[CD44 regulates biological behavior and Ras signaling pathway in nasopharyngeal carcinoma stem cells].

Objective: To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44. Methods: CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44. Results: The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation (P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively(P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 (P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F (P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells (P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells (P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells(r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) (P<0.01). Conclusions: Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.

[Changes of electroencephalography power spectrum during joint position perception test after anterior cruciate ligament rupture].

OBJECTIVE: To measure the electroencephalography (EEG) of the patients with anterior cruciate ligament (ACL) rupture when performing joint position perception movement task, to compare the differences between the ACL rupture side and the unaffected side, to identify the EEG change in the power spectrum caused by the ACL rupture, and to provide evidence for the diagnosis, treatment and rehabi-litation for ACL injury as well as knee instability. METHODS: Sixteen male patients, selected from the Department of Sports Medicine, Peking University Third Hospital from November 2014 to April 2015, with only ACL rupture on one side used isokinetic muscle strength testing equipment were enrolled in the study to perform unilateral active knee joint positional movement and passive knee joint positional movement tasks. EEG was recorded to compare between the affected and unaffected limb of ACL rupture patients when doing single leg movement tasks, including passive knee joint position test and active knee joint position sensation test. The target position of the active knee joint position movement task and the passive knee joint position movement task was 30 degrees of knee flexion. RESULTS: During the passive knee joint position test, there was no significant difference in EEG power spectrum of Delta[F (1, 15)=0.003, P=0.957, ηP2 =0.001], Theta[F (1, 15)=0.002, P=0.962, ηP2 < 0.001], Alpha[F (1, 15)=0.002, P=0.966, ηP2 =0.001], Beta[F (1, 15)=0.008, P=0.929, ηP2 =0.001] at Fz, Cz, and Pz between the affected and unaffected limbs in the ACL patients. During the active knee joint position movement task, the EEG power spectrum of Delta, Theta, Alpha, Beta at Fz and Cz location, on the affected side was significant higher than on the unaffected side. CONCLUSION: This study compared the differences between the ACL rupture side and the unaffected side during active knee position movement task and passive knee position movement task, and identifyied the EEG changes in the power spectrum caused by the ACL rupture, It was found that the central changes caused by unilateral ACL rupture still existed during contralateral (unaffected) side movement. The EEG power spectrum of the affected side during active exercise was significantly higher than that of the unaffected side This study provides new electrophysiological evidence for the study of ACL injury.

[Effects of visual restoration on dynamic plantar pressure features in elder individuals].

OBJECTIVE: To analyze the effects of visual restoration after cataract surgery on plantar pressure and biomechanics of foot in elder individuals. METHODS: Thirty-two patients [male/female 5/27, (70.1±5.2) years old] with age-related cataract were recruited between October 2016 and December 2019. The footscan system was employed to record the data of plantar pressure during level walking before and 1-month after the cataract surgery. Parameters of peak pressure (PP), impulse (I), pressure-time integral (PTI) and time to peak pressure (TPP) from the regions of the 1st toe (T1), 2nd to 5th toes (T2-5), 1st to 5th metatarsal heads (M1-M5), midfoot (MF), medial hindfoot (HM) and lateral hindfoot (HL) were analyzed respectively. RESULTS: Post-operatively, the visual function was effectively reconstructed with improved visual acuity in both eyes (Z=-4.878, -4.801; P < 0.001). The PP (t=2.266, P=0.031) and I (t=2.152, P=0.039) values in M2 region on the dominant side (right foot) increased statistically at post-operative phase, while the changes of pressure and temporal para-meters in other regions remained stable. There was laterality in plantar pressure at pre-operative phase, manifested as greater PP values in M1, M2, MF, and HM regions on the dominant sides (t=-2.414, -2.478, -2.144, -5.269; P < 0.05), greater PP values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.830, 3.155, 2.686, 3.683; P < 0.05), greater I values in M1, MF, and HM regions on the dominant sides (t=-2.380, -2.185, -5.320; P < 0.05) and greater I values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.489, 2.247, 2.838, 3.992; P < 0.05). post-operatively, the pressure tended to be compatible between the two sides in regions of M3 and MF, while the magnitude of laterality in regions of M1 (ZPP△= -2.721, P=0.007; ZI△=-2.581, P=0.010), M2 (ZPP△=-2.674, P=0.007; ZI△=-2.375, P=0.018) and M5 (ZPP△=1.991, P=0.046; ZI△=2.150, P=0.032) was further increased. CONCLUSION: Changes in plantar pressure after cataract surgery were characterized as increased pressure in the 2nd metatarsal head area on the dominant side. Visual restoration might intensify the laterality in the medial of forefoot on the dominant side and the lateral of forefoot on the non-dominant side.

[Finite element analysis of the graft stresses after anterior cruciate ligament reconstruction].

OBJECTIVE: To explore the stress distribution characteristics of the graft after anterior cruciate ligament (ACL) reconstruction, so as to provide theoretical reference for the surgical plan of ACL reconstruction. METHODS: Based on 3D MRI and CT images, finite element models of the uninjured knee joint and knee joint after ACL reconstruction were established in this study. The uninjured knee model included femur, tibia, fibula, medial collateral ligament, lateral collateral ligament, ACL and posterior cruciate ligament. The ACL reconstruction knee model included femur, tibia, fibula, medial collateral ligament, lateral collateral ligament, ACL graft and posterior cruciate ligament. Linear elastic material properties were used for both the uninjured and ACL reconstruction models. The elastic modulus of bone tissue was set as 17 GPa and Poisson' s ratio was 0.36. The material properties of ligament tissue and graft were set as elastic modulus 390 MPa and Poisson's ratio 0.4. The femur was fixed as the boundary condition, and the tibia anterior tension of 134 N was applied as the loading condition. The stress states of the ACL of the intact joint and the ACL graft after reconstruction were solved and analyzed, including tension, pressure, shear force and von Mises stress. RESULTS: The maximum compressive stress (6.34 MPa), von Mises stress (5.9 MPa) and shear stress (1.83 MPa) of the reconstructed ACL graft were all at the anterior femoral end. It was consistent with the position of maximum compressive stress (8.77 MPa), von Mises stress (8.88 MPa) and shear stress (3.44 MPa) in the ACL of the intact knee joint. The maximum tensile stress of the graft also appeared at the femoral end, but at the posterior side, which was consistent with the position of the maximum tensile stress of ACL of the uninjured knee joint. More-over, the maximum tensile stress of the graft was only 0.88 MPa, which was less than 2.56 MPa of ACL of the uninjured knee joint. CONCLUSION: The maximum compressive stress, von Mises stress and shear stress of the ACL graft are located in the anterior femoral end, and the maximum tensile stress is located in the posterior femoral end, which is consistent with the position of the maximum tensile stress of the ACL of the uninjured knee joint. The anterior part of ACL and the graft bore higher stresses than the posterior part, which is consistent with the biomechanical characteristics of ACL.

[A multicenter, randomized, double-masked, placebo-controlled trial of compound wild chrysanthemum eye masks for mild and moderate dry eye].

Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer Ⅰ test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer Ⅰ test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).

Oxymatrine therapy inhibited epidermal cell proliferation and apoptosis in severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic skin disorder that manifests as epidermal keratinocyte hyperplasia. OBJECTIVES: We examined the effect of oxymatrine treatment on cell proliferation and apoptosis in skin lesions of psoriasis. PATIENTS AND METHODS: Patients with severe plaque psoriasis were treated with oxymatrine or with acitretin. The skin lesions were stained with proliferating cell nuclear antigen (PCNA), Ki-67 and Bcl-2, as well as examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). We performed correlations of the Psoriasis Area and Severity Index (PASI) and the proliferation and apoptosis index. RESULTS: Oxymatrine significantly reduced the psoriasis lesions as demonstrated by the reduced PASI score after treatment [6·91; 95% confidence interval (CI) 5·00-8·81, P < 0·001]. In the oxymatrine group, the mitotic index was 26·15 (95% CI 24·80-27·49) before oxymatrine treatment, decreasing to 14·52 (95% CI 13·82-15·25; P < 0·001) after treatment, but remained higher than the normal group (6·24; 95% CI 5·87-6·61, P < 0·001). Oxymatrine also inhibited the proliferation of epidermal cells in the skin lesion as indicated by the reduced proliferation index after treatment (P < 0·01). In addition, oxymatrine treatment reduced cellular apoptosis as shown by increased Bcl-2 expression and a decrease in TUNEL-positive cells. The PASI score was positively correlated with mitotic index, proliferation index and apoptotic index (TUNEL), but negatively correlated with Bcl-2 expression. CONCLUSIONS: Oxymatrine treatment reduced proliferation but inhibited apoptosis of cells in the skin lesion. The balance between cell proliferation and turnover may contribute to the significant alleviation of psoriasis by oxymatrine. What's already known about this topic? Psoriasis manifests as epidermal keratinocyte hyperplasia with proliferation, keratinocyte maturation and turnover rates. Current drugs for psoriasis may inhibit cell proliferation but could not adjust the balance of cell division, differentiation and apoptosis. What does this study add? We studied the efficacy of oxymatrine in the treatment of psoriasis and analysed the correlation of skin lesions, proliferation and apoptosis index before and after oxymatrine treatment. What is the translational message? Our study has demonstrated that oxymatrine is effective in the treatment of severe plaque psoriasis. It has comparable efficacy with acitretin. Because acitretin treatment was sometimes associated with metabolic abnormalities, our study suggests oxymatrine therapy as an alternative treatment for psoriasis in the context of acitretin allergy or adverse reactions.

Electronic nematicity above the structural and superconducting transition in BaFe2(As(1-x)P(x))2.

Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice, has been observed in the iron pnictide and copper oxide high-temperature superconductors. Whether nematicity plays an equally important role in these two systems is highly controversial. In iron pnictides, the nematicity has usually been associated with the tetragonal-to-orthorhombic structural transition at temperature T(s). Although recent experiments have provided hints of nematicity, they were performed either in the low-temperature orthorhombic phase or in the tetragonal phase under uniaxial strain, both of which break the 90° rotational C(4) symmetry. Therefore, the question remains open whether the nematicity can exist above T(s) without an external driving force. Here we report magnetic torque measurements of the isovalent-doping system BaFe(2)(As(1-x)P(x))(2), showing that the nematicity develops well above T(s) and, moreover, persists to the non-magnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides. By combining these results with synchrotron X-ray measurements, we identify two distinct temperatures-one at T*, signifying a true nematic transition, and the other at T(s) (

DNA hydroxymethylation rate in the AChE and HoxC4 promoter associated with human sperm quality.

The relationship of altered DNA 5'-hydroxymethylation in human spermatozoa with seminal parameters remains unclear. The aim of the study was to investigate the association between the 5'-hydroxymethylcytosine (5hmC) rate in the promoters of acetylcholinesterase (AChE) and homeobox C4 (HoxC4) genes and human sperm concentration/motility. The study population consisted of three groups: asthenozoospermia (AZ), oligoasthenozoospermia (OAZ) and normozoospermia (NZ). The 5hmC rate in the promoter was measured by CCGG loci-dependent MspI/HpaII restriction mapping of glycosylation-modified sperm DNA combined with a hydroxymethylation-specific real-time polymerase chain reaction assay. The 5hmC rate in the AChE promoter in group AZ and OAZ was higher than that in group NZ (p < .05). A weak inverse correlation between 5hmC rate of AChE and sperm motility was observed in all subjects (r = -.172, p < .05). The 5hmC rate in the HoxC4 promoter in group OAZ was lower than that in group NZ (p < .05). These results indicated that altered 5hmC rates of AChE and HoxC4 promoters are associated with low sperm motility and sperm concentration respectively.

[Role of signaling pathway of long non-coding RNA growth arrest-specific transcript 5/microRNA-200c-3p/angiotensin converting enzyme 2 in the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome].

Objective: To investigate whether long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5)/microRNA-200c-3p/angiotensin converting enzyme 2(ACE2) involved in the regulation of the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome (ARDS). Methods: ARDS rat models were established and were divided into control, ARDS, ARDS+ pcDNA and ARDS+ pcDNA-GAS5 groups. Six hours after the establishment of ARDS rat model, arterial blood and lung tissues of the rats from the four groups were collected. The changes of partial pressure of oxygen (PO(2)) and partial pressure of CO(2) (PCO(2)) were analyzed and the expression of GAS5 in lung tissue was observed in these groups. Then, A549 cells were divided into control, lipopolysaccharide (LPS), LPS+ pcDNA, LPS+ pcDNA-GAS5, LPS+ pcDNA-GAS5+ pre-NC, LPS+ pcDNA-GAS5+ miR-200c-3p mimic groups. Quantitative real-time PCR (qRT-PCR) was conducted to measure lncRNA GAS5, ACE2 and miR-200c-3p levels. RNA immunoprecipitation and RNA pull-down assay were used to detect the combination between GAS5 and miR-200c-3p. Western blotting was used to detect the protein level of ACE2. Flow cytometry was used to observe the apoptosis of A549 cells in those groups. The data between groups were compared by t test. Results: In ARDS rat model, PO(2) value was significantly increased in ARDS+ pcDNA-GAS5 group than that in ARDS+ pcDNA group[(81.5±3.3) vs (57.5±5.1) mmHg, t=4.850, P<0.05], and PCO(2) value was significantly decreased in ARDS+ pcDNA-GAS5 group than that in ARDS+ pcDNA group[(50.6±1.9) vs (64.0±1.9) mmHg, t=5.940, P<0.05]. LncRNA GAS5 level in A549 cells of LPS group decreased significantly than that in control group (0.43±0.01 vs 1.01±0.01, t=0.242, P<0.05). Compared with LPS+ pcDNA group, ACE2 expression increased significantly in LPS+ pcDNA-GAS5 group (0.85±0.04 vs 0.34±0.02, t=1.800, P<0.05). Compared with LPS+ pcDNA-GAS5+ pre-NC group, ACE2 expression decreased significantly in LPS+ pcDNA-GAS5+ miR-200c-3p mimic group (0.62±0.01 vs 0.84±0.02, t=9.440, P<0.05). Compared with control group, the percentage of A549 cell apoptosis promoted significantly in LPS group (25.90±0.61 vs 7.90±0.22, t=0.257, P<0.05). Compared with LPS+ pcDNA group, the percentage of A549 cell apoptosis suppressed significantly in LPS+ pcDNA-GAS5 group (10.50±0.37 vs 26.37±0.45, t=1.760, P<0.05). Compared with LPS+ pcDNA-GAS5+ pre-NC group, the percentage of A549 apoptosis promoted significantly in LPS+ pcDNA-GAS5+ miR-200c-3p mimic group (19.07±0.56 vs 10.87±0.26, t=0.643, P<0.05). Conclusion: In ARDS, down-regulation of lncRNA GAS5 decreases ACE2 expression through increasing miR-200c-3p to promote the apoptosis of A549 cells, thus to promote the progression of ARDS.

Efficacy of oxymatrine for treatment and relapse suppression of severe plaque psoriasis: results from a single-blinded randomized controlled clinical trial.

BACKGROUND: Drugs that are currently used in the treatment of psoriasis are associated with drawbacks such as rapid recrudescence, high costs and unwanted side-effects. Oxymatrine has a long history of clinical use in the treatment of hepatitis and cancer in China. OBJECTIVES: To explore the efficacy and safety of intravenous oxymatrine in patients with severe plaque psoriasis. METHODS: A total of 67 patients were randomly allocated to receive oxymatrine injections (0.6 g per day for 8 weeks) or acitretin capsules (0.75 mg kg-1 per day from week 0 to week 2 and 20-30 mg per day from week 3 to week 8) and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥ 50% reduction of Psoriasis Area and Severity Index (PASI 50) at week 32. The secondary end points included the skin classification grade and the Dermatology Quality of Life Index (DLQI) score. Side-effects were recorded throughout the whole study to assess the safety profile. RESULTS: Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P < 0.001), with no significant differences between the oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in the oxymatrine group was significantly lower than that of the acitretin group (P < 0.001). Moreover, while there was an increase in the number of patients with metabolic abnormalities in the acitretin group, a significant reduction was observed in the oxymatrine group. Furthermore, rates of adverse reactions were significantly decreased in the oxymatrine group compared with that of the acitretin group (P < 0.001). CONCLUSIONS: Treatment with oxymatrine effectively ameliorated severe plaque psoriasis, and was accompanied by only minor adverse effects.

Combined 3D-tomography and 3D-power Doppler for vascular imaging of the liver.

This study aimed to investigate the role of three-dimensional color tomographic ultrasound (3D-CTU) and three-dimensional color power Doppler (3D-CPD) imaging in diagnostics of liver lesions. Based on 3D-anatomical sectional structures of the liver, we used 3D-CTU and 3D-CPD techniques to reconstitute 3D-images of lobes, segments, and intra-segmental blood vessels, and lesions of the liver. With the use of this technique, we were able to generate 3D vascular patterns of liver lobes, segments and tumor lesions, and their spatial relationship. The observed vascular patterns of intra- and peri-tumor (including surrounding lobes and segments) and the spatial relation can be used for accurate positioning of liver lesions.

[The clinical characteristics of 346 patients with IgG4-related disease].

Objective: To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China. Methods: IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016. All patients were followed-up for more than 6 months. The demographic characteristics, symptoms, organ involvements, laboratory examinations and treatment efficacy were evaluated and analyzed. Results: A total of 346 patients were finally enrolled, including 230 males (66.5%) and 116 females (33.5%). The mean age of disease onset was (53.8±14.2) years old. The mostly common involved organs were lymph nodes (56.4%) and submandibular glands (52.6%). Other affected organs and manifestations included: swelling of the lacrimal glands (46.5%), autoimmune pancreatitis (38.4%), pulmonary involvement (28.0%), sclerosing cholangitis (25.4%), naso-sinusitis (23.4%), parotid gland swelling (21.7%), retroperitoneal fibrosis (19.9%), large arteries involvement (9.5%), kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9%), skin lesions (6.4%). Rare features consisted of thyroid glands, pituitary glands, gastrointestinal tract, pachymeningitis, pericardium, sclerosing mediastinitis and orchitis. The majority of patients had multi-organ involvement, such as 74.3% patients with 3 and more, 18.2% and 7.5% patients with 2 and single organ involvement respectively. The average IgG4-RD responder index (IgG4-RD RI) was 13.21±5.70. History of allergy was found in 172 (49.7%) patients. As to the laboratory tests, elevated serum IgG4 levels were confirmed in 285 (94.1%) patients, which was positively correlated with IgG4-RD RI. There were 33.5% patients receiving monotherapy of glucocorticoid, 52.6% treated with glucocorticoids combined with immunosuppressive agents, 4.9% patients with immunosuppressant only, and 9.0% patients with mild disease not receiving medication. The majority (336, 97.1%) patients improved the above regimens. Conclusion: IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement. The mostly common involved organs include lymph node, submandibular glands, and pancreas. Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

[Effect of prenatal stressful life event exposure on child emotional and behavioral problem at age 2-6 years].

Objective: To investigate the influence of prenatal stressful life event (SLE) exposure on child emotional and behavioral problem at age 2-6 years and identify the most risk exposure period. Methods: A total of 2 524 mother-child pairs were selected from Shanghai Maternal-Child Pairs Cohort based on pregnant women form 2016 to 2018 in Shanghai. Prenatal SLE exposure was assessed by Life Events Scale for Pregnant Women Questionnaire during the first and third trimester of pregnancy. Child emotional and behavioral problem was evaluated by Strengths and Difficulties Questionnaire at age 2-6 years. Multivariate binary logistic regression model and generalized estimating equation were conducted to quantify the association between prenatal SLE exposure and child emotional and behavioral problem at age 2-6 years, and identify the pregnancy period with strongest adverse effect. Results: The 2 524 mother-child pairs were divided into 4 groups: group with consistent low exposure to SLE (61.8%), group with high exposure to SLE in the first trimester (13.2%), group with high exposure to SLE in the third trimester (13.2%) and group with consistent high exposure to SLE (11.8%). The detection rates of emotional problem, hyperactivity, peer interaction problem and total difficulty score in children aged 3-6 years were highest in the group with consistent high exposure to SLE. Generalized estimating equation analysis showed that after controlling the confounding factors, compared with the consistent low exposure group, the children in the group with high exposure to SLE in the first trimester had significant increased risk for conduct problem at age 2-6 years (aOR=1.41, 95%CI:1.07-1.87). The children in the group with consistent high exposure to SLE were at increased risk for emotional problem, peer interaction problem, and high total difficulty score with the aOR of 1.41 (95%CI: 1.09-1.83), 1.46 (95%CI: 1.15-1.86) and 1.51(95%CI: 1.17-1.93). Conclusion: These findings indicated that prenatal exposure to SLE have adverse effect on child emotional and behavioral problem at age 2-6 years, especially the exposure in the first trimester.

Mutations in the ADAR1 gene in Chinese families with dyschromatosis symmetrica hereditaria.

We investigated 2 Chinese families with dyschromatosis symmetrica hereditaria (DSH) and search for mutations in the adenosine deaminase acting on RNA1 (ADAR1) gene in these 2 pedigrees. We performed a mutation analysis of the ADAR1 gene in 2 Chinese families with DSH and reviewed all articles published regarding ADAR1 mutations reported since 2003 by using PubMed. By direct sequencing, a 2-nucleotide AG deletion, 2099-2100delAG, was found in family 1, and a C→T mutation was identified at nucleotide 1420 that changed codon 474 from arginine to a translational termination codon in family 2. Two different pathogenic mutations were identified, c.2099-2100delAG and c.1420C>T, the former being a novel mutation, and the latter previously reported in 3 other families with DSH. To date, a total of 110 mutations in the ADAR1 gene have been reported, and 10 of them were recurrent; the mutations R474X, R1083C, R1096X, and R1155W might be the DSH-related hotspots.

[Comparative study on physical activity and its influencing factors in patients with chronic pulmonary obstructive disease between China and the United Kingdom].

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV1/FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate ORs and 95%CIs for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95%CI) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P<0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

[A qualitative systematic review and enlightenment of teaching models and evaluation in the general education of epidemiology in China and abroad].

Objective: This study aims to systematically sort out the effectiveness evaluation of the general education teaching models in epidemiology at home and abroad and provide a reference for the development and reform of epidemiology education. Methods: A systematic search of English databases such as PubMed, Embase, and Web of Science and Chinese databases such as CNKI, Sinomed, Wanfang, etc., were used to screen out the literature on different general teaching models of education in epidemiology. Each literature's teaching effect will be summarized and evaluated to conduct a systematic qualitative review in the narrative integration method, Results: A total of 45 articles (28 in Chinese and 17 in English) were included in this study, involving 14 teaching models, including mixed teaching models, PBL (problem-based learning), project designing models, and CBL (case-based learning) and other teaching models. Except for some teaching models such as project design, network platform, and flipped classroom model, the teaching effect of other innovative models is better than that of the traditional model. The distribution of teaching models was different in Chinese and foreign literature. Foreign teaching models were diverse, mainly concentrated in mixed teaching models and software/network platform learning. Domestic teaching models were relatively fixed. The mixed teaching model and PBL model were the most widely used in China, and there were fewer comparative studies between different teaching models than in foreign countries. Conclusion: General education in epidemiology is still in the early exploration stage. Compared with the traditional lecture model, the effect of various innovative teaching models has been improved. According to teaching objectives and student characteristics, we encourage extensive use of different teaching strategies, combining theoretical knowledge with practical applications and integrating epidemiological knowledge with inter-professional knowledge. Thus, students who can apply what they learn are becoming interdisciplinary talents our society needs.

Prognostic significance of age, sex, race, and socioeconomic status in patients with stage III-IV upper tract urothelial carcinoma.

OBJECTIVE: To assess the trend of incidence and survival stratified by age, race, gender and SES and the differences in time between groups in stage III-IV upper tract urothelial carcinoma (UTUC) patients. METHODS: 7,505 stage III-IV UTUC patients between 2004 and 2015 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The overall survival (OS) and the cancer-specific survival (CSS) rates were assessed using the Kaplan-Meier curve and log-rank test as well as multivariate Cox regression analysis. RESULTS: Among the 7,505 patients, 3,584 were classified as young, 2,464 were classified as middle-aged, and 1,461 were classified as elderly. The years of diagnosis were divided into three periods including 2004-2007, 2008-2011 and 2012-2015. The incidence rates for UTUC were 0.69, 0.74, and 0.77 per 100,000 in the first, second, and third period, respectively. Disparities in the long-term survival rate between male and female patients and among patients of different races narrowed over time. There was no difference in prognosis between races (p = 0.078 for OS and p = 0.167 for CSS). The difference in survival rate between the poor and rich groups narrowed along with the three time periods. CONCLUSIONS: Survival rate disparities according to sex, race, and socioeconomic status narrowed in time, except in patients aged 74-82 years. Increased age, black race, and poverty are associated with worse survival outcomes. In general, the long-term survival rate improved continuously across the three periods.

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta.

Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2. The severity of osteogenesis imperfecta varies, ranging from perinatal lethality to a very mild phenotype. Although there have been many reports of COL1A1 and COL1A2 mutations, few cases have been reported in Chinese people. We report on five unrelated families and three sporadic cases. The mutations were detected by PCR and direct sequencing. Four mutations in COL1A1 and one in COL1A2 were found, among which three mutations were previously unreported. The mutation rates of G>C at base 128 in intron 31 of the COL1A1 gene and G>A at base 162 in intron 30 of the COL1A2 gene were higher than normal. The patients' clinical characteristics with the same mutation were variable even in the same family. We conclude that mutations in COL1A1 and COL1A2 also have an important role in osteogenesis imperfecta in the Chinese population. As the Han Chinese people account for a quarter of the world's population, these new data contribute to the type I collagen mutation map.