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

Metabolic dysfunction-associated fatty liver disease （MAFLD） has a relatively high prevalence rate around the world and is closely associated with the development of various extrahepatic malignancies， among which pancreatic cancer exhibits the highest mortality rate. However， the underlying mechanism between MAFLD and pancreatic cancer remains unclear. This article systematically introduces the latest epidemiological evidence of the association between MAFLD and pancreatic cancer， reviews the research advances in pathogenesis， and evaluates the impact of MAFLD severity and high-risk factors （such as nonalcoholic fatty pancreatic disease and intraductal papillary mucinous neoplasm） on the risk of pancreatic cancer. This article points out that insulin resistance， adipokines， and gut dysbiosis may be the key mechanisms of MAFLD promoting the onset of pancreatic cancer， and it also highlights the presence of heterogeneity in current studies. Large-scale prospective cohort studies are needed in the future to further validate the causal relationship and explore more effective strategies for risk stratification.

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 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.

The high intra- and inter-tumor heterogeneity of gastric cancer leads to a great difference in the immunotherapy efficacy and the prognosis among patients. Several biomarkers, including programmed death-ligand 1, human epidermal growth factor receptor 2, the features of tumor microenvironment, the peripheral blood inflammatory markers and Claudin18.2 have predictive value in the immunotherapy efficacy and the prognosis of gastric cancer patients, which might help the clinicians find the potential patients who will benefit from immunotherapy, and achieve the goal of precision medicine.

[Objective]To investigate the association between screen content and the frequency of screen exposure at the age of one and a half years and hyperactive behavior in preschool,and to explore how the association is affected by the interaction between outdoor activities and screen behaviors,which could provide theoretical basis and feasible solutions for the prevention and intervention of behavioral problems in childhoood.[Methods]The survey was conducted from June 2022 to June 2023 in Huicheng District,Huizhou (China) stratified by whole cluster sampling methods. Parents and teachers of 5648 children in 61 kindergartens were sampled for questionnaire surveys. The Conners Teacher Rating Scale (TRS) was used to investigate hyperactive behavior. A self-administered questionnaire was used to investigate basic demographic information of children,screen content,frequency of screen exposure and outdoor activities at the age of one and a half years. Multivariate logistic regression was used to explore the association between video screen behavior and hyperactive behavior and its interaction with outdoor activities by controlling for covariates such as children's age,gender,and parental education.[Results]Result showed the overall prevalence of 3.2％ for hyperactive behavior,2.1％ for conduct problems,2.1％ for hyperactivity problems,1.3％ for inattention-passivity problems,and 0.9％ for hyperactivity index. After adjusting for confounding factors,multiple logistic regression analysis showed that screen exposure of "two to four times a week" at one and a half years old was associated with an increased detection rate of hyperactive behaviors in preschool children,with an estimated ORs (95％ CI) of 1.682 (1.141,2.480). Daily screen exposure was associated with increased detection rates of hyperactive behavior,conduct problems,hyperactivity issues,inattention-passivity problems,and hyperactivity index in pre-school age. The estimated ORs (95％ CI) were 2.136 (1.218,3.746),2.321 (1.185,4.546),2.300 (1.208,4.380),2.776 (1.267,6.085) and 3.640 (1.525,8.687),respectively. But the above associations were not found in children who were engaged in daily outdoor activities at the age of one and a half years (P value for interaction<0.001). No association was found between screen content and hyperactive behavior (P>0.05).[Conclusions]Frequency of screen exposure in early childhood is significantly associated with hyperactive behavior problems in preschool,and outdoor activities could weaken the correlation between high-frequency screen exposure and hyperactive behavior,suggesting that parents and schools should prioritize scientifically guiding children's video viewing behavior and outdoor activities,ensuring a well-arranged daily life,to lay a good foundation for the healthy development of children's behavior.

Objective:To explore the efficacy and safety of low-and medium-intensity resistance exercise in patients with chronic heart failure(CHF)combined with sarcopenia.Methods:In the randomized controlled study, 100 elderly patients with CHF combined with sarcopenia who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Baotou Medical College from October 2020 to August 2022 were selected and divided into the control group and the intervention group according to the randomized numerical scale method.In the control group, angiotensin-converting enzyme inhibitors/angiotensin receptor inhibitors, β receptor antagonists, diuretics and other standard heart failure medications were routinely given, as well as nutritional support, health education and guidance; in the intervention group, low-intensity resistance exercise was given in addition to the treatment of the control group, and the two groups were evaluated for the NYHA cardiac function classification, grip strength, 5 times sitting time, 6-meter walking time, serum B-type natriuretic peptide level before and after 12 weeks of treatment; limb skeletal muscle mass index(ASMI), visceral fat area, extracellular water ratio were measured by body composition analyzer; right ventricular internal diameter, left atrial internal diameter, left ventricular end-diastolic internal diameter, left ventricular ejection fraction(LVEF) were measured by echocardiography.Changes in each index before and after treatment were compared between the 2 groups.Serious adverse cardiovascular events related to training were followed up by outpatient clinic visits or telephone at 4-week interval over 12 weeks.Results:30 cases were dislodged because they could not adhere to the exercise or could not follow up on time, and finally 70 patients were included, 27 in the control group and 43 in the intervention group.Compared with pre-treatment, grip strength[(17.73±4.54)kg vs.(17.00±4.32)kg, t=8.969], limb skeletal muscle mass[(17.57±3.41)kg vs.(17.24±3.34)kg, t=7.170], and ASMI[(6.02±0.72)kg/m 2vs.(5.85±0.67)kg/m 2, t=6.866]were elevated in the intervention group after 12 weeks(all P<0.05); 5 times sitting up time[(16.17±3.25)s vs.(14.54±3.21)s, t=12.808, ]and 6-meter walking time[(12.30±3.24)s vs.(10.76±3.14)s, t=9.391]shortened(all P<0.05).Compared with pre-treatment, the intervention group showed reduced left ventricular end-diastolic internal diameter[(59.62±9.07)mm vs.(58.48±9.71)mm, t=4.552], increased LVEF[(34.69±7.93)% vs.(35.88±7.92)%, t=4.752], and increased extracellular water ratio[(39.27±7.74)% vs.(38.92±7.41)%, t=6.058]after 12 weeks(all P<0.05).At 12 weeks of follow-up, no training-related serious adverse events occurred in the intervention group.The difference in the incidence of serious adverse cardiovascular events between the two groups(3.70% vs.2.33%, P>0.05)was not statistically significant. Conclusions:Treatment combined with low-and moderate-intensity resistance exercise improves muscle mass, muscle strength, physical function, and cardiac function in elderly patients with CHF combined with sarcopenia without increasing the incidence of adverse events.

Objective To investigate the potential of immune-inflammatory markers and the characteristics of magnetically controlled capsule endoscopy in distinguishing gastric adenocarcinoma from precancerous lesions,as well as to develop and validate a risk prediction model.Methods Retrospective analysis was conducted on medical records of 578 patients who underwent magnetic controlled capsule endoscopy at our hospital between January 2021 and December 2023.Following the principle of Pareto's law(80/20 rule),they were randomly divided into a training set(462 cases)and a validation set(116 cases).Magnetic controlled capsule endoscopy and blood cell tests were performed,with pathological diagnosis results serving as the"gold standard",to classify patients into groups of gastric adenocarcinoma and precancerous lesions.The magnetic controlled capsule endoscopic features,neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR)in patients with gastric adenocarcinoma and precancerous lesions were compared to develop and validate a risk diagnostic model for gastric adenocarcinoma.Results Among the 462 patients who underwent magnetic controlled capsule endoscopy,gastric adenocarcinoma was diagnosed in 76 cases through pathological examination,accounting for 16.45%(76/462),while precancerous lesions were observed in 386 cases,accounting for 83.55%(386/462).In the validation set of 116 patients who underwent gastric endoscopy,there were 22 cases of gastric adenocarcinoma,representing an incidence rate of 18.97%(22/116),and a total of 94 cases with precancerous lesions,accounting for an incidence rate of 81.03%(94/116).No statistically significant differences(P＞0.05)were found between the two groups regarding lesion size,border appearance,mucus presence or lesion morphology.However,compared to the precancerous lesion group,the proportion of whitish coloration as well as irregular surface microstructure and grid-like microvessels was significantly higher in the gastric adenocarcinoma group(P＜0.05).Moreover,both NLR and PLR values were significantly higher in the gastric adenocarcinoma group compared to those in the precancerous lesion group(P＜0.05).Irregular surface microstructure(OR=2.213,95%CI:1.288～3.801),irregular grid-like microvessels(OR=2.489,95%CI:1.458～4.249),NLR(OR=2.369,95%CI:1.389～4.046),and PLR(OR=3.016,95%CI:1.767～5.148)were identified as risk factors for gastric adenocarcinoma(P＜0.05).The sensitivity of the risk model for diagnosing gastric adenocarci-noma in the training set was 0.800(95%CI:0.716～0.891),with a specificity of 0.783(95%CI:0.694～0.851)and an area under the curve of 0.858(95%CI:0.787～0.931).In the validation set,the sensitivity for diagnosing gastric adenocarcinoma was 0.861(95%CI:0.771～0.945),with a specificity of 0.769(95%CI:0.683～0.841)and an area under the curve of 0.844(95%CI:0.765～0.923).Conclusion The surface microstructure,microvas-cular morphology,NLR,and PLR of gastric lesions are correlated with the occurrence of gastric adenocarcinoma.Developing a risk diagnostic model facilitates early identification and diagnosis of gastric adenocarcinoma.