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

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To observe the clinical efficacy of Huangqi Danggui Compound Decoction(mainly composed of Astragali Radix,Angelicae Sinensis Radix,etc.)combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due of qi and blood depletion type.Methods A total of 138 patients diagnosed with postpartum low back pain from March 2021 to February 2024 in the outpatient and inpatient departments of the Second Affiliated Hospital of Hebei University of Chinese Medicine were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 69 cases in each group.The control group was treated with Ibuprofen Sustained-Release Capsules combined with Shi's Acupuncture Therapy,while the observation group was additionally treated with Astragalus and Angelica Compound Decoction on the basis of the control group's treatment.Both groups were treated for 4 weeks.After treatment,the clinical efficacy of the two groups was evaluated.The changes in Oswestry Disability Index(ODI)and Visual Analogue Scale(VAS)scores before and after treatment,as well as the SF-36 Quality of Life Scale scores,were observed.The changes in follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2)levels were compared before and after treatment,and the safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 92.75%(64/69),while it was 79.71%(55/69)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the ODI and VAS scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in ODI and VAS scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the SF-36 Quality of Life Scale scores of both groups improved significantly(P＜0.05),and the observation group showed significantly better improvement in SF-36 scores compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the FSH,LH,and E2 levels in the observation group were significantly improved(P＜0.05),and the observation group showed significantly better improvement in FSH,LH,and E2 levels compared to the control group,with a statistically significant difference(P＜0.05).In the control group,the FSH,LH,and E2 levels improved slightly,but there was no statistically significant difference compared to before treatment(P＞0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Huangqi Danggui Compound Decoction combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due to qi and blood depletion can significantly alleviate pain symptoms,improve lumbar function,regulate sex hormone levels,and enhance the quality of life of patients,with significant efficacy and good safety.

Objective To compare the long-term efficacy of intradiscal injection of autologous platelet-rich plasma(PRP)and intradiscal injection of autologous PRP combined with pulsed radiofrequency(PRF)therapy for discogenic back pain(DBP).Methods Prospective inclusion of 98 DBP patients who received treatment at Hai'an People's Hospital from July 2019 to December 2023 was conducted.The patients were randomly divided into study group(receiving PRP combined with PRF,n=50)and control group(receiving PRP only,n=48).The preoperative and the postoperative 1-,3-,6-,and 12-month baseline data,visual analog scale(VAS)score,Roland-Morris Disability Questionnaire(RMDQ)score,Leeds Neurological Symptoms and Signs Score(LANSS),European Society for Quality of Life Five Dimensional Questionnaire(EQ-5D)score,and the use of non-steroidal anti-inflammatory and analgesic drugs were compared between the two groups.Results There was no statistically significant differences in the baseline data and the incidence of intraoperative and postoperative adverse reactions between the two groups(both P＞0.05).At 12 months after surgery,the VAS,RMDQ,LANSS,EQ-5D scores,and the use of non-steroidal anti-inflammatory and analgesic drugs in all patients were significantly better than those before surgery(all P＜0.05).The postoperative 3-,6-,and 12-month VAS,RMDQ,LANSS,EQ-5D scores,and the analgesic dosage in the study group were significantly better than those in the control group(all P＜0.05),and the percentages of patients with pain relief greater than 50％and greater than 80％were also significantly higher than those in the control group(all P＜0.01).Conclusion for the treatment of DBP,both CT-guided intradiscal injection of autologous PRP and CT-guided intradiscal injection of autologous PRP combined with PRF can significantly improve pain,body function,and quality of life in DBP patients,and significantly reduce the use of non-steroidal anti-inflammatory and analgesic drugs.The efficacy of autologous PRP combined with PRF is remarkably better than that of autologous PRP alone.

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 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.

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.