OBJECTIVES: To study the effect of CDC20 knockdown on proliferation, migration and invasion of cervical cancer cells and its underlying mechanism. METHODS: CDC20 expression in cervical cancer tissues was analyzed using the TCGA database, and the protein expressions of CDC20 and β-Catenin in clinical specimens of cervical cancer and adjacent tissues were detected using immunohistochemistry. A dual target sgRNA2&7 sequence for CDC20 gene was designed for CDC20 gene knockdown in cervical cancer C33A cells using CRISPR/Cas9 technology, and CDC20 mRNA and protein expression levels in the transfected cells were detected using qRT-PCR and Western blotting. The changes in proliferation, cell cycle, apoptosis, migration and invasiveness of the transfected cells were evaluated using colony-forming assay, fluorescence activated cell sorting (FACS) and Transwell assay. In the animal experiment, naïve C33A cells and the cells with CDC20 knockdown were injected subcutaneously into the left and right axillae of nude mice (n=5) to observe tumor growth. The expressions of CDC20 and β-Catenin proteins in transfected cells and the xenograft were analyzed using Western blotting, and their interaction was confirmed by co-immunoprecipitation (CoIP) and immunofluorescence co-localization assays. RESULTS: Cervical cancer tissues expressed significantly higher CDC20 and β‑Catenin levels than the adjacent tissues. C33A cells with CDC20 knockdown showed reduced proliferation, increased apoptosis, and lowered migration and invasion abilities. CDC20 knockdown significantly suppressed the growth of C33A cell xenograft in nude mice, and the tumor-bearing mice did not exhibit obvious body mass changes. CDC20 and β-Catenin levels were both significantly lowered in C33A cells with CDC20 knockdown. Co-immunoprecipitation and co-localization assays confirmed the interaction between CDC20 and β‑Catenin. CONCLUSIONS CDC20 is highly expressed in cervical cancer tissues, and CDC20 knockdown can suppress proliferation, invasion, and metastasis while enhancing apoptosis of C33A cells, which is closely related with the regulation of the Wnt/β-Catenin signaling pathway.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; Cdc20 Proteins/genetics* ; Cell Proliferation ; Animals ; Cell Movement ; Neoplasm Invasiveness ; Apoptosis ; Mice, Nude ; beta Catenin/metabolism* ; CRISPR-Cas Systems ; Mice ; Cell Line, Tumor ; Gene Knockout Techniques ; Neoplasm Metastasis

Objective:To treat the Crohn's disease(CD)patients with ustekinumab(UST),to eva-luate their clinical and endoscopic remission,and to evaluate their transmural response(TR)and trans-mural healing(TH)condition using intestinal ultrasonography(IUS).Methods:Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to Au-gust 2022,who were treated with UST for remission induction and maintenance therapy.All the patients were evaluated on both week 8 and week 16/20 after treatment,including clinical,biochemical indica-tors,colonoscopy and IUS examination.Results:A total of 13 patients were enrolled in this study,inclu-ding 11 males and 2 females.The minimum age was 23 years,the maximum age was 73 years and the mean age was 36.92 years.All the patients were in the active stage of disease before treatment,and the average Best Crohn's disease activity index(Best CDAI)score was 270.12±105.55.In week 8,the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66(t=4.977,P＜0.001).Eight patients achieved clinical remission while 5 patients remained in the active stage.Nine patients underwent colonoscopy evaluation.The average simple endoscopic score for Crohn's disease(SES-CD)score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483,P=0.048)in week 16/20.Four patients achieved endoscopic remission while 5 patients did not.In week 8,5 pa-tients achieved TR,2 patients achieved TH,the other 6 patients did not get TR or TH.In week 16/20,6 patients achieved TR,3 patients achieved TH while the other 4 patients did not get TR or TH.There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions(Fisher test,P＞0.999).The rate of UST transmural response in the patients who had had previous bio-logical agent therapy was lower than those with no previous biological agent therapy,but there was no sig-nificant statistical difference(Fisher test,P=0.491).Conclusion:After treatment of UST,the clinical and endoscopic conditions of the CD patients had been improved,and some patients could achieve clini-cal remission and endoscopic remission.UST had good TR and TH effects on CD.TR might appear in week 8,and the TR effect increased in week 16/20.There was no significant statistical difference in the TR effect between small intestine and colon lesions.TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents,but the result had no significant statistical difference.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective: To investigate the relationship between urinary monohydroxylated metabolites of hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) and lung function, as well as the role of oxidative stress in these associations, so as to provide a scientific basis for air pollution control and policy formulation. Methods: A panel study was carried out among 45 young healthy adults. Four follow up surveys and health examinations were conducted from November 2017 to October 2018 to measure lung function parameters [forced vital capacity (FVC), second forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and forced expiratory flow between 25% and 75% vital capacity (FEF 25%~75% )], markers of exposure to 7OHPAHs [∑ 7OH PAHs], and markers of oxidative stress[8 hydroxy 2 deoxyguanosine (8 OHdG) and 8 isoprostaglandin F 2α (8 iso PGF 2α )]. The relationship between urinary PAH metabolites and lung function was quantified by linear mixed effects models. Mediation analysis was performed to assess the role of oxidative stress in the relationship between OH PAHs and lung function. Results: The median values of FVC, FEV1, FEVI/FVC, PEF, and FEF 25%-75% were 4.37 L, 3.58 L, 83.00%, 4.38 L/s, and 3.32 L/s, respectively. The results showed that each 1 unit increase in log transformed value of 2 Hydroxyfluorene (2 OHFlu) was associated with a 5.05% decrease ( β %=-5.05%，95% CI =-8.85%--1.09%) in FVC, 4.15% decrease ( β %=-4.15%，95% CI =-7.94%- -0.22% ) in FEV1 and 5.87% decrease ( β %=-5.87%，95% CI =-11.35%--0.05%) in FEF 25%-75% , respectively. Each 1 unit increase in log transformed values of 2 OHFlu and 9 Phenanthrol (9 OHPhe) was associated with a 7.03% decrease ( β %=-7.03%，95% CI =-12.60%--1.11%) and a 7.08% decrease ( β%=-7.08%，95% CI =-13.50%--0.17%) in PEF, respectively. Additionally, urinary ∑ 7OH PAHs had a positive correlation with the levels of urinary 8 OHdG and 8 iso PGF 2α ( r =0.64, 0.69, P <0.01). Meanwhile, the levels of 8 OHdG mediated 17.06% and 15.71% of the association between 2 OHFlu with FVC and FEV1. Conclusion The finding reveales a negative relationship between urinary OH PAHs and lung function among young healthy adults. The 8 OHdG plays a mediated role in the correlation of 2 OHFlu with FVC and FEV1. Active relevant policies are needed to control air pollution and maintain the healthy living conditions of young people.

Objective:To investigate the efficacy of oblique lumbar interbody fusion (OLIF) combined with percutaneous transforaminal endoscopic decompression (PTED) and posterior pedicle fixation through Wiltse approach in the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis.Methods:From June 2017 to February 2022, 103 patients (50 males and 53 females) of lumbar spondylolisthesis accompanied with lumbar spinal stenosis were performed with OLIF combined with PTED and posterior pedicle fixation. The mean age was 64.1±5.2 years (range, 42-87 years). All involved cases were single-segment and included 83 cases of L 4, 5, 17 cases of L 3, 4, and 3 cases of L 2, 3. Among them, 94 cases were performed for the first time, and other 9 were revision surgery treated by posterior lumbar laminectomy previously. The visual analog scale (VAS) was used to evaluate the low back pain and leg pain, and the Oswestry disability index (ODI) was used to evaluate the lumbar function. The VAS and ODI scores were recorded respectively before the operation, at discharge, 1, 3, 6 months after the operation and at the last follow-up. Macnab criteria was used to evaluate the clinical efficacy at the last follow-up. At the same time, imaging measurements were conducted, including the anterior and posterior disc height, segmental lordotic angle, percentage of slip on lateral X-ray film and the vertebral canal area on axial MRI before and after surgery. Results:All of 103 patients were successfully operated in one stage with an average operation time of 177.7±21.5 min (range, 155-220 min), and an average intraoperative blood loss of 55.9±18.3 ml (range, 30-150 ml). The mean follow-up time were 15.1±2.6 months (range, 6-36 months). There were significant differences in both VAS scores of back and leg and ODI scores at each postoperative time point when compared with preoperative ( F=508.25, F=1524.82, F=1148.68, P<0.001). Macnab criteria of the last follow-up was evaluated as follow: excellent in 85 cases, good in 14, fair in 4, and the excellent and good rate was 96.1%. The radiographic results showed the mean immediate postoperative anterior disc height, posterior disc height, segmental lordotic angle, percentage of slip and axial area of the vertebral canal were 15.23±2.97 mm, 9.32±2.31 mm, 14.36°±4.18°, 3.89%±3.11%, 113.37±47.27 mm 2, and thus all of those increased significantly compared to the mean preoperative 11.93±3.17 mm, 7.21±2.03 mm, 6.15°±3.99°, 23.66%±7.79%, 57.63±28.91 mm 2, respectively ( t=7.84, t=7.07, t=14.91, t=27.62, t=9.68, P<0.001). All cases achieved bony fusion during 6-12 months after operation. The incidence of surgery-related complications was 10.7% (11/103). There were 3 cases of end plate fracture and 2 cases of dural injury, which had no complaint after operation. There was 1 case of pedicle screw entering into the spinal canal by mistake, and the symptoms of nerve damage appeared after operation. After 1 year it basically returned to normal. There were 2 cases of thigh numbness and 1 case of psoas major weakness after operation, all of which relieved after 4 weeks. There was 1 case continuous pain of abdominal incision after surgery. There was 1 case of cage subsidence at the last follow-up. Conclusion:OLIF combined with PTED and posterior pedicle fixation through Wiltse approach is a minimally invasive surgical method for the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis. With the combined minimally invasive techniques, the decompression, fusion and fixation of the lumbar spine can be fulfilled perfectly. It has the advantages of minimally invasive, good clical outcome, few complications and rapid rehabilitation.

Objective To investigate the antithrombotic therapy for acute myocardial infarction patients after PCI stenting combined with tricuspid valve repair. Methods The risk of bleeding and embolization was evaluated, relevant data were reviewed, professional knowledges of pharmacy were utilized through the whole treatment process, individualized medication plan for patients was designed and used. Results A better therapeutic effect was achieved through the implementation of pharmaceutical care and medication education to the patients. Conclusion Clinical pharmacists carry out pharmaceutical care in antithrombotic drugs utilities，which could improve the safety level of drug use and provide basis for clinical rational drug use.

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.

ObjectiveTo describe the incidence and distribution characteristics of congenital heart disease in newborns， and to analyze the trend of the notification rate from 2009 to 2018 in Chongming District， Shanghai. MethodsBased on the shanghai birth defects surveillance system， newborns delivered in all medical institutions in Chongming District from 2009 to 2018 were examined for congenital heart disease at birth and followed up to 42 days. The notification rate and trends of various congenital heart diseases were described. ResultsThere were 548 cases of neonatal congenital heart disease in Chongming District from 2009 to 2018， and the notification rate was 20.11‰ （95%CI： 18.47‰-21.85‰）， with statistically significant differences between years during the study period （Z=10.616， P<0.001）. The four most common types of congenital heart disease were patent ductus arteriosus （313， 11.49%）， patent foramen ovale （312， 11.45%）， atrial septal defect （88， 3.64%） and ventricular septal defect （73， 2.68%）. Majority of the congenital heart disease cases were patent ductus arteriosus and patent foramen ovale that could be further closed during growth and development. Isolated patent ductus arteriosus and isolated patent foramen ovale accounted for 18.61% and 23.18% respectively of the total cases. ConclusionThe notification rate of congenital heart disease in Chongming District shows a trend of fluctuating decline followed by an increase. Community follow-up and outcome tracking should be strengthened for children with congenital heart disease， especially those with patent ductus arteriosus or patent foramen ovale.

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.