Effect of iTBS dual-target stimulation on lower limb function in patients with incomplete spinal cord injury:a randomized, single-blind,sham-controlled study.

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

Antineutrophil cytoplasmic antibody is an independent risk factor in rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: This study aimed to investigate the clinical relevance of antineutrophil cytoplasmic antibody (ANCA) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: Detailed clinical records of rheumatoid arthritis (RA) patients who underwent ANCA screening tests were collected. ANCA measurements were determined by indirect immunofluorescence assay (IIF) and enzyme-linked immunosorbent assay (ELISA). Clinical characteristics were compared between ANCA-positive and ANCA-negative groups, and multivariable logistic models were used to evaluate the independent association of ANCA with ILD in RA patients. RESULTS: The prevalence of ANCA by IIF was significantly higher in RA-ILD patients compared to those with RA without ILD (31.7 % vs. 19.5 %, p < 0.001). RA-ILD patients positive for ANCA exhibited elevated levels of inflammatory markers and greater disease activity, and showed more severe impairment of lung function compared to ANCA-negative RA-ILD patients. Multivariable logistic regression analysis revealed an independent association of ANCA, especially pANCA, with RA-ILD. ANCA specificities for BPI, elastase, and cathepsin-G were found in 15.6 % of RA-ILD patients; the specificities for most others remain unknown. CONCLUSIONS: The findings suggest a potential role for ANCA/pANCA in stratifying the risk of RA and provide supplementary information to the existing clinically available assays. This additional information may be valuable in identifying RA patients who require further investigations for RA-ILD, such as high-resolution computed tomography (HRCT). These results emphasize the potential clinical relevance of ANCA in the context of RA-ILD.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis.

Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

Tracing the vertical migration of exogenous cadmium in soil by seasonal freeze-thaw event using rare earth elements.

Environmental behaviors of heavy metal in soil are strongly influenced by seasonal freeze-thaw events at the mid-high altitudes. However, the potential impact mechanisms of freeze-thaw cycles on the vertical migration of heavy metal are still poor understood. This study aimed to explore how exogenous cadmium (Cd) migrated and remained in soil during the in-situ seasonal freeze-thaw action using rare earth elements (REEs) as tracers. As a comparison, soil which was incubated in the controlled laboratory (25 °C) was employed. Although there was no statistically significant difference in the Cd levels of different soil depths under different treatments, the original aggregate sources of Cd in the 5-10 cm and 10-15 cm soil layers differed. From the distributions of REEs in soil profile, it can be known that Cd in the subsurface of field incubated soil was mainly from the breakdown of >0.50 mm aggregates, while it was mainly from the <0.106 mm aggregates for the laboratory incubated soil. Furthermore, the dissolved and colloidal Cd concentrations were 0.47 µg L-1 and 0.62 µg L-1 in the leachates from field incubated soil than those from control soil (0.21 µg L-1 and 0.43 µg L-1). Additionally, the colloid-associated Cd in the leachate under field condition was mainly from the breakdown of >0.25 mm aggregates and the direct migration of <0.106 mm aggregates, while it was the breakdown of >0.50 mm and the direct migration of <0.106 mm aggregates for the soil under laboratory condition. Our results for the first time provided insights into the fate of exogenous contaminants in seasonal frozen regions using the rare earth element tracing method.

Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro.

SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63-linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL-0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50-fold and 7-fold (half maximal inhibitory concentration (IC50)) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon-ß (IFN-ß) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structure-activity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.

Identifying differentially expressed genes in goat mammary epithelial cells induced by overexpression of SOCS3 gene using RNA sequencing.

The suppressor of cytokine signaling 3 (SOCS3) is a key signaling molecule that regulates milk synthesis in dairy livestock. However, the molecular mechanism by which SOCS3 regulates lipid synthesis in goat milk remains unclear. This study aimed to screen for key downstream genes associated with lipid synthesis regulated by SOCS3 in goat mammary epithelial cells (GMECs) using RNA sequencing (RNA-seq). Goat SOCS3 overexpression vector (PC-SOCS3) and negative control (PCDNA3.1) were transfected into GMECs. Total RNA from cells after SOCS3 overexpression was used for RNA-seq, followed by differentially expressed gene (DEG) analysis, functional enrichment analysis, and network prediction. SOCS3 overexpression significantly inhibited the synthesis of triacylglycerol, total cholesterol, non-esterified fatty acids, and accumulated lipid droplets. In total, 430 DEGs were identified, including 226 downregulated and 204 upregulated genes, following SOCS3 overexpression. Functional annotation revealed that the DEGs were mainly associated with lipid metabolism, cell proliferation, and apoptosis. We found that the lipid synthesis-related genes, STAT2 and FOXO6, were downregulated. In addition, the proliferation-related genes BCL2, MMP11, and MMP13 were upregulated, and the apoptosis-related gene CD40 was downregulated. In conclusion, six DEGs were identified as key regulators of milk lipid synthesis following SOCS3 overexpression in GMECs. Our results provide new candidate genes and insights into the molecular mechanisms involved in milk lipid synthesis regulated by SOCS3 in goats.

Analysis of Clinical Outcome and Prognosis of C-reactive Protein Combined with Albumin in Patients with Acute Myocardial Infarction.

Objective: This study aims to assess the combined predictive value of C-reactive protein (CRP) and albumin (ALB) for major adverse cardiovascular events (MACE) post-percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: We analyzed data from continuously enrolled AMI patients who underwent emergency PCI at the First Affiliated Hospital of Xinjiang Medical University over six years, employing logistic regression to derive a predictive equation for in-hospital mortality and out-of-hospital MACE events. Primary endpoints: In-hospital death and out-of-hospital major adverse cardiovascular events. The patients were followed up for 1, 3, 6, and 12 months after discharge. The average follow-up time was 41 months. Results: Among the 601 patients studied, we observed 16 in-hospital deaths and 131 out-of-hospital MACE events. Multivariate logistic regression analysis showed that the independent predictors of out-of-hospital MACE events were age (OR=1.067, 95% CI 1.013-1.124, P = .028), C-reactive protein (OR=1.012, 95% CI 1.000-1.025, P = .045) and albumin (OR=0.874, 95% CI 0.785-0.973, P = .014). Our multivariate logistic regression analysis identified age, CRP, and albumin as independent predictors, with the combined equation yielding an ROC curve area of 0.85, effectively stratifying patients into high-risk and low-risk groups. Subsequent follow-up results validated this risk stratification approach. Conclusion: The study underscores the efficacy of combining CRP and albumin levels as a predictive measure for in-hospital death and out-of-hospital MACE events in AMI patients post-PCI.

Innovations in 3D printed individualized bone prosthesis materials: revolutionizing orthopedic surgery: a review.

The advent of personalized bone prosthesis materials and their integration into orthopedic surgery has made a profound impact, primarily as a result of the incorporation of three-dimensional (3D) printing technology. By leveraging digital models and additive manufacturing techniques, 3D printing enables the creation of customized, high-precision bone implants tailored to address complex anatomical variabilities and challenging bone defects. In this review, we highlight the significant progress in utilizing 3D printed prostheses across a wide range of orthopedic procedures, including pelvis, hip, knee, foot, ankle, spine surgeries, and bone tumor resections. The integration of 3D printing in preoperative planning, surgical navigation, and postoperative rehabilitation not only enhances treatment outcomes but also reduces surgical risks, accelerates recovery, and optimizes cost-effectiveness. Emphasizing the potential for personalized care and improved patient outcomes, this review underscores the pivotal role of 3D printed bone prosthesis materials in advancing orthopedic practice towards precision, efficiency, and patient-centric solutions. The evolving landscape of 3D printing in orthopedic surgery holds promise for revolutionizing treatment approaches, enhancing surgical outcomes, and ultimately improving the quality of care for orthopedic patients.

Identifying the needs of people with long COVID: a qualitative study in the UK.

OBJECTIVES: To identify the needs of people with long COVID (LC) in the UK. DESIGN: Qualitative study using the Framework Analysis to analyse focus group discussions. PARTICIPANTS: 25 adults with LC aged 19-76 years including 17 men and 8 women. Average disease duration was 80.1 weeks. SETTING: Eight focus groups were conducted in April 2023 online and in-person at the University of Leeds (UoL), UK. Recruitment routes included advertisement via Leeds Community Healthcare services, the English National Opera Breathe Programme and within the UoL. RESULTS: Three key themes/needs were identified. (Theme 1) Support systems including community groups, disability benefits, clinical services and employment support should be accessible and tailored to the needs of people with LC. (Theme 2) Research should investigate the physiology of symptoms, new clinical tests and treatment interventions to improve clinical understanding of the condition and symptom management. (Theme 3) Societal awareness should be promoted via local and national initiatives to educate the public about the condition and reduce stigma. CONCLUSIONS: Participants experienced varied and individual challenges to daily life due to LC. There is a need for government acknowledgement of LC as a disability to ensure people with LC have access to disability support and legal protection. Policy development should be patient-driven and acknowledge the individual needs of people with LC in order to improve their quality of life.

Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.

Coronavirus (CoV) infections have caused contagious and fatal respiratory diseases in humans worldwide. CoV 3-chymotrypsin-like proteases (3CLpro or Mpro) play an important role in viral maturation, and maintenance of their dimeric conformation is crucial for viral activity. Therefore, allosterically regulated dimerization of 3CLpro can be employed as a drug development target. Here, we investigated the allosteric regulatory mechanism of 3CLpro dimerization by using hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) technology. We found that the FLAG tag directly coupled to the N-finger of 3CLpro significantly increased HDX kinetics at the dimer interface, and 3CLpro transformed from a dimer to a monomer. The 3CLpro mutants of SARS-CoV-2, which are monomeric, also exhibited increased deuterium exchange. Binding of the allosteric inhibitor Gastrodenol to most betacoronavirus 3CLpros led to increased allosteric deuterium exchange, resulting in the monomeric conformation of the CoV 3CLpro upon binding. Molecular dynamics (MD) simulation analysis further indicated the molecular mechanism of action of Gastrodenol on CoV 3CLpro: binding of Gastrodenol to SARS-CoV-2 3CLpro destroyed the hydrogen bond in the dimer interface. These results suggest that Gastrodenol may be a potential broad-spectrum anti-betacoronavirus drug.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Potential convergence of olfactory dysfunction in Parkinson's disease and COVID-19: The role of neuroinflammation.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that affects 7-10 million individuals worldwide. A common early symptom of PD is olfactory dysfunction (OD), and more than 90% of PD patients suffer from OD. Recent studies have highlighted a high incidence of OD in patients with SARS-CoV-2 infection. This review investigates the potential convergence of OD in PD and COVID-19, particularly focusing on the mechanisms by which neuroinflammation contributes to OD and neurological events. Starting from our fundamental understanding of the olfactory bulb, we summarize the clinical features of OD and pathological features of the olfactory bulb from clinical cases and autopsy reports in PD patients. We then examine SARS-CoV-2-induced olfactory bulb neuropathology and OD and emphasize the SARS-CoV-2-induced neuroinflammatory cascades potentially leading to PD manifestations. By activating microglia and astrocytes, as well as facilitating the aggregation of α-synuclein, SARS-CoV-2 could contribute to the onset or exacerbation of PD. We also discuss the possible contributions of NF-κB, the NLRP3 inflammasome, and the JAK/STAT, p38 MAPK, TLR4, IL-6/JAK2/STAT3 and cGAS-STING signaling pathways. Although olfactory dysfunction in patients with COVID-19 may be reversible, it is challenging to restore OD in patients with PD. With the emergence of new SARS-CoV-2 variants and the recurrence of infections, we call for continued attention to the intersection between PD and SARS-CoV-2 infection, especially from the perspective of OD.

Yeast Prion Protein Sup35 Initiates α-Synuclein Pathology in Parkinson's Disease.

Sinus infection of Saccharomyces cerevisiae accelerates the aggregation of α-synuclein (α-syn) in A53T mice, which was caused by prion protein Sup35. Sup35 promotes α-syn aggregation in vitro and in vivo and leads to Parkinson's disease (PD)-like motor impairment in wildtype mice, suggesting that the yeast Sup35 triggers α-syn pathology in PD.

Systematic evaluation of vertebral bone quality score as an opportunistic screening method for BMD in spine surgery patients.

PURPOSE: This study aimed to evaluate and compare the predictive value of vertebral bone quality (VBQ) score for low BMD and osteoporosis. Furthermore, we sought to enhance diagnostic effectiveness by integrating VBQ with easily accessible patient-specific factors. METHODS: We retrospectively analyzed data from 180 patients. VBQ was obtained by preoperative MRI. Low BMD was classified as meeting the standards for either osteopenia or osteoporosis. The receiver operating characteristic curve analysis and multivariate logistic regression were used to detect the ability of variables to assess BMD. The z-test was used to compare the area under the curves of different variables. RESULTS: VBQ was more effective in identifying low BMD than osteoporosis (AUC, 0.768 vs. 0.613, p = 0.02). Elevated VBQ (OR 6.912, 95% CI 2.72-17.6) and low BMI (0.858, 0.76-0.97) were risk factors for low BMD, while the risk factor for osteoporosis was age (1.067, 1.02-1.12), not VBQ. ROC analysis showed that AUCs were 0.613 for VBQ and 0.665 for age when screening for osteoporosis. The combined variable of VBQ, sex, age, and BMI obtained by logistic regression significantly improved the efficacy of BMD screening, with an AUC of 0.824 for low BMD and 0.733 for osteoporosis. CONCLUSION: VBQ is better at detecting low BMD than identifying osteoporosis. The ability of VBQ to predict osteoporosis is limited, and a similar diagnostic efficacy can be achieved with age. Incorporating VBQ alongside demographic data enhances the efficiency of BMD assessment. With the development of artificial intelligence in medicine, this simple method is promising.

Application of gel based on medical image inspection in total closure resection of oral cancer patients.

Oral cancer is a common malignant tumor, and total closed resection is a common treatment. However, it has always been a challenge to determine the exact extent of excision during surgery. The application of medical image examination in surgery can provide important reference information, but the current methods still have some limitations. This study explored the application of gels based on medical image examination in the total closed resection of oral cancer patients to improve the accuracy of resection range and surgical treatment effect. The study collected medical image data of patients with oral cancer for image enhancement and determination of resection boundaries. By comparing the results of the experimental group and the control group, the application effect of gel in operation was evaluated. Through the application of medical image inspection technology, the determination of surgical resection boundary is more accurate, and the positive incisal margin of patients is effectively avoided. Gel technology improves the success rate and efficacy of surgery, and this method helps to improve the accuracy of surgery and the certainty of the scope of resection, which is of great significance for improving the surgical treatment effect and the survival rate of patients.

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

[Mechanism of traditional Chinese medicine in treating ulcerative colitis-related colorectal cancer by regulating NF-κB-related signaling pathways: a review].

Ulcerative colitis is a chronic, recurrent, and nonspecific intestinal inflammatory disease, which is difficult to cure and has the risk of deterioration into related tumors. Long-term chronic inflammatory stimulation can increase the risk of cancerization. With the signaling pathway as a key link in the regulation of tumor microenvironments, nuclear factor-kappa B(NF-κB) is an important regulator of intestinal inflammation. It can also be co-regulated as downstream factors of other signaling pathways, such as TLR4, MAPK, STAT, PI3K, and so on. At present, a large number of animal experiments have proved that traditional Chinese medicine(TCM) can reduce inflammation by interfering with NF-κB-related signaling pathways, improve intestinal inflammation, and inhibit the progression of inflammation to tumors. This article reviewed the relationship between NF-κB-related signaling pathways and the intervention mechanism of TCM, so as to provide a reference for the clinical treatment of ulcerative colitis and the optimization of related cancer prevention strategies.