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

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Post-orgasmic illness syndrome (POIS) is a rare condition characterized by the rapid onset of extreme fatigue, flu-like symptoms, difficulty concentrating, depression, nasal congestion, rhinorrhea, itchy eyes, and other physical and psychological discomforts following ejaculation. This report presents the outcomes of two patients with POIS who underwent a two-year course of autologous seminal plasma subcutaneous cluster immunotherapy. Treatment efficacy was assessed using methods such as the symptom Visual Analogue Scale (VAS), the Union Physio-Psycho-Social Assessment Questionnaire (UPPSAQ)-70, and the Short Form 36 Health Survey (SF-36). The results suggest that autologous seminal plasma subcutaneous cluster immunother-apy may be a safe and effective therapeutic approach for POIS.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

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.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

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.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.