The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases. Biliary stricture is a rare but serious long-term complication of acute pancreatitis, which can induce cholangitis, progressive liver function impairment, and secondary biliary cirrhosis. Due to the clinical symptoms of acute pancreatitis that can mask biliary system diseases, some patients may not receive timely diagnosis and treatment for concurrent biliary issues during the onset of acute pancreatitis, which can be life-threatening in severe cases. Currently, the ideal treatment strategy for biliary system complications secondary to acute pancreatitis remains unclear, lacking definitive guidelines or consensus. This article integrates recent research developments from both domestic and international studies to elucidate the pathogenesis, diagnosis, and treatment strategies for biliary system complications secondary to acute pancreatitis.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective To analyze the clinical phenotypes and genetic variants of three families with NOG-re-lated symphalangism spectrum disorder(NOG-SSD).Methods Clinical data of 11 family members from three NOG-SSD families were retrospectively analyzed,including medical history,physical examination,imaging studies,and audiological evaluations.Genomic DNA was extracted from peripheral blood samples of family members for whole-exome sequencing.Results Among the 11 family members,four exhibited mixed or conductive hearing loss.Probands from family 1 and 2 presented with mixed hearing loss,proximal symphalangism,flexion impairment of the fifth interphalangeal joint,and absence of skin creases.The proband and her mother in family 3 displayed con-ductive/mixed hearing loss,proximal symphalangism,and characteristic facial features(semicylindrical nose,hypo-plastic alae nasi,and thin upper lip with vermilion border).Whole-exome sequencing identified pathogenic variants in the NOG gene(NM_005450.6)in all three families.Family 1 and 2 harbored the novel missense variant c.236T＞A(p.Met79Lys)and nonsense variant c.666C＞G(p.Tyr222Ter),respectively,while family 3 carried the frameshift variant c.31del(p.Leu11SerfsTer51).All three variants were classified as pathogenic or likely pathogen-ic and have not been previously reported.Patients in family 1 and 2 were diagnosed with proximal symphalangism-1(SYM 1),whereas those in family 3 were diagnosed with multiple synostoses syndrome-1(SYNS1).Conclusion The NOG gene variants c.236T＞A,c.666C＞G,and c.31del are causative for NOG-SSD in these three families.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.

Pediatric urological non-Hodgkin lymphoma is relatively rare.When a single renal or ureteral tumor with multiple lymph node or bone metastases is present, it is very easy to be misdiagnosed as urinary tumor with metastasis, resulting in unnecessary radical nephrectomy. This paper reports two cases of non-Hodgkin lymphoma presenting with single urinary nodules. Case 1 was diagnosed with a 4.5cm tumor in the right kidney due to fever and fatigue. CT and PET-CT showed multiple bone destruction and lymph node metastasis. Renal biopsy was performed and ALK-positive anaplastic large cell lymphoma was diagnosed. Chemotherapy was effective for 6 months. Case 2 was diagnosed with left hydronephrosis due to intermittent low back pain for 2 weeks. Ultrasound examination revealed ureteral dilation with left hydronephrosis and low echo occupying of the lower ureter. The patient had sudden blurred vision before surgery. MRI examination revealed space occupying in the right optic nerve frame, and PET-CT found multiple bone, lymph nodes and nerve invasion. A lymph node biopsy was performed and Burkitt lymphoma was diagnosed. After 6 months of chemotherapy and radiotherapy, the tumor shrank significantly.

Objective To systematically evaluate the incidence and influencing factors of axillary web syndrome(AWS)in postoperative breast cancer patients,and to provide evidence for reducing the incidence of axillary web syndrome.Methods A computer search was performed in China National Knowledge Infrastructure(CNKI),VIP,Wanfang,SinoMed,PubMed,Medline,Scopus,The Cochrane Library,Web of Science,Embase,searched for articles on AWS influencing factors of breast cancer published from the establishment of the database to January 6th,2025.The articles were screened according to the inclusion and exclusion criteria.Revman5.4 and Stata17.0 were used for systematic review.Results Fifteen studies involving 3979 breast cancer patients and 1 156 patients with AWS were included.The results of the Meta-analysis showed that there was significant statistical heterogeneity among the included studies(I2=97.0%,P<0.0001).Using the random effects model,the incidence of AWS was 32.2%[95%CI(0.24,0.40),P<0.0001].The influencing factors for AWS after breast cancer surgery are age,body mass index(BMI),total mastectomy,lymph node metastasis,and neoadjuvant chemotherapy.NAC),axillary lymph node dissection(ALND),and the number of harvested axillary lymph nodes.Conclusion The incidence of AWS after breast cancer surgery was high.Clinicians should give early nursing to the influencing factors,reduce the incidence of AWS and improve patients'quality of life after surgery.

Objective:To investigate the effect of Gexia Zhuyu decoction on Toll-like receptor 4 (TLR4)/Nuclear factor-kappaB (NF-κB) signaling pathway on ulcerative colitis and intestinal mucosal barrier.Methods:A total of 86 cases of ulcerative colitis admitted to Xi′an Traditional Chinese Medicine (TCM) Hospital from March 2019 to July 2023 were prospectively included and divided into observation group and control group according to random number table method, with 43 cases in each group. The control group was treated with mesalazine enteric-coated tablets; The observation group was treated with mesalazine enteric-coated tablets combined with Gexia Zhuyu decoction for removing stasis. The clinical efficacy of the two groups was compared in terms of TCM syndrome score, intestinal mucosal barrier function index [diamine oxidase (DAO), D-lactic acid (D-LA)], TLR4/NF-κB signaling pathway expression and inflammatory factor index [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] before and after treatment. The occurrence of adverse reactions was also compared.Results:The total effective rate of observation group was higher than that of control group (χ 2=4.074, P=0.044). Before treatment, there was no significant difference in TCM syndrome scores between the two groups (all P>0.05). After treatment, the TCM syndrome scores of both groups were lower than those before treatment (all P<0.05), and the TCM syndrome scores of the observation group were lower than those of the control group (all P<0.05). Before treatment, there were no significant differences in D-LA and DAO levels between the two groups (all P>0.05). After treatment, the levels of D-LA and DAO in both groups were lower than before treatment (all P<0.05), and the levels of D-LA and DAO in the observation group were lower than those in the control group (all P<0.05). After treatment, the mRNA expressions of TLR4 and NF-κB in both groups were decreased compared with those before treatment, and the mRNA expressions of TLR4 and NF-κB in the observation group were lower than those in the control group (all P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were decreased compared with those before treatment (all P<0.05), and the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ 2=2.346, P=0.126). Conclusions:The application of Gexia Zhuyu decoction in the treatment of ulcerative colitis can not only effectively improve the clinical symptoms, signs and intestinal mucosal barrier function, but also improve the inflammatory response by mediating TLR4/NF-κB signaling pathway.

Objective To conduct a multidimensional and multi-level evaluation of the comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus.Methods Based on the National Essential Medicines List(2018 Edition),dapagliflozin was selected as the control.A comprehensive clinical evaluation index system was established through literature review,focus group interviews and in-depth expert interviews,encompassing six dimensions:safety,efficacy,economy,suitability,innovation,and accessibility.The Delphi method and hierarchical direct weighting method were used to screen indicators and determine their weights.Evidence for each indicator was collected and integrated both qualitatively and quantitatively through literature research,real-world studies,and pharmacoeconomic evaluations.Experts scored the indicators based on the collected evidence,and a total score for the comprehensive clinical evaluation of empagliflozin was calculated by combining these scores with indicator weights,followed by a comparative analysis with dapagliflozin.Results A comprehensive clinical evaluation of empagliflozin in the treatment of type 2 diabetes mellitus was successfully established,consisting of 6 primary indicators,14 secondary indicators,and 41 tertiary indicators.The overall evaluation score for empagliflozin was 90.35,and 89.47 for dapagliflozin.Conclusion The comprehensive clinical value of empagliflozin in the treatment of type 2 diabetes mellitus is slightly higher than that of dapagliflozin.This finding can serve as a reference for rational clinical drug use and related decision-making.