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.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective:To study the effects of sacubitril valsartan sodium on vascular sclerosis and ventricular remodeling in patients with ischemic cardiomyopathical coronary heart disease.Methods:A prospective research method was adopted. One hundred and eighty-six patients with coronary heart disease who were treated in Hangzhou Ninth People′s Hospital from January to December 2021 were selected and divided into control group and observation group by random digits table method, with 93 cases in each group. The control group adopted routine treatment method of aspirin + metoprolol + nitroglycerin + captopril according to the guideline, while the observation group was additionally treated with sacubitril valsartan sodium on the basis of the control group. The clinical efficacy, vascular endothelial function and hardness, cardiac function, ventricular remodeling and adverse reactions were compared between the two groups.Results:The total effective rate of treatment in observation group was significantly higher than that in control group: 96.77%(90/93) vs. 87.10%(81/93), and there was statistical difference ( P<0.05). After treatment, the brachial artery flow-mediated dilation in observation group was significantly higher than that in control group: (14.46 ± 2.80)% vs. (13.09 ± 2.74)%, the level of endothelin-1 was significantly lower than that in control group: (73.32 ± 9.63) ng/L vs. (77.47 ± 10.35) ng/L, and there were statistical differences ( P<0.05). After treatment, the left ventricular ejection fraction (LVEF) in observation group was significantly higher than that in control group: (50.87 ± 3.52)% vs. (49.72 ± 3.71)%, the left ventricular end-systolic diameter, left ventricular end-diastolic diameter and ventricular remodeling indicators of interventricular septal thickness and left ventricular mass index were significantly lower than those in control group: (38.26 ± 5.18) mm vs. (40.05 ± 5.20) mm, (50.49 ± 4.33) mm vs. (52.08 ± 4.25) mm, (8.95 ± 0.39) mm vs. (9.08 ± 0.41) mm, (118.49 ± 9.58) g/m 2 vs. (121.58 ± 9.62) g/m 2, and there were statistical differences ( P<0.05). There were no statistical differences in the levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol after treatment between the two groups ( P>0.05). There were no statistical differences in the incidences of adverse reactions between the two groups ( P>0.05). Conclusions:Sacubitril valsartan sodium has a good clinical efficacy in the treatment of coronary heart disease, and it can improve cardiac function and vascular sclerosis and reverse ventricular remodeling. In addition, it has no significant adverse reactions and is conducive to disease recovery.

Objective:To study the personality development of obsessive-compulsive disorder (OCD) from the perspective of memory-tracing.Methods:From January 2016 to May 2017, totally 103 patients with OCD (patient group) and 88 normal subjects (control group) matched with age, gender, and educational level in the national urban population norm database of Wang Weidong memory-tracing personality developmental inventory (WMPI) were included.WMPI was used to evaluate and compare all subjects.SPSS 22.0 software and nonparametric test were used for statistically analysis, and independent sample t-test and nonparametric test were used for data camparison. Results:1.In terms of external influencing factors of personality development: on the part of life events, the score of family affair in the patient group was higher than that in the control group( P<0.05) in childhood.In terms of upbringing, the scores of strictness (5.637±3.463) and punishment (6.275±4.565) in the patient group were higher than those ((4.341±3.092), (5.000±3.698)) in the control group in childhood( t=-2.703, -2.093, both P<0.05). 2.In the aspect of personality elements: (1) Among courage subscales, the scores of natural fear (7.686±3.441) and adaptability (15.000±5.321) in the patient group were higher than those((6.023±3.991), (12.841±6.070)) in the control group in childhood ( t=-3.085, -2.613, both P<0.05) .For all three stages, interpersonal fear scores in the patient group ((20.284±8.255), (22.804±7.458), (22.725±7.145))were all higher than those ((16.205±7.937), (19.841±6.319), (18.364±6.277))in the control group( t=-3.458, -2.929, -4.437, P<0.01). (2) Among interpersonal relationship, the dependence dimension scores were higher in the patient group (10.804±3.621) than those (8.830±4.850) in the control group during childhood( t=-3.205, P<0.01). (3) Among sex development, the scores of heterosexual communications (11.941±4.878), love concept (15.098±4.180) and sexual concept (8.892±2.988) were higher in the patient group than those ((9.125±5.040), (11.761±5.202), (6.943±3.288)) in the control group in adolescence(all P<0.01). (4) Among ego, the score of self-care dimension in the patient group (6.465±2.890) was higher than that in the control group(4.239±2.861) in childhood ( P<0.01). In the dimension of autonomy, the scores of the patient group ((10.772±2.694), (11.347±2.621)) were higher than those in the control group ((8.011±4.039), (9.818±2.693)) in childhood and adolescence (both P<0.01). (5) Among the way of thinking, the score of absolute thinking dimension in the patient group was higher than that in control group in childhood ( P<0.01). In the dimension of cautious, the scores of patient group were higher than those in the control group in childhood and adolescence (both P<0.01). (6)Among volition, the scores of decisive dimension in the patient group were higher than those in the control group in adolescence and youth (both P<0.01). In the dimension of consciousness, the score of patient group was higher than that in the control group in youth( P<0.01). In the dimension of insistence, the score of the patient group were higher than those in the control group in childhood and youth (both P<0.01). (7) Among worldviews, the scores of motivations, perspective of career and perspective of friendship in the patient group were higher than those in the control group in adolescence (all P<0.01). The score of value dimension in patient group was lower than that in the control group in the youth ( P<0.01). Conclusion:Patients with OCD have more strictness and punishment during their childhood in terms of upbringing.This leads to a lack of courage, poor interpersonal relationships, low self-care or autonomy, high attachment, absolutization of thinking and suppressing themself more in their childhood.In their adolescence and youth, their lack of courage, poor self-care or autonomy and the way of thinking cautious and stubborn will further aggravate and gradually show a more conservative sexual development and traditional world outlook.

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 investigate the prenatal diagnosis and genetic counseling of fetal nuchal fold (NF) thickening.Methods This study retrospectively analyzed 17 fetuses with increased NF detected by prenatal ultrasound examination in Peking Union Medical College Hospital,Peking Union Medical College & Chinese Academy of Medical Sciences from December 1,2016 to December 1,2017.All cases were divided into isolated (isolated group) or non-isolated increased NF group (non-isolated group) according to whether the fetus had concomitant ultrasonographic abnormalities or not.Karyotype and chromosomal microarray analysis (CMA) were performed on all cases.Clinical data,prenatal genetic testing results and pregnancy outcomes were analyzed.Results Of those twelve cases in the isolated group,two were terminated due to the identification of chromosomal abnormalities and pathogenic copy number variations (CNVs) and the fetal autopsy results were consistent with the prenatal diagnosis.The rest 10 pregnancies were all continued including one fetus carrying a variant of unknown significance,which was proved to be a paternal heredity by CMA,and nine without genetic abnormalities and all-these infants were healthy during follow-up.Among the five non-isolated cases,one was diagnosed as trisomy 21 by karyotyping and CMA,and the other four were found to have structural abnormalities under ultrasound scan,but without genetic abnormalities in karyotyping and CMA.And all the five pregnancies were terminated after genetic counseling and three of them chose whole exome sequencing (WES) for further test.One homozygous mutation in CHRNA 1 gene and one de novo mutation in SETD2 gene were found in two cases,respectively,while no abnormality was identified in the other one case.Conclusions Once increased NF were indicated by ultrasound examination,prenatal genetic testing should be offered to the patients,including CMA,regardless of other ultrasonographic abnormalities,and WES should also be offered when necessary.Considering a thickened NF is associated with increased risks of structural defects,a close follow-up with fetal echocardiography and ultrasound is required even the prenatal tests are normal.

Objective To investigate the relationship between prognostic nutritional index (PNI) and neutropenia after adjuvant chemotherapy in patients with colorectal cancer. Methods The clinical data of 44 patients with colorectal cancer performed adjuvant chemotherapy in Shunyi District Hospital from December 2014 to January 2018 were retrospectively analyzed, and the patients were divided into group A (grade 0-2 neutropenia) and group B (grade3-4 neutropenia) according to the degree of neutropenia. The serum albumin, peripheral lymphocyte counts, and neutrophil counts within 1 week before chemotherapy were collected, and the PNI was calculated. The chi-square test and rank sum test were used to compare the clinical data, body mass index (BMI), baseline neutrophil count, and PNI between the two groups. Logistic regression analysis was used to analyze the risk factors for neutropenia after chemotherapy. Results The baseline median neutrophil counts and median PNI in group A were 3.17×109/L [(1.38-7.79)×109/L] and 50.40 (37.40-57.05), and in group B were 2.54 ×109/L [(1.22-3.87) ×109/L] and 45.50 (37.95-50.95). The baseline neutrophil counts and PNI in group A were significantly higher than those in group B, the differences between the two groups were statistically significant (Z= -2.085, P= 0.037; Z= -2.615, P= 0.009). Logistic regression analysis showed that PNI was an independent risk factor for neutropenia after chemotherapy (HR=0.803, 95％CI 0.646-0.998, P= 0.048). Conclusion PNI has a certain role in predicting neutropenia after adjuvant chemotherapy in patients with colorectal cancer.

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 cognitive status of medical students of a medical university on laboratory biosafety,and provide basic data for laboratory biosafety management in Chinese universities.Methods 900 full-time undergraduate medical students were chosen by cluster random sampling,questionnaires were filled out in by them.Results 900 questionnaires were distributed,877 (98.21％) valid questionnaires were obtained,49.03％ (n =430) were from sophomores,50.97 ％ (n =447) from juniors,148 (16.88 ％) students have ever participated in students'scientific research.The overall awareness rate of laboratory biosafety was 58.72％,only 32.16％ of students understood the detailed contents of laboratory biosafety regulations,only 8.21％ of students have received training in laboratory biosafety;the awareness rate of laboratory biosafety cabinet was only 14.14％,only 7.75％ of students knew which operation should be performed in biosafety cabinet;28.28％ of students could deal with waste according to the rules,68.19％ of students were able to identify warning signs of biological hazard;92.82％ of the students thought that laboratory biosafety-related courses should be set up.The overall awareness rate of laboratory biosafety knowledge and safety behavior was low,which were 42.65％ and 41.96％ respectively,juniors was higher than that of sophomores(P＜0.05);in the aspect of chemical hazards and biological hazards,students with scientific research experience scored higher than those who did not participate in scientific research(all P＜0.05).Conclusion Medical students' cognition on knowledge of laboratory biosafety is not optimistic,it is imperative to strengthen the management of education and publicity of laboratory biosafety.

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.