Chronic lymphocytic leukemia(CLL)is one of small B-cell lymphomas and leukemias,characterized as a clonal disease of mature B cells.The disease is remarkably heterogeneous,with the majority of patients having an indolent course,yet they are currently incurable.Abnormal signaling pathways are indispensable in the pathogenesis of CLL.In CLL,the common abnormalities of signaling pathways include B-cell receptor(BCR)signaling,apoptosis,nuclear factor kappa B(NF-κB)signaling and Notch signaling.According to the target in signaling pathways,a series of targeted drugs,such as Bruton's tyrosine kinase(BTK)inhibitors(ibrutinib,zanubrutinib),phosphorylate phosphoinositide 3-kinase(PI3K)inhibitor(duvelisib)and B-cell leukemia/lymphoma 2(BCL2)inhibitor(venetoclax),which have significantly changed the prognosis of patients in clinic.Other targeted drugs,such as fenebrutinib,nemtabrutinib and umbralisib,as well as chimeric antigen receptor T-cell(CAR-T)therapy developed in the field of immuno-oncology and T cell engineering,are currently under trial,with more personalized treatment modalities being explored,which may become potential drug targets in the future.In this paper,relevant literature of CLL was reviewed,and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

Invasive fungal infections play an important factor threatening human health.In recent years, the number of the susceptible population of invasive fungal infections has increased rapidly, leading to a significant increase in the disease burden of human fungi.In 2022, the World Health Organization released a list of key fungal pathogens, aiming to promote global research and investment in fungal infection and antifungal resistance.At present, antifungal drugs are preferred for anti-fungal infection treatment, although the efficacy is limited by the adverse events and drug resistance.Improving the damaged host immune response is a reasonable way to improve the effectiveness of antifungal drugs.This article briefly described the epidemiology of fungal infections, summarized how hosts mediate the clearance of fungi by initiating innate and adaptive immune responses, and discussed the prospects and clinical evidence supporting immunomodulatory therapy for invasive fungal infections.

Objective:To establish the animal model of cervicofacial venous malformations(VMs)by surgical reconstruction of exter-nal jugular vein in sheep.Methods:The external jugular veins of 5 sheep were dissected,and the position,course,branch and exter-nal diameter were observed and measured.The models of VMs with draining and returning veins were constructed by suturing or constric-ting the proximal part of main trunk and ligating or constricting the distal part of the jugular or branch veins.The animal model was eval-uated by Doppler ultrasound,gross observation and histological observation at the 4th week after surgery.Results:The external jugular veins of sheep is in the lateral side of bilateral neck,and the main trunk is formed by the maxillary vein and lingual facial vein.The ex-ternal diameter ranges from 6 to 12 mm,with an average external diameter of 9.3 mm.Immediately after the external jugular vein was sutured and narrowed at the proximal part of the main vein,the distal part of the vein branch was ligated or narrowed,the blood flow speed slowed down and the veins in the model area bulged.4 weeks after surgery,gross observation showed that most veins narrowed and thrombosis was formed in part of the venous lumen.The central region of some specimens was dilated,and the peripheral collateral veins were dilated in some models.Doppler ultrasonography showed that the lumens of most veins were dilated and the returning veins and the inflow veins were narrowed.Colored blood flow was seen in the lumen.Histological observation showed that the structure of vein endothelium and wall was close to the normal vein,and the vein vessel wall of some specimens was thickened.Conclusion:The VMs model estab-lished by external jugular vein of sheep basically meets the re-quirements and is expected to be used in the therapeutic meth-odology research of cervicofacial VMs.

During the occurrence and development of various heart diseases,continuous deterioration of myocardial fibrosis leads to remodeling and dysfunction of the cardiac structure.As a newly discovered mechanically sensitive ion channel,Piezo1 has opened up a new field of research on cellular mechanical transduction.Piezo1 combines a fine force transducer with Ca2+ influx and participates in the regulation of cellular mechanical transduction,thereby regulating cellular biological functions.Recent studies have shown that the biomechanical changes induced by myocardial injury regulate the expression of Piezo1 in cardiomyocytes and cause an imbalance in calcium homeostasis,which plays an important role in the positive feedback loop of myocardial fibrosis.This review summarizes the theoretical basis and related studies of Piezo1 in regulating cardiac fibrosis and suggests that the Piezo1 channel may become a new target for the treatment of cardiac fibrosis,thereby providing a new research horizon for the prevention and treatment of cardiac fibrosis.

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

The clinical demand for occlusal reconstruction increases rapidly with increasing number of patients who have lost their normal occlusion because of tooth wear and dentition defects.Occlusal reconstruction is a special type of restoration defined as a comprehensive restoration of the function of the stomatognathic system by reestablishing a uni-form and stable occlusal relationship between the upper and lower dentitions.Occlusal function analysis is an important part of occlusal reconstruction to achieve accurate restora-tion design and adjustment.Digital occlusal function analysis was conducted to monitor the movement of the mandible and obtain related data for the parameter design of occlusal reconstruction.Preoperative design,intraoper-ative adjustment,and postoperative verification were achieved,thereby improving the efficiency and accuracy of occlusal reconstruction.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To explore the application effect of breakthrough series (BTS) quality improvement model in the prevention of catheter-related bloodstream infection in hospitalized patients with indwelling non-cuffed catheter (NCC).Methods:Using a non synchronous pre and post control study method, convenience sampling was used to select NCC patients from four hospitals in Tianjin from January to September 2022 who received conventional nursing plans as the control group, and NCC patients from February to October 2023 who received nursing plans based on the BTS quality improvement model as the observation group. Compared the incidence of NCC related bloodstream infections between two groups of patients, the implementation of key preventive measures for NCC related bloodstream infections by nursing staff, and patient satisfaction.Results:Among the 984 patients included in the control group, there were 687 males and 297 females, aged (62.43 ± 13.77) years old; among the 959 patients included in the observation group, there were 651 males and 308 females, aged (61.96 ± 13.89) years old. After applying the improved model, the incidence of NCC related bloodstream infections in the observation group was 0.12‰ (1/8 676), lower than the control group′s 0.71‰ (7/9 827), and the difference was statistically significant ( χ 2=4.37, P<0.05) ;the implementation rate of key measures for preventing NCC related bloodstream infections in the observation group was 90.00% (54/60) for catheter outlet care and 91.67% (55/60) for maximizing sterile barrier, both higher than 70.37% (38/54) and 75.93% (41/54) in the control group, with statistical significance ( χ2=7.03, 5.30, both P<0.05); the total satisfaction rate of patients in the observation group was 92.91% (891/959), which was higher than 58.64% (577/984) in the control group, and the difference was statistically significant ( χ2=15.28, P<0.05). Conclusions:The implementation of BTS quality improvement model is helpful to improve the nursing quality of patients with indwelling NCC dialysis and improve the patient outcomes.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Radiation-induced heart disease(RIHD)is a cardiotoxic event secondary to radiotherapy for thoracic tumors,and has become another unfavorable factor affecting the health of cancer patients in addition to cancer cytotoxicity.Signal transduction plays an important role in cellular information exchange.RIHD can induce dysregulation of signaling pathways and hinder the normal function of pathways,thus causing myocardial tissue to undergo lesions such as apoptosis,oxidative stress and fibrosis.Now,we review the relevant pathways that are dysregulated in the development of RIHD,as well as the regulatory effects of drug intervention on these pathways,in order to provide a reference basis for the prevention and treatment of RIHD.