Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

BACKGROUND:Polyurethane materials,with their outstanding physicochemical properties,present extensive opportunities in the realm of biomedical engineering.Biomimetic design and functional modification of polyurethane nerve conduits are expected to further address the challenges of nerve regeneration and repair.OBJECTIVE:To review the current status and advancements in the application of polyurethane-based nerve conduits in the field of peripheral nerve repair.METHODS:The Chinese and English search terms consisted of"polyurethane,PU,polyurethane material,polyurethane biomaterials,nerve regeneration,peripheral nerve injury,nerve repair,nerve scaffold,nerve guidance conduit,nerve conduits."The search was conducted in databases such as PubMed,Web of Science,CNKI(China National Knowledge Infrastructure),and WanFang for articles published from 2014 to 2024.Finally,61 articles were included in the review.RESULTS AND CONCLUSION:Biomimetic composition is an effective strategy for enhancing the biological activity of polyurethane nerve conduits.Through structural biomimicry,polyurethane nerve conduits can be optimized to provide biological guidance cues for neural tissue regeneration.The biomechanically biomimetic polyurethane nerve conduits are likely to play a significant role in immune modulation and the promotion of axonal growth.By optimizing the conductive microenvironment of polyurethane materials,the reconstruction of neural electrical signal pathways can be facilitated.Polyurethane nerve conduits can serve as drug carriers,exerting anti-inflammatory and neuroprotective effects.Although the combined application of multiple design strategies can improve various aspects of damaged nerve function,the complex structure and dynamically changing pathophysiological microenvironment of nerves mean that nerve conduit design strategies still require refinement.Future advancements and innovations in nerve biomimetic design strategies hold promise for providing new insights and opportunities in the field of neural tissue engineering.

BACKGROUND:Polyurethane materials,with their outstanding physicochemical properties,present extensive opportunities in the realm of biomedical engineering.Biomimetic design and functional modification of polyurethane nerve conduits are expected to further address the challenges of nerve regeneration and repair.OBJECTIVE:To review the current status and advancements in the application of polyurethane-based nerve conduits in the field of peripheral nerve repair.METHODS:The Chinese and English search terms consisted of"polyurethane,PU,polyurethane material,polyurethane biomaterials,nerve regeneration,peripheral nerve injury,nerve repair,nerve scaffold,nerve guidance conduit,nerve conduits."The search was conducted in databases such as PubMed,Web of Science,CNKI(China National Knowledge Infrastructure),and WanFang for articles published from 2014 to 2024.Finally,61 articles were included in the review.RESULTS AND CONCLUSION:Biomimetic composition is an effective strategy for enhancing the biological activity of polyurethane nerve conduits.Through structural biomimicry,polyurethane nerve conduits can be optimized to provide biological guidance cues for neural tissue regeneration.The biomechanically biomimetic polyurethane nerve conduits are likely to play a significant role in immune modulation and the promotion of axonal growth.By optimizing the conductive microenvironment of polyurethane materials,the reconstruction of neural electrical signal pathways can be facilitated.Polyurethane nerve conduits can serve as drug carriers,exerting anti-inflammatory and neuroprotective effects.Although the combined application of multiple design strategies can improve various aspects of damaged nerve function,the complex structure and dynamically changing pathophysiological microenvironment of nerves mean that nerve conduit design strategies still require refinement.Future advancements and innovations in nerve biomimetic design strategies hold promise for providing new insights and opportunities in the field of neural tissue engineering.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS^E） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg^-1·d^-1） or AAⅠ（5 mg·kg^-1·d^-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C₁₈ column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L^-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min^-1. Positive ion mode of electrospray ionization（ESI⁺） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MS^E was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

New-onset refractory status epilepticus is a rare and special clinical manifestation with high mortality. About half of the patients have no clear cause. At present, the pathogenesis is unclear, and the treatment plan is controversial. In recent years, it has been found that inflammatory and immune responses of the body may be involved in the pathogenic process, and it is called “inflammatory-immune mediated epileptic encephalopathy” based on the perspective of pathogenesis. There have also been many treatment attempts based on the inflammatory and immunological mechanisms, some of which have achieved satisfactory results. However, most of them are based on the review of small sample cases, and relevant guidelines are still lacking at present. In this paper, the definition, etiology, pathogenesis, clinical manifestations and treatment of persistent status of new-onset refractory status epilepticus are reviewed.

Anti-contactin associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis with variable clinical symptoms and atypical imaging manifestations. The prognosis of the patients with severe disease is poor. Reversible posterior leukoencephalopathy syndrome is rarely reported in autoimmune encephalitis. The clinical data, diagnosis and treatment of a patient with anti-CASPR2 antibody encephalitis complicated with reversible posterior encephalopathy syndrome were reported, in order to improve the understanding of clinicians on the rare disease complicated with atypical imaging manifestations.

Objective To analyze the neuroelectrophysiological characteristics of peripheral neuropathy after chronic obstructive pulmonary disease. Methods From January to December, 2016, a total of 60 patients of chronic obstructive pulmonary disease with peripheral neuropathy were reviewed the motor conduction velocity and compound muscle action potential amplitude of median, ulnar, tibial, peroneal nerves; the sensory conduction velocity and sensory nerve action potential amplitude of median, ulnar, tibial, superficial peroneal nerves; and the skin sympathetic response of limbs. Results The incidence of abnormalities was higher in amplitude than in conduction velocity of motor nerve and sensory nerves (χ2=190.026, P<0.001). The incidence of abnormal conduction velocity was similar in motor nerve and sensory nerves (χ2=1.538, P>0.05), as well as the abnormal action potential amplitude (χ2=2.839, P>0.05). The incidence of abnormal conduction was similar with abnormal skin sympathetic response (χ2=0.001, P>0.05). The incidence of abnormalities of nerve conduction study (χ2=81.114, P<0.001) and abnormal skin sympathetic response (χ2=5.689, P<0.05) was more in lower limbs than in upper limbs. Conclusion The peripheral neuropathy after chronic obstructive pulmonary disease characters mainly as motor-sensory multiple neuropathy, involving motor, sensory and autonomic nerve. The axonal damage is significant, with the similar severity between motor and sensory nerves, as well as between the large and small nerves.

Objective To explore the activition and polarization of microglia in the epileptic rats induced by lithium chloride-pilocarpine. Methods One hundred male SD rats were randomly divided into five groups: control group and different time points model groups including 1d,3d,7d and 14d. Epilepsy models were established by lithium chloride-pilocarpine intraperitoneal injection. The control group was given the same dosage of normal saline. The morphology change was detected by immunofluorescence,and the expressions of iNOS and Arg-1 were determined by IHC at respective time points. Results Compared the model groups with control group,microglia was activated,synapsis was shorten,volume got bigger,most of them seemed as amoebocyte,the expression of iNOS increased and Arg-1 decreased,especially at 3d.ConclusionThe results from this study indicated that microglia was activated and polarized in epileptic rats induced by pilocarpine.