Alzheimer's disease is a neurocognitive disorder and one of the contributing factors to dementia. According to the World Health Organization, this disease has a sig-nificant impact on the global population's health, with the number of affected individuals steadily increasing each year. Amidst rapid technological development, the use of artificial intelligence has significantly expanded into the field of medical diagnostics, encompassing areas such as the analysis of medical images, drug development, design of personalized treatment plans, and disease prediction and treatment. Deep learning, which is an important branch in the field of artificial intelligence, is playing a key role in solving several medical challenges by providing important technical support for the early detection, diagnosis, and treatment of Alzheimer's disease. Given this context, this review aims to explore the differences between conventional methods and artificial intelligence techniques in Alzheimer's disease research. Additionally, it aims to summarize current non-invasive and portable techniques for detection of Alzheimer's disease, offering support and guidance for the future prediction and management of the disease.

This study aimed to determine the challenges that cause a delay in the diagnosis of Japanese patients with specific intractable diseases by means of a survey. We conducted a questionnaire survey involving 424 patients with 12 specific intractable diseases. Pearson's chi-square test was used to examine the relationship between diagnostic delay and each factor. The reasons for the diagnostic delay were analyzed. Pearson's chi-square test showed statistically significant differences in the relationship between the period to definitive diagnosis and period between symptom onset and first hospital visit (p = 0.002), and the period when the patients suspected the disease (p < 0.001). Reasons for diagnostic delay of these patients were patients' time constraints, problem in access to medical institutions, hesitancy in seeking medical attention, and healthcare system issues. Early definitive diagnosis of intractable diseases was hindered by several important issues. The resolution of these issues will require combined societal efforts as well as improvements in the healthcare system. The study revealed the need for improving patients' awareness about their disease, enabling patients to be proactive towards achieving a definitive diagnosis, and making improvements in the healthcare system regarding early diagnosis and care of patients with intractable diseases.

Circular RNAs (circRNAs) are emerging as important regulators in human disease, but their function in osteoporosis (OP) is not sufficiently known. The aim of this study was to identify the possible molecular mechanism of circ_KIAA0922 in osteogenic differentiation of Saos-2 cells in vitro and the interactions among circ_KIAA0922, miR-148a-3p, and SMAD family member 5 (SMAD5). Circ_KIAA0922, miR-148a-3p, and SMAD5 were overexpressed by transient transfection. Dual-luciferase reporter assay system was used to analyze the combination among circ_KIAA0922, miR-148a-3p, and SMAD5. In addition, the levels of circ_KIAA0922, miR-148a-3p, SMAD5, osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) were detected using RT-qPCR or western blot analysis. Alizarin red staining was performed to analyze the degree of osteogenic differentiation under the control of circ_KIAA0922, miR-148a-3p, and SMAD5. We found that circ_KIAA0922 knockdown inhibited the proliferation and osteogenic differentiation of Saos-2 cells. Circ_KIAA0922 directly targeted miR-148a-3p, and miR-148a-3p inhibition reversed the effects of circ_KIAA0922 knockdown on the proliferation and osteogenic differentiation of Saos-2 cells. Overexpression of SMAD5 promoted the proliferation and osteogenic differentiation of Saos-2 cells and attenuated the inhibitory effect of miR-148a-3p on cell proliferation and osteogenic differentiation. In conclusion, circ_KIAA0922 facilitated Saos-2 cell proliferation and osteogenic differentiation via the circ_KIAA0922/miR-148a-3p/ SMAD5 axes in vitro, thus providing insights into the mechanism of osteogenic differentiation by circ_ KIAA0922.

Developmental and epileptic encephalopathy 45 (DEE45) is an autosomal dominant disease caused by variation in the gamma-aminobutyric acid type A receptor subunit beta 1 (GABRB1) gene. Affected individuals have severely impaired intellectual development, hypotonia, and other persistent neurological deficits. However, DEE45 is rare; only four infants with DEE45 have been reported worldwide and no case has been reported in China. Confirming a diagnosis of DEE45 is of great significance for guiding further treatment, assessing patient prognosis, and genetic counseling. The clinical characteristics of DEE45 and the medical history of DEE45 patients requires supplementation and clarification. Here, we present the clinical and genetic findings of a 7-year-old girl with DEE45 carrying a novel de novo GABRB1 mutation (c.858_859delinsTT, p.286_287delinsIleSer) identified by whole exome sequencing (WES). The mutation is phylogenetic conserved in the second helix of the β1-subunit's transmembrane region. Western blot and RT-qPCR both indicated significant increase in the expression levels of GABRB1 mutant when compared with wild. The proband has epileptic encephalopathy and experienced refractory epilepsy onset at age 2 months and showed developmental delay at age 8 months. Electroencephalography (EEG) displayed hypsarrhythmia. Magnetic resonance imaging (MRI) showed no significant abnormalities in the internal structure of the patient's brain, which is displayed in two previously reported cases. The patient's symptoms of hypotonia, ataxia, profound mental retardation, and dysmetria became evident with development. In summary, we report the genetic and clinical characteristics of the first Chinese patient with DEE45 and explores the relationship between mutation and clinical symptoms.

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNAs. piRNAs derive from an initial transcript encompassing a piRNA cluster via a unique biosynthesis process, interact with PIWI proteins, bind to specific targets, and recruit chromatin modifiers to enable transcriptional repression. Abnormal expression of PIWI proteins and piRNAs has been reported in some human cancers, with participation of some PIWI/piRNAs complexes in tumorigenesis and association with cancer prognosis. Their expression in patients with systemic sclerosis (SSc) has not been widely elucidated. PIWI/piRNAs and their role in the pathogenesis of collagen accumulation in SSc was therefore investigated; no difference was found in the PIWIL1-4 levels between normal and cultured SSc dermal fibroblasts. Among piRNAs predicted to target SSc-related molecules, we first found significant piR-32364 up-regulation in SSc dermal fibroblasts, likely due to intrinsic TGF-βsignaling. Forced piR-32364 overexpression in normal fibroblasts significantly reduced COL1A1 expression both at mRNA and protein levels, but not COL1A2. Thus, piR-32364 overexpression in SSc fibroblasts may be the negative feedback against collagen up-regulation, which could suggest the potential of piRNAs as a therapeutic target.

Varicella zoster virus (VZV) causes chickenpox at the primary infection and then becomes latent in the spinal dorsal root ganglia; VZV can reactivate with aging, immunosuppression, stress, and other factors, occurring as herpes zoster (HZ) at 1–2 skin segments. HZ peripheral nerve complications caused by VZV reactivation include Hunt syndrome, segmental HZ paresis, post-herpetic neuralgia, and Guillain-Barré syndrome (GBS). We have encountered the rare HZ complications of upper-limb paresis, myeloradiculitis, and polyradiculoneuritis: an adult woman with upper-limb paresis consistent with the nerve root on segments above the thoracic HZ dermatome; another woman exhibiting ascending myeloradiculitis originating at the Th11–12 roots; an elderly woman with ascending VZV polyradiculoneuritis resembling GBS; an adult with VZV quadriplegia with disseminated HZ; and an elderly patient with VZV-associated polyradiculoneuritis. The three polyradiculoneuritis cases may be a new subtype of HZ peripheral neuropathy, but the pathophysiology for these HZ peripheral nerve complications unrelated to HZ dermatomes is unclear. We analyzed host factors, skin lesions, neurological and virological findings, and MRI results including 3D NerveVIEW in 15 Japanese patients treated at our facility for HZ peripheral neuropathy, including six differing from the HZ dermatome. Based on the clinical findings including MRI results of spinal ganglia and roots, we identified four possible routes for the patterns of VZV spread: (i) ascending spinal roots, (ii) ascending spinal cord, (iii) polyradiculopathy, and (iv) intrathecal spread. The incidence of HZ is increasing with the aging of many populations, and clinicians should be aware of these HZ neuropathies.

On September 18, 2023, the National Health Commission of China officially announced the "Second List of Rare Diseases". This list of 86 rare diseases, drafted in accordance with the "Working Procedures for Drafting the List of Rare Diseases", marks the second release of a rare disease list since the initial list was issued in May 2018. Following the release of the first batch, the Chinese Government introduced various policies to enhance the diagnosis and treatment of rare diseases, to promote the research on, development of, production of, and availability of rare disease medications in China, and to improve medication access for patients with rare diseases. Consequently, this has elevated the level of rare disease diagnosis and treatment, ensuring greater accessibility to treatment for affected individuals. The expansion of the rare disease list through the release of the "Second List of Rare Diseases" will further enhance rare disease management, increase awareness, improve diagnosis and treatment, facilitate the development and availability of more rare disease medications, establish a comprehensive support system for patients with rare diseases, and ultimately benefit a larger number of individuals affected by rare diseases. The definition of rare diseases in China should be refined by explicitly establishing corresponding criteria based on incidence, prevalence, or the number of affected individuals. Additionally, the mechanism for removal of diseases from rare disease lists should be enhanced, and prompt adjustments should be made regarding diseases that do not align with the selection principles of the list, taking into consideration environmental changes.

Dwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.

Rett syndrome (RTT) is a rare genetic neurological disorder that primarily affects girls and is caused by mainly mutations in the methyl-CpG-binding protein 2 (MECP2) gene, leading to critical issues in normal brain function. The condition has a global prevalence of 5 to 10 cases per 100,000 females, and there is currently no cure for RTT. However, therapy is available to manage the symptoms and improve quality of life. Trofinetide, an insulin-like growth factor 1, was originally developed as a stroke medication and progressed to Phase II clinical trials, where it exhibited favorable safety and efficacy profiles by improving several core RTT symptoms. Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder. It has also shown to be safe, well-tolerated and with no known drug interactions. These findings suggest that Trofinetide is a promising treatment option for individuals with RTT.

The current study examined sarcomatoid intrahepatic cholangiocarcinoma (S-iCCA). S-iCCA was a more aggressive subtype of intrahepatic cholangiocarcinoma (iCCA). Early detection and complete resection of tumors are very important. Reported here is a case of S-iCCA, and the diagnosis and treatment of S-iCCA are discussed. The patient underwent a tumor resection and was treated with chemotherapy and molecularly targeted drugs after surgery. The clinical pathologic features and treatment of S-iCCA are discussed based on the literature. An immunohistochemical examination revealed positivity for cytokeratin 7 (CK7), CK-pan, vimentin, and CK19 and negativity for hepatocyte paraffin 1 (HepPar-1) in sarcomatoid cells. This case suggests that the particular molecular characteristics of sarcomatoid cells have great clinical diagnostic value, and comprehensive treatment of S-iCCA based on surgery is described.