Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Filamentous fungi represent an important group of eukaryotic microorganisms with diverse ecological functions and ubiquitous distribution in various ecosystems. Among them, many species are closely associated with agriculture, functioning as major plant pathogens that cause yield losses and produce mycotoxins to compromise both the quality and safety of agricultural products. In recent years, the CRISPR/Cas system has emerged as a powerful and programmable genome editing tool, and it has been extensively applied to the genetic study of plant pathogenic fungi. This technology has greatly facilitated the investigation of pathogenic mechanisms, mycotoxin biosynthetic pathways and key gene functions, antifungal resistance, and rapid pathogen detection. This review summarizes the development of CRISPR/Cas systems and the key strategies for their application in plant pathogenic fungi and makes an outlook on the practical deployment. With the continuous advancement of gene editing technologies, emerging fungal-adapted editing systems hold great promise for advancing functional genomics and enabling innovations in disease-resistant breeding and sustainable crop protection.
Gene Editing/methods* ; Fungi/pathogenicity* ; CRISPR-Cas Systems/genetics* ; Plant Diseases/microbiology* ; Plants/microbiology* ; Genome, Fungal/genetics*

OBJECTIVE To investigate the prognostic factors of chondrosarcoma of the larynx,deeply analyze its clinical data,and provide a theoretical basis for better treatment of chondrosarcoma of the larynx.METHODS A retrospective analysis was conducted on the complete clinical data of patients with primary chondrosarcoma of the larynx admitted to the Department of Otolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University from January 2010 to December 2024.RESULTS A total of 15 patients were included,including 11 males and 4 females,with a gender ratio of 11∶4.The average age of onset was 57.3 years,and the average clinical symptom duration was 12.2 months.The tumors were mainly located in the cricoid cartilage in 11 patients,in the arytenoid cartilage in 2 patients,and in the thyroid cartilage in 2 patients.Tumor grading showed that 7 patients were grade I and 8 were grade II.Four patients underwent transoral laser minimally invasive surgery,2 patients underwent partial laryngectomy+tracheotomy,and 9 patients underwent total laryngectomy/cervical lymph node dissection+tracheostomy.The 5-year overall survival rate was 85.7%,the 5-year disease-specific survival rate was 100%,and the 5-year local-regional control rate was 90.9%.Gender,tumor location,tumor grade,Ki-67,tumor size,and whether larynx preservation surgery was performed did not affect the local-regional control rate or disease-specific survival rate.CONCLUSION Laryngeal chondrosarcoma generally has a longer disease history and is difficult to detect.The pathological type is mostly well-differentiated.Regional or distant metastasis is rare,and the long-term survival rate is good.Surgical resection is the preferred treatment option.On the basis of not reducing the tumor control rate,surgery that prioritizes preserving laryngeal function should be given priority,while comprehensive treatment is generally not recommended.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

We report a case of anti-IgLON5 disease with a motor neuron disease-like presentation admitted to the Department of Neurology, Xuanwu Hospital, Capital Medical University in July 2021. The patient was a 71-year-old female who presented with the chief complaint of limb weakness persisting for 4 months. She showed progressive limb weakness accompanied by muscle atrophy. Electromyography (EMG) revealed extensive neurogenic damage. Initial serum evaluation for neural-specific autoantibodies was positive for IgLON5-Ab (1∶100). Repeat testing confirmed IgLON5-Ab positivity with a titer of 1∶1 000. The patient was diagnosed with anti-IgLON5 disease and treated with methylprednisolone and immunoglobulin, leading to clinical improvement. We found four relevant articles reporting a total of 11 similar cases. Thus, in this study, we analyzed a total of 12 cases, including our patient. Based on their clinical manifestations, these cases can be categorized into two types: amyotrophic lateral sclerosis(ALS)type and isolated bulbar type. Six cases—three males and three females—presented with the ALS type. Of these, three cases had diffuse limb weakness accompanied by muscle atrophy(two cases had diffuse hyperreflexia and one had a normal tendon reflex); one case presented with neck extensor weakness and bilateral asymmetric upper extremity weakness and was hyperreflexic at the bilateral patellar tendons; one case displayed asymmetric weakness in both lower limbs with normal deep reflexes, and one case exhibited neck weakness with hyperreflexia. EMG revealed diffuse lower motor neuron disease involving two or three regions. All patients tested positive for serum anti-IgLON5 antibodies. Four were also positive for anti-IgLON5 antibodies in cerebrospinal fluid, two were negative, and six were not tested. Among the 11 patients who received immunotherapy, 4 showed partial improvement in clinical symptoms, 2 exhibited transient improvement, 2 remained stable, and 3 showed no improvement. Testing for IgLON5-Ab should be considered among patients presenting with bulbar symptoms or ALS-like features, especially those with acute or subacute onset, rapid progression, autonomic dysfunction, vocal cord paralysis requiring tracheotomy, cognitive impairment, or involuntary movements. Early diagnosis and treatment may improve clinical symptoms and reduce adverse outcomes.

Objective:To improve the understanding of the clinical manifestation of immunoglobulin G 4-related disease (IgG 4-RD) with neurological involvement. Methods:Patients presenting with neurological symptoms and biopsy-confirmed IgG 4-RD were enrolled between March 2014 and March 2024 from the Department of Neurology of Xuanwu Hospital of Capital Medical University. Medical record data of all patients were retrospectively reviewed, including clinical manifestations, laboratory findings, radiological results, pathology, treatments, and outcomes. RD were enrolled between March Results:Nine patients (five males, four females; median age at onset: 63 years) were included in the study. Neurological manifestations consisted of pachymeningitis in six cases, peripheral nerve involvement in two, and brain parenchyma involvement in one. Four patients displayed isolated neurologic symptoms. The most common clinical manifestations were headache and cranial nerve palsy, each involving five cases. Magnetic resonance imaging showed thickening and enhancement of the dura mater in the six patients with pachymeningitis. Four of these cases involved the posterior cranial fossa, 3 presented with an inflammatory pseudotumor, and 2 involved the spinal cord. Four patients with pachymeningitis had normal serum IgG 4 concentrations. Eight patients exhibited elevated serum C-reactive protein or erythrocyte sedimentation rates, with some also showing decreased complement C3 and C4 levels. Cerebrospinal fluid immunoglobulin was elevated in all nine cases. In all cases, histopathologic biopsy results showed extensive infiltration of lymphocytes and plasma cells, with the latter displaying IgG 4+abnormalities. All patients received glucocorticoid therapy, with six also receiving immunosuppressants. All patients were followed up for a median of 30 months, with outcomes including two complete remissions, five partial remissions, one unchanged condition, and one death. Six patients experienced a relapse. Conclusions:Isolated hypertrophic pachymeningitis is the most common manifestation of IgG 4-RD, often occurring in the absence of elevated serum IgG 4 levels. Peripheral nerve and brain parenchyma involvement can also be seen. Clinical manifestations are non-specific, and histopathologic biopsy is frequently required for diagnosis. Although the disease responds well to hormone treatment, recurrence is common. Early combined immunosuppressive therapy can improve prognosis.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.