice bearing MCF-7 xenograft tumors. Methods · Liposomal pemetrexed was prepared by film dispersion method. Inhibition of MCF-7 breast cancer cell lines was evaluated by CCK-8 method, and anti-tumor effects were investigated on Balb/c nude mice bearing MCF-7 xenograft tumors. Results · Liposomal pemetrexed inhibited the growth of MCF-7 cells. When the concentrations of pemetrexed were 0.20, 0.40 and 10.00 μg/mL, the cell viability in experiment group (liposomal pemetrexed) was significantly lower than that in control group (pemetrexed of same concentration gradient), with P values of 0.013, 0.035 and 0.041, respectively. Compared with blank group (same volume of PBS), the volumes and weights of tumors of nude mice in experiment group(liposomal pemetrexed) and control group (same volume of pemetrexed) were significantly lower, and the volume and weight of tumor in experiment group were also significantly lower than those in control group (P=0.000). Conclusion · Compared to bulk drug of pemetrexed, liposomal pemetrexed can inhibit the growth of MCF-7 breast cancer cells and the Balb/c nude mice bearing MCF-7 xenograft tumors.

Objective To evaluate the fetal profile (FP) line with two-dimensional and three dimensional ultrasound, to explore the changes of fetal facial profile with gestational age,and to analyze the manifestation of FP line for abnormal chromosomal fetuses. Methods FP line, which was defined as the line that passes through the anterior border of mandible and the nasion, was test on the facial mid-sagittal plane. Firstly, from April 2013 to January 2014, FP line was analyzed in 439 normal fetuses of Peking Union Medical College Hospital at 11-38 weeks of gestation. According to the relationship between FP line and fetal frontal bone,it was divided into three types: the FP line passed anteriorly, across or posteriorly to the frontal bone, respectively. When the FP line passed posteriorly to the frontal bone, the distance (F distance) between the FP line with the frontal bone was measured. Secondly, 26 pathological fetuses (21 trisomy 21 fetuses with 13-33 weeks' gestation and 5 trisomy 18 fetuses with 21-31 weeks' gestation) were analyzed respectively. Results No cases with a FP line passed anteriorly to the frontal bone were found in all of normal fetuses. Most commonly seen was that FP line passed across to the frontal bone (92.26%). The FP line passed posteriorly to the frontal bone in up to 7.74%, and the mean F distance was 0.24 cm (range, 0.10-0.51 cm). In 21 fetuses of trisomy 21, 14 cases showed the FP line passed across to frontal bone, and 4 cases showed the FP line passed posteriorly frontal bone with the F distance from 0.23 cm to 0.55 cm. Three cases with sloping forehead with FP line passed anteriroly to frontal bone. As to 5 cases of trisomy 18, 2 cases showed FP line passed across to frontal bone, and 3 cases with micrognathia had FP line passed anteriroly to frontal bone. Conclusions No cases with a FP line passed anteriorly to the frontal bone were found in normal fetuses. The FP line, as a reference line for forehead and mandible abnormality, may be a useful tool to detect second trimester profile abnormalities such as sloping forehead and retrognathia.