ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

【Objective】 To form the sampling data interval by retrospectively analyzing the sampling data of quality monitoring of fresh frozen plasma, cryoprecipitates and leukocyte-free platelets in all blood stations in Hebei Province during the past 7 years. 【Methods】 The data of blood component sampling from 12 blood station quality control laboratories in Hebei from 2015 to 2021 were collected. The FⅧ content and plasma protein content of fresh frozen plasma, the FⅧ content and fibrinogen content of cryoprecipitates, and the leukocyte residuals, red blood cell mixed and platelet content of leukocyte-free platelets were taken as the objects for discrete point and fitted curve analysis. 【Results】 The FⅧ level of fresh frozen plasma: (1.36±1.1) IU/mL, 5 blood stations showed a representative overall high or low or fluctuated characteristics; Fresh frozen plasm-plasma protein items: overall mean ±SD: (61.13±16.7) g/L, four blood stations showed scattered distribution or continuous high value scattered points; Cryoprecipitates FⅧ: the overall mean ±SD: (134.25±58.7) IU/mL, four blood stations showed the differentiation characteristics of continuous high, low or stable in the middle; Cryoprecipitates-fibrinogen items: the overall mean ±SD: (215.27±83.5) mg, five blood stations showed the overall high or low and fluctuated. Leukocyte-free apheresis platelet-to-leukocyte residual items: overall mean ±SD: 0.37±0.96 (×10⁶/bag), two blood stations showed a relatively high representative overall characteristics, and the rest were concentrated between 0 and 1; The total mean ±SD of platelet-to-red blood cell mixture without leukocyte was 2.45±2.82 (×10⁹/bag), with obvious segmented concentrated distribution, and scattered distribution in 3 blood centers. Platelet content: the overall mean ±SD was 3.14±1.55 (×10¹¹/bag), many deviations were noticed in 3 blood stations, and 1 blood station showed representative overall high characteristics. 【Conclusion】 This analysis shows that the distribution status of each blood station in different items is similar. The distribution status of discrete point groups and the change trend of the concentrated part of the fitting curve show that there are some differences in the monitoring level between the quality control laboratories of each blood station, and the update of detection instruments and reagents and the selection of detection methods greatly affect the test results. The summary data presented the index interval framework formed in the past 7 years, which helped to understand the difference between the results of each laboratory, correct the accuracy of the test results, better play the guiding role of quality monitoring in the blood preparation process, and continue to enhance the standardization of the whole process of blood collection and supply in the province.

Objective:To explore the application of transbronchial lung cryobiopsy guided by endobronchial ultrasound sheath (EBUS-GS-TBCB) in diagnosis of nonresolving pneumonias.Methods:Sixty patients with nonresolving pneumonias from March 2019 to July 2020 in Dalian Municipal Central Hospital were selected. The patients were divided into EBUS-GS-TBCB group (31 cases) and transbronchial forcep lung biopsy guided by endobronchial ultrasound sheath(EBUS-GS-TBLB) group (29 cases) by random digits table method.Results:The diagnostic rate of nonresolving pneumonias in EBUS-GS-TBCB group was significantly higher than that in EBUS-GS-TBLB group: 87.10% (27/31) vs. 65.52% (19/29), and there was statistical difference ( χ2 = 3.90, P = 0.048). There were no statistical difference in sensitivity, specificity, accuracy, positive predictive value and negative predictive value between 2 groups ( P>0.05). There were no statistical difference inthe shortest distance from lesions to pleura, incidence of pneumothorax and incidence of bleeding between EBUS-GS-TBCB group and EBUS-GS-TBLB group: (27.42 ± 2.88) mm vs. (27.01 ± 2.37) mm, 6.45%(2/31) vs. 3.45%(1/29) and 22.58%(7/31) vs. 13.79% (4/29), P>0.05. Among the causes of nonresolving pneumonias, infectious factors accounted for 21.67% (13/60), non infectious factors accounted for 66.67% (40/60), and uncertain causes accounted for 11.67% (7/60). Conclusions:The diagnostic rate of EBUS-GS-TBCB in nonresolving pneumonias is significantly higher than EBUS-GS-TBLB, and the complications such as bleeding and pneumothorax do not increase significantly.

Objective:To investigate the effect of transcranial direct current stimulation (tDCS) on the behavior and the mismatch negativity (MMN) component of the auditory evoked potential of autistic children.Methods:Thirty-four autistic children were randomly divided into an anode stimulation group ( n=19) and a pseudo-stimulation group ( n=16). Both groups were given one hour of routine rehabilitation five times a week for 4 weeks, while the anode stimulation group was additionally provided with 20 minutes of tDCS 3 times a week. Before and after the treatment, both groups′ behavior was evaluated by using autism behavior checklist (ABC) as well as any changes in MMN of the auditory evoked EEG signals. Results:There were no significant differences between the two groups in any of the measurements before the treatment. Afterwards behavior had improved significantly in both groups, with significantly greater improvement in the stimulated group. In the stimulated group the average MMN amplitude had increased significantly and the average latency had decreased significantly. However, no such significant changes were observed in the pseudo-stimulation group. There was a significant linear correlation between the changes in the incubation period of MMN components and the improvements in ABC, vestibular functioning, tactile defense and proprioception.Conclusion:Anodal tDCS combined with conventional rehabilitation therapy can effectively increase the MMN amplitude and shorten the latency in autistic children, improving their brain function.

Objective:To investigate the risk factors of lymph node metastasis and the clinical significance of deep submucosal invasion in patients with T1 stage colorectal cancer.Methods:From January 30, 2010 to December 31, 2019, at Shandong Provincial Hospital Affiliated to Shandong First Medical University, among patients with T1 stage colorectal cancer, 41 patients underwent radical surgery for colorectal cancer (surgery group) and 23 patients received endoscopic submucosal dissection (ESD) (ESD group) were enrolled. The tumor gross type, maximum diameter, histologically poorly differentiated components, degree of invasion (the type of mucosal muscle destruction, the width and depth of invasion), the budding grade of tumor, and whether with vascular tumor thrombus were recorded. The additional treatment and prognosis of patients were collected by telephone follow-up. The risk factors of lymph node metastasis in stage T1 colorectal cancer, the correlation between the complete muscularis mucosa destruction and the width and depth of invasion in the ESD group, and the effects of additional treatment after operation on the prognosis of patients were analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The rate of lymph node metastasis in patients with poorly differentiated components or vascular tumor thrombus was higher than that in patients without poorly differentiated components or vascular tumor thrombus (3/6 vs. 12.1%, 7/58; 3/4 vs. 11.7%, 7/60), and the differences were statistically significant ( χ2=5.934 and 11.409, both P<0.05). All patients in the surgery group had complete muscularis mucosa destruction. In ESD group, the width of tumor invasion was ≥ 2 mm in 16 cases, including complete destruction of muscularis mucosa in 15 cases and partial destruction in one case; the width of tumor invasion was <2 mm in seven cases, including complete destruction of muscularis mucoa in two cases and partial destruction in five cases; the depth of infiltration was ≥ 2 000 μm in 14 cases, including complete destruction of muscularis mucosa in 13 cases and partial destruction in one case; the depth of infiltration was <2 000 μm in nine cases, including complete destruction of muscularis mucosa in four cases and partial destruction in five cases. The complete muscularis mucosa destruction was related with tumor of invasion width ≥ 2 mm and invasion depth ≥ 2 000 μm (15/16 vs.2/7, 13/14 vs. 4/7), and the differences were statistically significant ( χ2=10.729, 6.659, both P<0.05). Among the 64 patients with T1 stage colorectal cancer in this study, six cases (9.4%) had poor prognosis; five cases (7.8%) died, and three of them (4.7%) were tumor-related deaths. Adjuvant therapy was added in 10 cases in surgery group and 10 cases in ESD group, and there were no poor prognosis in those patients. There were no significant difference in the incidences of poor prognosis of patients without additional treatment and patients with additional treatment of the two groups (9.7% (3/31) vs. 0 (0/10) and 23.1% (3/13) vs. 0 (0/10)) (both P>0.05). Conclusion:When T1 stage colorectal cancer with tumor submucosal invasion, clinicians should comprehensively evaluate the prognostic risk based on various pathological characteristics such as the degree of tumor differentiation, vascular tumor thrombus and mucosal muscle destruction.

Objective:To investigate the epidemiological characteristics and transmission chain of COVID-19 in two families, and to provide scientific evidence for effective prevention and control measures.Methods:Field epidemiological investigation was conducted for the COVID-19 cases occurred in two families and the close contacts in a county of Baotou city in Inner Mongolia Autonomous Region. Descriptive statistical analysis on epidemiological data was conducted.Results:The infection source of the COVID-19 cases in the two families was a man who had living history in Wuhan. After his return, his parents were infected by him. A few days later, the members of a neighbor family were found to be infected, and relatives of this family were also infected after dining together repeatedly. Finally, ten confirmed cases and three suspected cases of COVID-19 were detected in the two families.Conclusions:Human-to-human transmission of COVID-19 can occur not only in a family but also in neighborhoods. The cases in two families had close relationship, indicating the necessity to strengthen the health education about COVID-19 prevention and control and the management of groups at high risk to reduce the incidence of COVID-19 in families and neighborhoods.

Objective: To investigate the role of des-gamma-carboxy prothrombin (DCP) in assessment of liver function and prognosis of patients with liver cirrhosis. Methods: From January 2013 to August 2016, a total of 137 patients with liver cirrhosis in Shanghai Changzheng Hospital were enrolled. The serum DCP level was measured, the clinical data was collected and the complication and survival situation was followed up. The 137 patients were divided into DCP negative group (DCP≤40 mAU/mL, 118 cases) and DCP positive group (DCP>40 mAU/mL, 19 cases). Forty-five patients with compensated liver cirrhosis were divided into high-level DCP group (DCP>16.5 mAU/mL, 32 cases) and low-level DCP group (DCP≤16.5 mAU/mL, 13 cases). Chi square test was used to analyze the difference in the positive rate of DCP in patients with different Child-Pugh classification. Spearman correlation test was performed to analyze the correlation between DCP and model for end-stage liver disease (MELD) scores. Kaplan-Meier survival curve was used to analyze the correlation between DCP and liver disease related mortality. Results: Compared to that of DCP negative group, albumin level of patients in DCP positive group decreased (35 g/L, 20 to 57 g/L vs. 29 g/L, 17 to 42 g/L), however, total bilirubin (TBil), prothrombin time (PT), and international normalized ratio all increased (12.9 mg/L, 1.80 to 83.0 mg/L vs.22.2 mg/L, 6.4 to 169.0 mg/L; 15.5 s, 11.7 to 35.7 s vs.17.5 s, 13.9 to 33.4 s; 1.24, 0.96 to 3.72 vs.1.44, 1.09 to 3.22), and the differences were statistically significant (Z=-2.785, -2.891, -2.945 and -2.879, all P<0.01). The DCP positive (DCP>40 mAU/mL) rates of Child-Pugh A, B and C patients were 1.8% (1/55), 21.2% (11/52) and 23.3% (7/30), respectively, and the difference was statistically significant (χ²=11.246, P=0.003). The DCP levels of patients with Child-Pugh class B and C cirrhosis were significantly correlated with MELD scores (r=0.259, P=0.021). There were 16 and three patients with ascites and spontaneous bacterial peritonitis (SBP) of DCP positive group, and the incidence was higher than that of DCP negative group (55.1%, 65/118 and 1.7%, 2/118), and the differences were statistically significant (χ²=5.744 and 97.636, both P<0.05). Patients in high-level DCP group had a higher proportion of clinical decompensation than low-level DCP group (53.1% (17/32) and two cases), the difference was statistically significant (χ²=5.397, P=0.024). The overall survival rate of DCP positive group (nine survival cases) were lower than that of DCP negative group (87.9%, 87/99), and the difference was statistically significant (χ²=5.442, P=0.020). Conclusions Serum DCP level is closely related to liver function, ascites and SBP in patients with liver cirrhosis. Furthermore, it is associated with occurrence of decompensation in compensated patients and liver-related mortality in patients with liver cirrhosis. DCP may be a useful serum marker for evaluation of disease severity and prognosis in patients with liver cirrhosis in clinical practice.

Objective To investigate dynamic changes of serum Tau proteins and their correlation with cognitive dysfunction in patients with acute traumatic brain injury (TBI).Methods A total of 95 patients with acute TBI were retrospectively studied by case-control study.There were 61 males and 34 females,with age of 16-65 years [(40.7 ± 13.6)years].The Glasgow coma scale (GCS) was 3-8 points in 9 patients,9-12 points in 11,and 13-15 points in 75.A total of 30 healthy physical examinees were recruited as control group.The levels of Tau proteins were measured at days 1,3,5,7 and 14 after TBI.The cognitive dysfunction was evaluated by the Montreal Cognitive Assessment (MoCA) score at 6 months after injury.The correlation between Tau protein levels at different time points and MoCA was determined.Results The serum Tau proteins of TBI group was significantly higher than that of control group at all time points (P ＜ 0.05).In TBI group,39 (41％) out of 95 patients developed cognitive dysfunction assessed by MoCA scale.The main manifestations of cognitive dysfunction were the defects in visual spatial and acting function,delayed memory,language,abstract,attention and calculation,with statistical significance compared with control group (allP ＜ 0.05).The serum Tau proteins of patients with cognitive dysfunction were significantly higher than those without cognitive dysfunction at all time points after TBI (P ＜ 0.05).Tau proteins at days 1,3,5 after TBI was significantly correlated with cognitive dysfunction at 6 months after TBI (P ＜ 0.05).Conclusions The levels of serum Tau proteins show a significant increase after TBI,the early changes of which are statistically related to cognitive dysfunction.The early changes of serum Tau protein after TBI can be used as a reliable biomarker for early prediction of cognitive function prognosis.

Objective To investigate the clinical manifestations,pathological features,treatment and prognosis of nongesta-tional choriocarcinomas.Methods The clinicopathological data in 4 cases of nongestational choriocarcinoma were retrospectively analyzed and the relevant literatures were reviewed.Results All 4 patients had no confirmed diagnosis at first visit to hospital.All patients received the operative therapy and postoperative bleomycin,etoposide and cis-platinum (BEP)regimen chemotherapy.The followed up lasted for 3-32 months.One case died at postoperative 26 months due to pulmonary metastasis;one case was loss of follow up;two cases had relatively favorable condition.Conclusion Nongestational choriocarcinoma is a rare and highly invasive trophoblastic neoplasm,and is prone for early distant metastasis.The treatment is recommended to adopt operation combined with postoperative combined chemotherapy of multiple drugs.

BACKGROUND: Carbamylated erythropoietin (CEPO) cannot only remarkably promote the prognosis of cerebral infraction, but also improve the microcirculation. OBJECTIVE: To explore the underlying mechanism of CEPO promoting the microcirculation following cerebral infraction. METHODS: 150 Wistar rats were selected, and 120 rats were used for establishing the models of cerebral infarction, followed by allotted into four groups. The model rats were treated with 500, 1000 and 2000 u/kg CEPO as experimental groups, and those received no treatment as model group. The other 30 rats were as controls. Vascular endothelial cells were isolated and cultured in vitro, and the cell proliferation was detected by cell counting kit-8 assay. The expression levels of proliferation-related genes (Ki67 and p16) and vascular endothelial growth factor (VEGF) were detected using western blot assay. After selective silencing of VEGF through RNA interference, all above indicators were detected again. RESULTS AND CONCLUSION: Cell counting kit-8 assay results showed that the proliferation ability of vascular endothelial cells was increased with CEPO concentration increasing. Western blot assay results showed a significant upregulation of Ki67, p16 and VEGF. After shRNA-VEFG interference, these indicators had no positive correlation with the increased concentration of CEPO. Our findings indicate that CEPO can improve the proliferation of vascular endothelial cells in an animal model of cerebral infarction via upregulating the VEGF expression.