Objective Establishment and evaluation of a mouse model of aldosterone-induced multi-organ damage.Methods Twenty mice were randomly divided into four groups,with five mice in each group:a blank control group(0 μg/(kg·d)),a low-dose aldosterone group(150 μg/(kg·d))),a medium-dose aldosterone group(300 μg/(kg d)),and a high-dose aldosterone group(450 pug/(kg·d)).Aldosterone-containing osmotic minipumps were surgically implanted under the skin,and aldosterone was infused for 4 weeks to establish the aldosterone-induced damage model.The body weight and blood pressure of the mice were recorded weekly.After the 4 week modeling period,the mice were euthanized,and their tissues were collected for observation and analysis of blood pressure and histological morphology of various organs.Results(1)After 4 weeks of aldosterone infusion,the serum aldosterone levels were significantly increased in the medium-dose and high-dose aldosterone groups,but not in the low-dose aldosterone group.(2)After the implantation of osmotic minipumps,the systolic blood pressure was significantly increased in the low-dose,medium-dose,and high-dose aldosterone groups during the second and third weeks,but decreased in all these groups during the fourth week.(3)The kidney and heart in the low-dose,medium-dose,and high-dose aldosterone groups showed varying degrees of damage,interstitial edema,collagen deposition,and fibrotic lesions.The liver in the low-dose aldosterone group showed a small amount of collagen deposition,while the medium-dose and high-dose aldosterone groups showed varying degrees of hepatocyte damage,collagen deposition,and fibrotic lesions.Conclusions Aldosterone can induce multi-organ damage in mice.Under this modeling method,organ damage is mainly manifested as edema,collagen deposition,and fibrotic lesions.

Objective To report single-center experience on CBA combined with LAAC in treat-ment of AF.Methods A retrospective study was conducted on 27 AF patients undergoing one-stop surgery of CBA combined with LAAC in Department of Cardiovascular Diseases of the People's Hospital of Liaoning Provincie from August 2020 to November 2022.The efficacy and safety of the surgery were analyzed.Results There were 22 patients(81.5％)with LAmbre and 5 patients with Watchman(18.5％,including one case of 24 mm Watchman FLX).All the patients achieved complete pulmonary vein isolation,and conversion to sinus rhythm during operation.During a mean follow-up of 30.0±9.2 months,24 patients(88.9％)maintained sinus rhythm at 12-month follow-up,and 22 patients(81.5％)maintained sinus rhythm at 24-month follow-up.TEE at 3 months after operation displayed that all the devices were in good positions and no PDL or DRT was observed.In the 11 patients undergoing cardiac enhanced CT in 12-36 months after surgery,PDL was detected in one patient(9.1％),and uncomplete endothelialisation of the device was observed in another one(9.1％)using the Watchman device.TEE at 26 months revealed one patient(3.7％)of DRT.Conclusion One-stop surgery of CBA combined with LAAC is a feasible treatment option for patients with NVAF and at high risk of stroke.

Objective:To explore the changes of gait flexibility and stability in patients with Parkinson's disease (PD) 2 years after deep brain stimulation (DBS).Methods:Twenty PD patients accepted DBS in Department of Neurosurgery, Tianjin Huanhu Hospital from October 2019 to November 2021 were enrolled. Motor symptoms were evaluated by Movement Disorder Society-unified Parkinson's disease rating scale III (MDS-UPDRS-III) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognition and 39-item Parkinson's disease questionnaire (PDQ-39) was used to evaluate the quality of life at preoperative medication-on state and postoperative medication-on state. A three-dimensional gait analyzer was used to record the gait parameters during Instrumented Stand and Walk test (ISAW) at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state. Differences in motor symptom scores, cognitive scores, quality of life scores, as well as changes in gait flexibility and stability were compared before and after DBS.Results:(1) The MDS-UPDRS-Ⅲ scores at preoperative medication-off state, postoperative medication-off state, and postoperative medication-on state ([45.30±12.57], [24.95±10.74], [15.80±7.19]) were decreased successively, with significant differences ( P<0.05).(2) Compared with those before surgery, PD patients had significantly lower levodopa equivalent daily dose (LEDD), total scores of PDQ-39, and scores of question 9 "degree of concern about falling" in PDQ-39 at 2 years after DBS ([711.84±343.99] mg/d vs. [549.30±301.08] mg/d, 47.00[30.00, 64.00] vs. 13.50[7.75, 27.00], 2.00[0.00, 3.00] vs. 0.00[0.00, 1.75], P<0.05). (3) Compared with that at preoperative medication-off state, the arm swing velocity at postoperative medication-on state statistically increased in PD patients ( P<0.05); compared with those at preoperative medication-off state, the arm swing range and turning speed at postoperative medication-off and medication-on states significantly increased in PD patients ( P<0.05); compared with that at preoperative medication-off state, the turning duration at postoperative medication-off state statistically decreased in PD patients ( P<0.05). Compared with that at preoperative medication-off state, the range of motion of the trunk in the horizontal plane at postoperative medication-off and medication-on states increased significantly in PD patients ( P<0.05); compared with that at preoperative medication-off state, the range of motion in the sagittal plane of the lumbar, coronal plane of the trunk, and sagittal plane of the trunk all increased significantly in PD patients at postoperative medication-on state ( P<0.05); the mean velocity and root mean square acceleration at postoperative medication-on state increased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05); conversely, the swing frequency at postoperative medication-off state decreased significantly in PD patients compared with that at preoperative medication-off state ( P<0.05). Conclusion:Two years after DBS, PD patients exhibit obviously improved gait, with enhanced flexibility, and dynamic and static stability.

Objective:To investigate the effects of improving the prenatal multidisciplinary consultation mode on the outcomes of fetuses with structural malformations.Methods:Clinical data of pregnant women attending the Prenatal Multidisciplinary Consultation Center, jointly established by the Obstetrics & Gynecology Hospital of Fudan University and the Children's Hospital of Fudan University from January 2004 to December 2019, were retrospectively collected and analyzed. In 2014, the center optimized the multidisciplinary consultation mode to achieve a more individualized approach to genetic testing based on more accurate imaging diagnosis and deeper cooperation between the obstetrics and pediatrics teams. Differences in the number of cases, structure of the diseases, genetic testing results, outcomes, and prognosis between the improved group (enrolled from January 2014 to December 2019) and the baseline group (enrolled from January 2004 to December 2013) were compared. The Chi-square test was used for statistical analysis. Results:(1) This study recruited 5 977 pregnant women, including 3 424 in the baseline group and 2 553 in the improved group. The main indications for consultation were fetal factors [97.2% (5 812/5 977)], among which congenital structural malformations accounted for 77.5% (4 503/5 812). There was a significant difference in the systematic distribution of congenital structural malformations between the two groups ( χ2=141.31, P<0.001). The proportion of malformations involving the central nervous, cardiovascular, and urinary systems ranked in the top three in both groups. (2) The percentage of women receiving genetic testing was higher in the improved group than in the baseline group [26.7% (682/2 553) vs. 15.9% (546/3 424), χ2=103.87, P<0.001] and the positive rate of genetic testing was also higher in the improved group [19.9% (136/682) vs. 9.9% (54/546). χ2=23.42, P<0.001]. (3) Among the 5 977 cases, 418 (7.0%) were lost to follow-up; 1 741 (29.1%) opted for pregnancy termination; 123 (2.2%) had intrauterine fetal death; and 3 695 (61.8%) were live births. The rate of pregnancy termination in the improved group was lower than that of the baseline group [27.7% (707/2 553) vs. 30.2% (1 034/3 424), χ2=4.45, P=0.035]. (4) In the 1 741 cases with pregnancy termination, fatal cardiovascular system malformations ( n=413, 23.7%), central nervous system malformations ( n=377, 21.7%), multiple malformations ( n=258, 14.8%), and chromosomal abnormalities ( n=162, 9.3%) were the main causes. The top five diseases leading to pregnancy termination were cleft lip and palate [59.0% (46/78)], meningocele (5/9), gastroschisis/omphalocele [49.3% (33/67)], diaphragmatic hernia [46.5% (33/71)], and skeletal malformations [40.9% (83/203)]. The rates of pregnancy termination due to gastroschisis/omphalocele, diaphragmatic hernia, and skeletal malformations in the improved group were all lower than those in the baseline group [57.4% (27/47) vs. 30.0% (6/20), χ2=4.23; 59.0% (23/39) vs. 31.3% (10/32), χ2=5.43; 51.8% (72/139) vs. 17.2% (11/64), χ2=21.72; all P<0.05]. (5) Among the 3 695 live births, 1 979 (53.6%) were delivered by cesarean section and 1 716 (46.4%) by vaginal delivery; 3 633 (98.3%) survived and 62 (1.7%) died in the neonatal period. The survival rate of newborns in the improved group was higher than that in the baseline group [98.8% (1 648/1 668) vs. 97.9% (1 985/2 027), χ2=4.23, P=0.040]. Among the 62 dead newborns, 51 (82.3%) had fatal structural or chromosomal abnormalities. (6) In the surviving neonates, 372 (10.2%) showed no abnormalities in a postnatal reexamination, and 468 (12.9%) received surgical treatment in the neonatal period. The other 2 793 cases received no treatment in the neonatal period but were followed up regularly. Conclusion:The optimized prenatal multidisciplinary consultation mode effectively reduces the rate of pregnancy termination due to non-fatal single structural malformations and increases the survival rate of newborns.

Objective To examine the regulation of malignant progression of colorectal cancer by LINC00626 via the JAK1/STAT3/KHSRP signaling axis and its molecular mechanism.Methods 96 individuals diagnosed with colorectal cancer at our hospital during June 11,2021 and June 11,2023 were chosen as research subjects,and their cancerous tissue and nearby normal tissue were collected.Cultivate colorectal cancer cell lines(SW620,HCT116,HT29,DLD-1,LOVO,Caco-2)and normal colorectal cells(NCM460)in vitro,and detect the expression of LINC00626 and KHSRP in colorectal cancer tissue and cell lines using qRT-PCR.Screening out cell lines infected with lentivirus,SW620 and HCT116 cell lines were transfected with knockdown lentivirus and its control,while HT29 and DLD-1 cell lines were transfected with overexpressing lentivirus and its control,respectively.Select stable transfected cell lines for cell function experiments to detect proliferation,migration,and invasion abilities.Detection of the effect of LINC00626 on the growth and migration of colorectal cancer tumors in live mouse experiments.The expression level of KHSRP protein in stable labeled cells was determined using a western blot analysis.Rescue experimental research on the regulatory relationship between LINC00626 and KHSRP.Results qRT-PCR showed low expression of LINC00626 and high expression of KHSRP in colorectal cancer tissues and cell lines.Cell function experiments showed that compared with the sh-NC group,the sh-LINC00626 group promoted cell proliferation,migration,and invasion in SW620 and HCT116 cells,while the overexpression group showed the opposite.Cell rescue experiments showed that,LINC00626+KHSRP significantly reversed the promotion effects of knocking down LINC00626 on cell proliferation,migration,and invasion.In the nude mouse experiment,com-pared with the sh-NC group,the sh-LINC00626 group showed a significant increase in tumor volume and weight,cell proliferation rate,and the number of lung metastases from colorectal cancer in the nude mice;Overexpression results in the opposite.The signal pathway experiment revealed that relative to the sh-NC group,the expression levels of JAK1 and STAT3 mRNA in the sh-LINC00626 group were significantly increased,whereas the results in the overexpression group were the opposite.Conclusion LINC00626 suppression the malignant progression of colorec-tal cancer metastasis through the JAK1/STAT3/KHSRP signaling axis.

Objective·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus(SLE)and other autoimmune diseases based on laboratory indications,and to evaluate its efficacy.Methods·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group,and 535 patients with other autoimmune diseases during the same period were selected as control group.Basic information and laboratory test indicators of the SLE group and control group were collected and compared.The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3,respectively.LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE.The nomogram for differential diagnosis of early SLE(SLE nomogram)was established according to the selected main risk factors.Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram.The receiver operator characteristic curve(ROC curve)and decision curve analysis(DCA)were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram,respectively.The"DynNom"package of R language was used to convert the nomogram into an electronic calculator,and its consistency with SLE nomogram was verified by data from 3 groups of patients.Results·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE,including antinuclear antibody(ANA),anti-double-stranded DNA(anti-dsDNA)antibody,anti-ribonucleoprotein antibody/anti-Simth antibody(anti-nRNP/Sm),anti-ribosomal P protein(anti-P)antibody,anti-nucleosome antibody(ANuA)and urinary protein(PRO),which were used to construct the SLE nomogram.The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set,respectively,and its area under the curve(AUC)was 0.889 and 0.869,respectively.The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95,the model achieved more net benefit.The prediction results of the electronic calculator showed that when ANA(titer 1∶100)was positive in SLE patient No.1,the prevalence was 0.166;when both ANA(titer 1∶100)and ANuA(titer 1∶100)were positive in patient No.2,the prevalence was 0.676;when all of PRO,ANA(titer 1∶100),ANuA(titer 1∶100)and anti-P antibody(titer 1∶100)were positive in patient No.3,the prevalence was 0.990,which was consistent with the differential diagnosis results of the SLE nomogram.Conclusion·The established SLE nomogram based on ANA,anti-dsDNA antibody,anti-nRNP/Sm,anti-P antibody,ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases,and have important clinical application value.

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.

BACKGROUND:Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth,which has a good application prospect in the treatment of bone diseases.However,how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE:To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS:Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate,and the labeling results were detected by fluorescence imaging and UV spectral scanning.Successfully labeled Cornus cervi Colla was injected into mice by gavage,and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy,and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager.The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy.Samples were taken from serum and bone at the time of the strongest fluorescence,and gel electrophoresis was carried out on serum and bone tissue protein solutions,and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION:The fluorescent markers were successfully separated by dextran gel chromatography,and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful,and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%.The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours.The fluorescence images of mice at different times were the same as those of bilateral femur and tibia,indicating that Cornus cervi Colla could play a role by entering the bone.Compared with UniProt database,secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin.It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role.

Objective     To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. Methods    Clinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results     Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P<0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion     In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.

[Objective]People infected with Hepatitis B are often divided into hepatitis B carriers and hepatitis B patients based on whether ALT is normal or not,and ALT ≥ 2UNL is one of the indications for clinical antiviral treatment,but no sufficient evidence to justify this. In order to explore the theoretical basis,the paper investigated the effects of hepatitis B virus(HBV) on hepatic stellate cells(HSCs).[Methods]A total of 132 chronic hepatitis B patients with different viral loads and ALT levels were randomly selected as the study subjects. Of these patients,those with ALT≥2UNL were treated with antiviral therapy and followed up for 24 weeks. The effects of HBV on HSCs before and after the treatment were compared and analyzed. HSCs proliferation was detected by MTT method,HSCs cell cycle by flow cytometry,and expression of TGF-β1,Smad3,Smad7,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins by RT-PCR and Western blotting,respectively.[Results]At the normal ALT level,HBV with different viral loads had no significant effect on the proliferation,cell cycle and cell secretion of the HSCs. At the abnormal ALT level,especially when ALT ≥ 2UNL,with the increase of virus loads,HSCs proliferation accelerated;cells in the G0/G1 phase decreased significantly and cells in the S and G2/M phases increased significantly;the expression of TGF-β1,Smad3,α-SMA,collagen Ⅰ,collgen Ⅲ mRNAs and corresponding proteins increased significantly,but Smad7 mRNA and protein expression decreased significantly,the differences were statistically significant. HBV showed a significantly lower effect on HSCs after the antiviral therapy than before.[Conclusions]This paper reveals the differential effects of HBV on HSCs at different ALT levels and presents a comparative analysis of the effects before and after the antiviral therapy,which provides a theroretical basis for identifying the ALT level as an indication for HBV antiviral therapy.