This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Objective To investigate CBX2 and TIM3 in salivary adenoid cystic carcinoma(SACC)tissue and their relationship with clinical pathological features and prognosis.Methods 80 patients with SACC who underwent surgical treatment in the First Affiliated Hospital of Hebei North University from January 2016 to January 2020 were selected.Immunohistochemistry was used to measure CBX2 and TIM3 in tissues.The relationship between CBX2 and TIM3 in SACC tissue and prognosis was discussed though Kaplan-Meier method.The factors influencing the prognosis of SACC were discussed using multivariate Cox regression.Results The positive rates of CBX2 and TIM3 in SACC tissues were clearly higher than those in normal glandular tissues adjacent to cancer(χ2=11.237,8.229,P<0.05).The CBX2 and TIM3 were associated with nerve invasion and distant metastasis(P<0.05).After a 5-year follow-up,26 cases died and 54 cases survived,with an overall 5-year survival rate of 67.50%(54/80).The death group had higher positive rates of CBX2 and TIM3 in SACC tissues than the survival group(P<0.05).Patients with positive CBX2 and TIM3 in SACC tissues had clearly lower 5-year survival rate than patients with negative CBX2 and TIM3(Log Rank χ2=6.564,5.197,P<0.05).CBX2,TIM3 positivity,nerve invasion,and distant metastasis were risk factors affecting prognosis(P<0.05).Conclusion The positive expression of CBX2 and TIM3 in SACC tissues is closely related to the clinical pathological features and prognosis of patients.

The radiation-free and unmarked body surface monitoring technology is developed for reducing the additional radiation dose generated by positioning error verification during radiotherapy positioning,and further reducing the positioning error and monitoring the displacement deviation of patients during radiotherapy in real time.At present,the widely used optical surface guided radiotherapy technology is also a type of radiotherapy guided by body surface monitoring.The system mainly uses optical imaging equipment as a tool to complete body surface scanning,three-dimensional reconstruction,real-time monitoring,etc.,thereby assisting doctors to carry out radiotherapy more accurately.Herein the study elaborates on the methods,technologies and research results of guided radiotherapy from the aspects of body surface markers,three-dimensional surface imaging systems and mobile devices,and provides prospects for future researches.

Objective:To investigate the clinical features, imaging characteristics, surgical strategies, and therapeutic outcomes of otitis media complicated with inflammatory response of local meninges.Methods:A retrospective analysis was conducted on the clinical data of 8 patients with chronic suppurative otitis media complicated with inflammatory response of local meninges, treated by the Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital from 2019 to 2023. Appropriate surgical strategies were selected based on the patient′s clinical manifestations, imaging characteristics, extent of lesions, and facial nerve function. Follow-up was performed postoperatively to assess the therapeutic outcomes.Results:Among the eight patients, there were six males and two females, with an average age of (55.9±12.6) years old. The primary clinical manifestations included otorrhea, hearing loss, facial paralysis, earache, headache, and fever. All patients had a history of chronic suppurative otitis media and tympanic membrane perforation, with varying degrees and types of hearing loss. Seven patients presented with peripheral facial palsy preoperatively, with the House-Brackmann (H-B) grading scale as follows: 4 cases (4/7) in grade Ⅳ, 1 case (1/7) in grade Ⅴ, and 2 cases (2/7) in grade Ⅵ. The mean duration of otorrhea and/or hearing loss was (24.68±12.18) years, while, the average duration of severe headache, aggravated otorrhea and facial paralysis was (2.73±3.92) months. Preoperative high-resolution CT scan of the temporal bone revealed soft tissue shadow in the middle ear and mastoid process, with partial defects in the mastoid cortex. Cranial MRI T1WI showed high signal in the meninges on the affected side, with contrast-enhanced MRI indicating localized meningeal thickening. Four patients (4/8) had diabetes mellitus, and 2 patients (2/8) had a history of middle ear/mastoid surgery. All patients underwent surgical treatment, including thorough removal of lesions, adequate drainage, and facial nerve decompression. Tympanoplasty and hearing reconstruction were performed when conditions permitted. Specifically, 5 patients underwent intact canal wall radical mastoidectomy with facial nerve decompression and tympanoplasty, 2 patients underwent canal wall down mastoidectomy with facial nerve exploration decompression, and 1 patient underwent modified radical mastoidectomy. Postoperatively, patients experienced significant relief and gradual disappearance of ear and head pain. The postoperative H-B grading scale of facial nerve function was as follows: 4 cases in grade Ⅰ (4/8, including 1 case without preoperatively facial palsy), 2 cases (2/8) in grade Ⅱ, and 2 cases (2/8) in grade Ⅲ. Postoperative cranial MRI showed a significant reduction in localized meningeal thickening on the affected side.Conclusions:Patients with long-term chronic suppurative otitis media and/or cholesteatoma who suddenly presented with headache, fever, aggravated otorrhea, and facial paralysis should be suspected of having inflammatory response of local meninges. High-resolution CT of temporal bone and cranial MRI provide crucial diagnostic information. Early surgical exploration and thorough lesion removal are effective treatment methods.

Objective To explore the home rehabilitation experience of individuals with fully magnetically levitated left ventricular assist device,and to provide a basis for developing scientific nursing intervention plans and follow-up strategies for clinical practice.Methods Using phenomenological research methods,a semi-structured interview was conducted on 13 patients with fully maglev left ventricular assist device implantation in a tertiary A comprehensive hospital in Wuhan from September to October 2022.Colaizzi's 7-step analysis method was used to analyze the data and extract themes.Results A total of 3 themes and 9 subthemes were extracted,including complex emotions in home rehabilitation(challenges for new characters,anxieties and concerns,regaining new life and full of confidence),difficulties in home self-management(lack of professional knowledge,insufficient exercise,difficulty in managing pump cable bag wounds,weak ability to recognize and respond to external controller alarms),and needs for home rehabilitation(need for continuity of care,desire for more social support).Conclusion Complex emotional experiences and many difficulties and needs exist in the home rehabilitation process of patients after implantation of full magnetic levitation left ventricular assist device.Healthcare professionals should actively pay attention to the postoperative psychological changes of patients,strengthen pre-discharge training to improve patients'self-management ability,and actively build a multi-party Internet home rehabilitation management platform to improve the rehabilitation quality of patients.

Objective To investigate the effect of lung lobe surface projection localization combined with lung segment drainage sputum technique on airway clearance in patients with aspiration pneumonia,providing a reference for clinical nursing practice.Methods A convenience sampling method was used to select 62 patients with perioperative aspiration pneumonia secondary to brain diseases admitted to a tertiary A hospital in Beijing from May 2022 to October 2024 as the research subjects.A total of 31 patients admitted from August 2023 to October 2024 were assigned to a control group,and 31 patients admitted from May 2022 to July 2023 were assigned to an experimental group.The experimental group received lung lobe surface projection positioning combined with lung segment drainage sputum technique on top of conventional back percussion sputum clearance technique,while the control group received conventional back percussion sputum clearance technique.After the intervention,the differences in oxygenation state,inflammatory test indicators,treatment efficiency,vital signs and frequency of suction coughing between 2 groups were compared.Results After the intervention,the experimental group showed better oxygenation index,frequency of suction coughing,white blood cell count,percentage of neutrophils,procalcitonin levels,interleukin-6 levels,and treatment efficiency compared to those in the control group(P＜0.05).There was no statistically significant difference in heart rate,respiratory rate,and C-reactive protein levels between 2 groups(P＞0.05).Conclusion Lung lobe surface projection positioning combined can effectively promote the patients with aspiration pneumonia of loosening of sputum in the lungs,improve airway clearance efficiency,enhance the patient's pulmonary ventilation and gas exchange capacity,improve oxygenation levels,and reduce systemic inflammatory levels.

Objective:To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. Methods:A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children′s Hospital in June 2024 due to " intermittent convulsions for 13 days" . Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords " CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (Ethics No. HCHLL-2024-351). Results:① The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T 2 signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. ② Whole exome sequencing revealed a homozygous c. 2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+ PM3_Supporting+ PM2_Supporting). ③ A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c. 61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had the onset of the disease before the age of one, of which two had epileptic seizures as the initial symptom. Conclusion:The homozygous variant CLCN2: c. 2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.

Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.