Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.

Patent foramen ovale(PFO)is a congenital heart disease with a relatively high prevalence in the population.Past studies have clarified its association with strokes and recognized the significance of PFO closure for PFO-related strokes.In recent years,research on diseases related to PFO has gradually increased and deepened our understanding.Meanwhile,the number of closure treatments for PFO in China has also significantly increased.This article reviews the latest research progress in the PFO field for the year 2023,mainly including the expansion of the spectrum of PFO-related diseases(such as epilepsy,unexplained syncope,etc.),exploration of the mechanisms of disease,and means of risk assessment.Regarding PFO closure treatment,this article introduces the latest research results concerning the effects of closure and prognosis,as well as the relationship between closure treatment and atrial fibrillation.China has always been in a leading position in the development of new devices for PFO closure,and this article also introduces the latest achievements in this area.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

"Shaoyang as the pivot"is one of the important concepts in the theory of traditional Chinese medicine.It is believed that shaoyang is located between half exterior and half interior,which reaches the muscular striae and the exterior and connects with the internal organs,and plays the role of promoting qi movement,regulating water channel and distributing ministerial fire.The dysfunction of shaoyang pivot leads to the disorder of qi movement,abnormal water metabolism,and stagnation or hyperactivity of ministerial fire.Cholinergic urticaria is a special type of urticaria caused by the disorder of cholinergic nerve conduction,which has a long course of disease and is difficult to be cured.According to the clinical characteristics of the disease,Professor SUI Dao-Shun believes that the dysfunction of shaoyang pivot is the core pathogenesis of cholinergic urticaria.Emotional disorders lead to the dysfunction of pivot,and then cause the disordered flow of qi and fluid and internal disturbance of hyperactive ministerial fire,which induce the disharmony between nutritive qi and defensive qi,and the failure of being against the pathogens.Finally,wind pathogen attacks the skin and muscular striae and becomes latent,and results in cholinergic urticaria.For the treatment of cholinergic urticaria,Chaihu Guizhi Decoction can be used as the basic prescription to harmonize shaoyang,expel pathogens and release exterior.Corresponding modification of herbal medicines should be performed for various syndromes caused by the dysfunction of shaoyang pivot such as qi stagnation,dampness retention and heat stagnation during the clinical application.The prevention and treatment of cholinergic urticaria based on the theory of shaoyang as the pivot can provide thoughts for the clinical treatment of cholinergic urticaria.

Objective To compare the efficacy and safety between hypofractionated radiotherapy(HyRt)and conventional radiotherapy after breast-conserving surgery.Methods This study was a single-center,prospective,randomized controlled study.Eighty-three patients with pTis-T2N0M0 breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included.The patients received breast-conserving surgery+sentinel lymph node biopsy(SLNB).After surgery,they were treated with intensity modulated radiation therapy(IMRT).According to random table method,patients were divided into HyRt group(n=41)and conventional radiotherapy group(n=42).The dose of organs at risk,treatment efficacy,treatment failure modes,and radiotherapy related adverse reactions were analyzed in the two groups.The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0,including radiation dermatitis,radiation pneumonia,breast/skin fibrosis,pulmonary fibrosis,etc.Results Eighty-three patients with breast cancer were included,with a median age of 44(26-67)years.There was no statistically significant difference in clinical parameters such as age(P=0.443),TNM stage(P=0.335),molecular typing(P=0.333),degree of differentiation(P=0.617),and pathological type(P=0.127)between the two groups of patients.Compared with conventional radiotherapy group,the V5(25.6％vs.33.8％,P=0.015),V20(13.3％vs.17.2％,P=0.042),and the mean radiation dose(MLD;7.4 Gy vs.10.4 Gy,P=0.020)of the affected lung of HyRt group significantly decreased.Only 3 patients in this study experienced distant metastasis,and no regional lymph node metastasis or local recurrence was observed.There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group(94.4％vs.85.2％,P=0.818).Compared with conventional radiotherapy group,the incidence of≥grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced(2.4％vs.21.4％,P=0.015).There was no difference in the incidence of grade Ⅰ breast/skin fibrosis(19.5％vs.14.3％,P=0.570)between the two groups,and no grade Ⅲ radiotherapy-related side effects were observed in the two groups.Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy,the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions.HyRt can be used as the first option of radiation therapy.

Objective:To investigate the changes of left ventricular systolic function in patients after pacing in differ-ent sites of right ventricle.Methods:The clinical data of 95 patients requiring right ventricular pacing who were ad-mitted to our hospital from February 2018 to May 2020 were collected.According to pacing site,they were divided into right ventricular apex pacing(RVAP)group(n=47)and right ventricular outflow tract septal pacing(RVSP)group(n=48).The pacing threshold,perception threshold,electrode impedance,left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),stroke volume(SV),left ventricular ejection fraction(LVEF)were compared between the two groups.According to incidence of cardiac insufficiency on one year after pacing,patients were divided into cardiac insufficiency group(n=18)and normal cardiac function group(n=77).Influencing factors of cardiac insufficiency in patients requiring right ventricular pacing were analyzed.Results:Compared with one week after pacing,on one year after pacing,perception threshold[(11.51±1.21)mV vs.(12.11±0.81)mV]significantly increased in RVAP group,P=0.004.Compared with RVAP group on one year after pacing,there were significant rise in LVESV[(25.32±7.63)ml vs.(29.77±12.36)ml],LVEDV[(58.30±15.71)ml vs.(68.33±25.31)ml],SV[(31.36±10.73)ml vs.(41.29±16.15)ml],and significant reductions in LVEF[(60.55±8.76)％vs.(54.10±6.44)％]and proportion of cardiac insufficiency(27.66％vs.10.42％)in RVSP group,P＜0.05 or＜0.01.Non-conditional multivariate Logistic regression model analysis indicated that LVEF was inde-pendent protective factor for cardiac insufficiency in patients requiring right ventricular pacing(OR=0.854,P=0.003),while RVAP and age ≥60 years were its independent risk factors(OR=9.041,4.145,P=0.003,0.024).Conclusion:Compared with right ventricular apex pacing,right ventricular outflow tract septal pacing can significantly improve stroke volume,and incidence rate of cardiac insufficiency significantly reduces.

Objective:To construct a prognostic nomogram based on epithelial-stromal interaction protein 1(EPSTI1)and predict the pro-gnosis of clear cell renal cell carcinoma(ccRCC).Methods:A retrospective analysis was performed from January 2012 to December 2015 at The First Affiliated Hospital of Fujian Medical University,on 221 patients with ccRCC who underwent surgical treatment in our center and 533 patients with ccRCC in The Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)staining was performed on adjacent nor-mal and cancerous tissues to analyze the expression level of EPSTI1 and its correlation with clinicopathological characteristics.Kaplan-Meier survival analysis was performed for the overall survival(OS)and disease-free survival(DFS)of patients with high and low EPSTI1 expression levels.Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors for OS,and a nomogram model was constructed and verified.Results:The IHC scores and mRNA expression levels of EPSTI1 were significantly higher in ccRCC tissues than in normal tissues(all P<0.001).EPSTI1 was expressed at higher levels in cancer tissues at higher T stages(P=0.036,P=0.006).The EPSTI1 protein expression level was related to the maximum tumor diameter and TNM stage(P=0.002,P=0.032,respectively).The OS and DFS were higher in the low-EPSTI1-expression group than the high-EPSTI1-expression group(P=0.046,P=0.003,P=0.001).Univariate and multivariate Cox regression analyses showed that a high EPSTI1 protein expression level,WHO/ISUP grade,and AJCC/TNM stage were independent risk factors for poor prognosis(P=0.009,P=0.039,P<0.001).The prognostic nomogram model constructed based on the above variables was su-perior to the AJCC/TNM stage in predicting the 5-year OS,and the calibration curve showed that the predicted value of the model was con-sistent with the actual value.Conclusions:The nomographic model based on EPSTI1,AJCC/TNM staging and WHO/ISUP staging has a strong predictive ability for the prognosis of renal clear cell carcinoma.

Objective To investigate the nutritional status of children with cystic fibrosis(CF)and understand the correlation between malnutrition and clinical characteristics as well as lung function.Methods A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023.Clinical characteristics of CF children with different nutritional statuses were compared,and the correlation between malnutrition and lung function was analyzed.Results A total of 52 CF children were included,comprising 25 boys(48％)and 27 girls(52％),aged between 7 months and 17 years.Respiratory symptoms were the predominant clinical manifestations(96％,50/52).The prevalence of malnutrition was 65％(34/52),with moderate/severe malnutrition being the most common(65％,22/34).The malnutrition group had a longer duration of illness,higher proportion of digestive system symptoms,and lower levels of serum albumin(P＜0.05).Pulmonary function parameters,including forced expiratory volume in one second as a percentage of the predicted value,ratio of forced expiratory volume in one second to forced vital capacity,forced expiratory flow at 25％of forced vital capacity exhaled,forced expiratory flow at 50％of forced vital capacity exhaled,forced expiratory flow at 75％of forced vital capacity exhaled,and maximum mid-expiratory flow as a percentage of the predicted value,were lower in the malnutrition group compared to the normal nutrition group(P＜0.05).Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters(P＜0.05).Conclusions The prevalence of malnutrition is high in CF children and is associated with decreased lung function.CF children with higher body mass index have better lung function.Therefore,screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.[Chinese Journal of Contemporary Pediatrics,2024,26(3):275-281]