Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review.

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.

Role of IFITM2 in osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.

Interferon-inducible transmembrane (IFITM) are a family of small proteins localized to plasma and endolysosomal membranes. Their functions beyond restricting viral entry and replication have been revealed in recent years. IFITM5 is involved in bone mineralization and is an osteogenic cell surface marker. IFITM1 and 3 interact with desmin and myosin, and are involved in myogenic differentiation. This study found upregulation of Ifitm2 during osteogenic differentiation of C3H10T1/2 cells. This positively correlated to the expression of osteogenic differentiation markers Col1a1, Alp, Runx2, and Ocn. Knockdown of Ifitm2 by siRNAs inhibited osteogenic differentiation, calcium deposition, and osteogenic marker expression of C3H10T1/2 cells. The osteoblast transcriptome revealed that knocking down Ifitm2 affected the expression Wnt signaling pathway-related genes, including Wnt family members, their receptors Lrp, Frizzled, and Lgr, and transmembrane molecule Rnf43 that suppresses the Wnt signaling pathway. Luciferase assays indicated enhancement of canonical Wnt signaling pathways by Ifitm2 overexpression. Furthermore, IFITM2 was colocalized in the metaphyseal bone and growth plate of the mouse tibial bone with SP7, a transcription factor essential for osteoblast differentiation and bone formation. These findings reveal a possible novel function and potential mechanisms of Ifitm2 in osteogenic differentiation.

Identification of novel and de novo GABRB1 mutation in Chinese patient with developmental and epileptic encephalopathy 45.

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 ß1-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.

Circ_KIAA0922 regulates Saos-2 cell proliferation and osteogenic differentiation by regulating the miR-148a-3p/SMAD5 axis and activating the TGF-ß signaling pathway.

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.

Analysis of marketed orphan drugs in China.

In recent years, China has increased attention on the issue of rare diseases, and the government has promulgated rare disease-related policies to gradually improve rare disease diagnosis, treatment, drug marketing, and patient burden. Orphan drugs were added to the medical insurance directory in 7 batches, of which 22 drugs were first included in the 2004 medical insurance directory and 8, 16, 12, 7, 8, and 7 were included in the 2009, 2017, 2019, 2020, 2021, and 2022 versions, respectively. Currently, 106 orphan drugs are marketed in China, which are suitable for treating 53 rare diseases such as hematologic diseases, congenital metabolism disorders, neuropathies, and digestive system diseases and for other treatment fields. The drugs are mainly manufactured in 15 countries such as China, Switzerland, and the USA, of which 10 drugs can be used to treat different rare diseases. At the same time, there are multiple treatments available for 25 rare diseases. In this paper, we examined the manufacturers, marketing status, indications, and inclusion of orphan drugs in the National Basic Medical Insurance Directory to describe and analyze the current status of 106 orphan drugs that are currently marketed in China to provide a reference for rare disease policy formulation and drug development.

The novel role of IFITM1-3 in myogenic differentiation of C2C12 cells.

Interferon-induced transmembrane proteins (IFITMs 1, 2, and 3) play a critical role in preventing pathogen infection in vertebrates. They are also involved in the occurrence and prognosis of cancer. Myogenesis is a complex process regulated by several factors. This study disclosed that Ifitm1-3 were upregulated in the process of myogenic differentiation of C2C12 myoblasts on days 3, 5, and 7. This positively correlated with the expression of differentiation factors MyoD, myogenin, Mrf5, and desmin. Furthermore, knockdown of Ifitm1-3 by their individual siRNAs inhibited myogenesis of C2C12 myoblasts, with relative downregulation of MyoD, myogenin, Mrf5, and desmin. Subsequently, myotube formation and fusion percentage decreased. Co-immunoprecipitation combined with LC-MS/MS analysis uncovered the interaction proteins of IFITM1 and IFITM3 in C2C12 myoblasts. A total of 84 overlapped interaction proteins of IFITM1 and IFITM3 were identified, and one of the clusters was engaged in cytoskeletal and sarcomere proteins, including desmin, myosin, actin, vimentin, nestin, ankycorbin, and nucleolin. Hence, we hypothesize that these interacting proteins may function as scaffolds for IFITM1-3, possibly through the interaction protein desmin to initiate further interaction with other proteins to participate in myogenesis; however, the molecular mechanisms remain unclear. Our study may contribute to the development of novel therapeutics for myopathic diseases.

Treatment effects after maxillary expansion using invisalign first system vs. acrylic splint expander in mixed dentition: a prospective cohort study.

BACKGROUND: Invisalign First System (First) is a new type of orthodontic appliance for maxillary arch expansion in mixed dentition children. Till now, few studies have evaluated the expansion effects of First versus other appliances. What's more, most studies of arch expansion did not include a natural group to rule out growth effects. This prospective cohort study aimed to evaluate the dental and dentoalveolar effects using First or acrylic splint rapid maxillary expander (RME) in adolescents excluding growth factors. MATERIALS AND METHODS: After screening by strict inclusion criteria and propensity score matching (PSM), fifty-one patients were included: First group (n = 17), RME group (n = 17), and natural growth (NG) group (n = 17). Nine indicators including dental arch width, dentoalveolar arch width, and inclination of the molars were measured on digital dental casts at baseline (T0) and six-month follow-up (T1). Paired t-tests were used for intra-group results, and two-sample independent t-tests were used for inter-group comparisons. RESULTS: There was no significant increase in all indicators within six months in the NG group (p > 0.05). In the First group and RME group, all width indicators were significantly increased after treatment (p < 0.05). The RME group exhibited greater expansion than the First group in intercanine width, first interpremolar width, second interdeciduous molar width, first intermolar width, arch perimeter, intercanine dentoalveolar width, intermolar dentoalveolar width, and inclination of the molars (p < 0.05). Whereas, there was no significant difference in arch depth between the two treated groups. CONCLUSIONS: Both First and RME can expand the maxillary arch in mixed dentition. In case of mild to moderate maxillary transverse deficiency (MTD), Invisalign First System could be a reasonable option. RME shows significant better efficiency of dental arch expansion than First, recommended for patients with severe MTD. TRIAL REGISTRATION: This prospective study was registered on ClinicalTrials.gov (01/02/2022, registration number: ChiCTR2200056220). The trial was approved by the Ethical Committee of the Hunan Xiangya Stomatological Hospital Central South University (20,200,088), and informed consent was obtained from all subjects and their legal guardian(s).

Obstructive sleep apnea: a follow-up program in its relation to temporomandibular joint disorder, sleep bruxism and orofacial pain.

OBJECTIVE: To evaluate the correlation between obstructive sleep apnea (OSA) and temporomandibular joint (TMJ) morphology, tooth wear condition, orofacial pain through a follow-up program. MATERIALS AND METHODS: Seventy one OSA patients were divided into three groups according to their (apnea hypopnea index) AHI: mild group (n = 23), moderate group (n = 24), and severe group (n = 24). All patients had OSA therapies around six months after confirm the diagnosis of OSA. The tooth wear score and orofacial pain condition of all patients were recorded via clinical examination. Cone beam computed tomography (CBCT) images were also taken when confirm the diagnosis of OSA (T0), 6 months after the diagnosis (T1), and 6 months after the OSA treatment (T2). Parameters indicating the condylar morphology and joint space were evaluated. The differences of clinical symptoms and TMJ conditions among T0, T1 and T2 time point were detected in the three groups respectively. The changes in T1-T0 and T2-T1 of all descriptions among three groups were also compared. The correlations between AHI and clinical symptoms were detected with Spearman correlation analysis. RESULTS: In mild group, there was no difference in all clinical symptoms and TMJ morphology among the three time points. Both in moderate and severe group, the condylar volume, superficial area, wear score, visual analogue scales (VAS), and R value (indicating condyle position) displayed significant differences among the three time points (P < 0.05). From T0 to T1, mild group displayed fewer decreases in the condylar volume and superficial area and fewer increases in wear score than that in moderate and severe group (P < 0.05). From T1 to T2, there was a greatest reduction in severe group for R value, and significant difference in the description of VAS and R value were found among the three groups. AHI was negatively correlated condylar volume and condylar superficial area, and was positively correlated with tooth wear score and VAS (P < 0.05). CONCLUSION: Moderate to severe OSA will aggravate orofacial pain and tooth wear, affect TMJ volume and superficial area, even change the location of condyles. Appropriate OSA therapies may be effective ways to alleviate these adverse effects in long-term.

Treatment effects after maxillary expansion using tooth-borne vs tissue-borne miniscrew-assisted rapid palatal expansion appliance.

INTRODUCTION: The study investigated the skeletal effects and root resorption in young adults with maxillary transverse deficiency after tissue-borne or tooth-borne mini-implant anchorage maxillary expansion. METHODS: Ninety-one young adults with maxillary transverse deficiency, aged 16-25 years, were divided into 3 groups according to the treatment method: group A (n = 29) comprising patients treated with tissue-borne miniscrew-assisted rapid palatal expansion (MARPE), the group B (n = 32) comprising patients treated with tooth-borne MARPE, and the control group (n = 30) comprising patients only treated with fixed orthodontic therapies. Pretreatment and posttreatment cone-beam computed tomography images were used to assess the change of maxillary width, nasal width, first molar torque and root volume by paired t test in the 3 groups, respectively. Analysis of variance and Tukey least significant difference analysis were used to detect the changes of all descriptions among the 3 groups P <0.05. RESULTS: In the 2 experimental groups, we observed significant increases in the width of the maxilla, nasal, and arch width, as well as the molar torque. In addition, the height of the alveolar bone and the root volume decreased significantly. There were no significant differences in the maxilla, nasal, and arch width change between the 2 groups. Group B displayed more increases in buccal tipping, alveolar bone loss, and root volume loss than group A (P <0.05). Compared with groups A and B, the control group showed negligible tooth volume loss, with no expansion effect in both skeletal and dental descriptions. CONCLUSIONS: Tissue-borne MARPE produced the same expansion efficiency as tooth-borne MARPE. However, tooth-borne MARPE causes more dentoalveolar side effects in buccal tipping, root resorption and alveolar bone loss.

Morphological changes in alveolar bone thickness and height after orthodontic proclination or labial movement combined with autogenous soft tissue grafting: a CBCT evaluation.

BACKGROUND: Autogenous soft tissue grafting is indicated in thin gingival biotypes before orthodontic proclination or labial movements to increase the keratinized gingiva and prevent gingival recession. However, its effect on local alveolar bone remodeling is unclear. The aim of this study was to investigate the effects of autogenous soft tissue grafting on local alveolar bone after orthodontic proclination or labial movements. METHODS: Sixteen patients with a thin scalloped gingival biotype, narrow keratinized gingiva, or thin cortical bone requiring orthodontic proclination or labial movement of teeth were included. Cone-beam computed tomography (CBCT) images were obtained before grafting and at least 6 months after surgery. Sixty mandibular teeth were included, and the vertical bone level and horizontal labial bone thickness were measured. The results were compared using paired t-tests or Wilcoxon signed-rank test. RESULTS: The horizontal labial bone thickness increased, especially at 6 mm below the cementoenamel junction (CEJ) in the mandibular central and lateral incisors (P < 0.05). The total alveolar bone area of the canines, first premolars, and second premolars increased at 3, 6, and 9 mm below the CEJ, respectively, and the differences were statistically significant (P < 0.05). Additionally, vertical bone height increased minimally on the labial side, but the differences were not statistically significant (P > 0.05). CONCLUSIONS: New bone regeneration was observed on the labial (pressure) side after autogenous soft tissue grafting, which may represent a mechanism to effectively prevent gingival recession and maintain periodontal health. IRB APPROVAL: All the experimental procedures involving humans in this study were approved by the Medical Ethics Committee of Xiangya Stomatological Hospital, Central South University ( No. 20190048).

Factors related to microimplant-assisted rapid palatal expansion in teenagers and young adults: A cone-beam computed tomography study.

INTRODUCTION: For patients with maxillary transverse deficiency, selecting an appropriate therapeutic method is important for the treatment effect and prognosis. Our study aimed to explore factors related to microimplant-assisted rapid palatal expansion (MARPE) in teenagers and young adults using cone-beam computed tomography. METHODS: Twenty-five patients who underwent MARPE were included in this retrospective study from February 2014 to June 2019. Midpalatal suture density (MPSD) ratio, midpalatal suture maturation (MPSM), bone effect, dentoalveolar effect, and dental effect in maxillary first molar were evaluated using cone-beam computed tomography. Spearman correlation analysis was used to analyze the correlation between the MPSD ratio, MPSM, age, and the expansion amount generated by MARPE. RESULTS: Twenty-five patients (mean age, 19.84 ± 3.96 years; range, 15-29 years) with maxillary transverse deficiency were analyzed. Age was negatively correlated with bone expansion, alveolar expansion, and alveolar change (all P <0.05). There was a negative correlation between MPSM and nasal cavity variation, bone expansion, and alveolar change (all P <0.05). The bone expansion was negatively correlated with MPSD ratio 3 (r = -0.417; P <0.05) and MPSD ratio 4 (all P <0.05). CONCLUSIONS: Age, MPSM, and MPSD ratio were significantly related to the MARPE effect. Age, MPSM, and MPSD ratio should be considered when choosing MARPE.

The role of rapid maxillary expansion in pediatric obstructive sleep apnea: Efficacy, mechanism and multidisciplinary collaboration.

This review aims to provide current knowledge about the efficacy, mechanism, and multidisciplinary collaboration of rapid maxillary expansion (RME) treatment in pediatric obstructive sleep apnea (OSA). OSA is a chronic disease characterized by progressively increasing upper airway resistance, with various symptoms and signs. Increasingly the evidence indicates that RME is a non-invasive and effective therapy option for children with OSA. Besides, the therapeutic mechanism of RME includes increasing upper airway volume, reducing nasal resistance, and changing tongue posture. Recent clinical researches and case reports also show that a multidisciplinary approach improves sleep-disordered breathing in children. Applied with adenotonsillectomy, mandibular advancement, continuous positive airway pressure, and comprehensive orthodontic treatment, RME can be more effective in recurrent or residual OSA.

Efficient biodegradation of tris-(2-chloroisopropyl) phosphate by a novel strain Amycolatopsis sp. FT-1: Process optimization, mechanism studies and toxicity changes.

In this study, a newly isolated strain Amycolatopsis sp. FT-1 was confirmed to be an efficient tris-(2-chloroisopropyl) phosphate (TCPP) degrader. The maximum degradation efficiency of 100 % was achieved when glucose concentration was 6.0 g/L, TCPP concentration was 1.1 mg/L, pH was 6.3 and temperature was 35 °C. Proteome analysis indicated that TCPP was transformed into diester, monoester and ketone product through hydrolysis by phosphoesterase and oxidation mediated by proteins involved in bio-Fenton reaction. The increased expression of proteins serving as organic hydroperoxides scavenger and two subunits of xanthine dehydrogenase enabled Amycolatopsis sp. FT-1 to defend against TCPP-induced oxidative damage. Meanwhile, proteins involved in the resistance to proteotoxic stress were found to be up-regulated, including Hsp70 protein, ATP-dependent Clp protease proteolytic subunit, elongation factor G and trehalose synthesis-related enzymes. The overexpression of TetR/AcrR family transcriptional regulator and multidrug efflux transporter also benefited the survival of Amycolatopsis sp. FT-1 under TCPP stress. Luminescent bacteria test showed that biotoxicity of TCPP was remarkably decreased after biodegradation by Amycolatopsis sp. FT-1. To the best of our knowledge, this is the first study to report the biotransformation of TCPP by pure strain and to offer important insights into the proteomic mechanisms of TCPP microbial degradation.

Effects of occlusal splint and exercise therapy, respectively, for the painful temporomandibular disorder in patients seeking for orthodontic treatment: a retrospective study.

OBJECTIVE: To evaluate the effect of hard stabilization splints (HSS), counselling and exercise therapies, respectively, for the painful temporomandibular disorder (TMD) in patients seeking for orthodontic treatment through magnetic resonance imaging (MRI) and clinical examination. MATERIALS AND METHODS: Eighty-seven TMD patients were divided into two groups according to their therapies: the HSS group (n = 43) comprising of patients treated with HSS, counselling and masticatory muscle exercises; the control group (n = 44) comprising of patients treated with counselling and masticatory muscle exercises alone. All patients had orthodontic therapies after the first treatment phase. The joint pain and clicking of all patients were recorded via clinical examination. MRIs of HSS groups were taken before (T0), after the first phase (T1), and after the orthodontic treatment (T2). Parameters indicating the condyles and articular discs were evaluated. Clinical symptom (pain and clicking) changes among T0, T1 and T2 time point were detected in the two groups respectively. The significant differences between HSS and control groups, as well as between male and female were tested at T1 and T2. Position changes of condyles and discs in HSS group among T0, T1 and T2 were detected in male and female respectively. RESULTS: After the first treatment phase, there was no difference in the decrease of facial pain between the two group, as well as between male and female in the two groups (P > 0.05). Clicking decreasing was not statistically significant. After the whole orthodontic periods, the TMJ pain relapsed in female of the control group, and the number of female's pain joints was more than male's (P < 0.05). In the HSS group, the posterosuperior movements of discs and the anteroposterior movements of condyles were recorded in closing position (P < 0.05). After the whole orthodontic periods, female's disc-condyle angles increased, the discs to HRP distance decreased and condyles to VRP distance increased when compared with the data of T1 (P < 0.05). CONCLUSIONS: For the orthodontic patients with painful TMD, HSS combined with counselling and exercise therapies before orthodontic treatment could provide pain relief. HSS is helpful to improve the position and relation of discs and condyles. In addition, male's prognosis is better than female's in terms of stability.

Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke.

Background: Polymorphisms of the apolipoprotein E (APOE) gene are related to the efficacy of statin therapy. The biological functions of the APOE subtypes determine the metabolism of blood plasma lipids and the progression of atherosclerosis. This study aimed to explore the impact of APOE gene polymorphisms on the effect of atorvastatin on lipid regulation and plaque stabilization. Methods: The study was a prospective cohort study that consecutively included patients with acute ischemic stroke (AIS) in the Department of Neurology, Shanghai Tenth People's Hospital, from December 2018 to December 2019. The patients were divided into E2, E3, and E4 groups according to their APOE genotype. Atorvastatin (20 mg) was administrated to all patients. Changes in blood lipid levels over 3 months and plaque size and stability over 12 months were analyzed. Results: We enrolled 253 consecutive patients with AIS, of whom, 136 had carotid atherosclerotic plaques. Two patients with genotype E2/E4 were excluded. There were 30 patients in the E2 group (12.0%), 191 patients in the E3 group (76.0%), and 30 patients in the E4 group (12.0%). The lowest percentage reduction in low-density lipoprotein cholesterol (LDL-C) was observed in the E4 group (41.2%), while the highest percentage reduction was observed in the E2 group (17.6%). The plaques in the E2 group showed slower progression, while those in the E4 group showed more rapid progression. Conclusion: APOE gene polymorphisms affect the biological functions of atorvastatin. Compared to the ε3 or ε4 allele, the ε2 allele exerted a greater lipid-lowering effect on LDL-C levels, enhanced the ability of atorvastatin to stabilize carotid artery plaques, and slowed carotid artery plaque progression.

Incidence and prevalence of 121 rare diseases in China: Current status and challenges: 2022 revision.

The current study updated data on the incidence and prevalence of 121 rare diseases listed in China's First List of Rare Diseases to provide rationales and references for the development and promotion of rare-disease-related policies. The National Health Commission of the People's Republic of China issued the Rare Disease Diagnosis and Treatment Guide (2019) (denoted here as China's Rare Disease Diagnosis and Treatment Guide). Then 121 diseases were registered with the national rare disease diagnosis and treatment network. The incidence/prevalence of 121 rare diseases varied from country to country. Data are available for a total of 76 rare diseases (76 of 121 rare diseases, 62.81%) in China, including data on the incidence of 23 rare diseases (19.01%) and data on the prevalence of 66 (54.55%). There are data on the incidence/prevalence of 112 rare diseases (112 of 121 rare diseases, 92.56%) at the global level, including data on the incidence of 86 rare diseases (71.07%) and data on the prevalence of 91 (75.21%). On average, the incidence of progressive muscular dystrophies, hyperphenylalaninemia, citrullinemia, and methylmalonic acidemia is over 1/10,000 in China. The prevalence of coronary artery ectasia, congenital scoliosis, retinitis pigmentosa, severe congenital neutropenia, congenital hyperinsulinemic hypoglycemia, and osteogenesis imperfecta is over 1/10,000 in China. All of these figures are beyond the cut-off of 1/10,000 according to the 2021 definition of rare diseases in China. As registration and investigation of rare diseases continues, the spectrum of rare diseases in some provinces is expanding. Diseases such as idiopathic pulmonary arterial hypertension, hepatolenticular degeneration, hemophilia, amyotrophic lateral sclerosis, idiopathic pulmonary fibrosis, and multiple sclerosis are relatively prevalent in some regions and cities of China. Registration efforts promote the correction of incidence/prevalence data, development of orphan drugs, coverage by medical insurance, and development of clinical and diagnostic pathways.

Comprehensive bioinformatics analysis of susceptibility genes for developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a multifactorial disease, which occurs under environmental and genetic influence. The etiopathogenesis of DDH has not been fully explained. As research progresses, many candidate genes have been found to be closely related to the occurrence of DDH. In this study, we comprehensively examined 16 susceptibility genes of DDH using bioinformatics. COL1A1 encodes the pro-alpha1 chains of type I collagen, which is the major protein component of the bone extracellular matrix (ECM). The genes displaying the most statistically significant co-expression link to COL1A1 are ASPN, TGFB1, DKK1, IL-6, TENM3 and GDF5. DKK1, FRZB and WISP3 are components of the Wnt signaling pathway. CX3CR1 and GDF5 regulate chondrogenesis through the canonical Wnt signaling pathway. ASPN could induce collagen mineralization through binding with collagen and calcium. Integrated bioinformatics analysis indicates that ECM, Wnt signaling pathway and TGF-ß signaling pathway are involved in the occurrence of DDH. These provide a basis for further exploring the pathogenesis of DDH.

The Joint Effects of Social Norm Appeals and Fear Appeals in COVID-19 Vaccine Campaign Posters on Self-Perceived Communication Quality and Vaccination Intention.

To understand how different types of cues in vaccine education messages affect attitude toward campaign messages and vaccination intention, this study examined the impact of the presence of social norm appeals (individual vs. group cues) and the presence of fear appeals in coronavirus disease 2019 (COVID-19) vaccine campaign posters on perceived communication quality and vaccination intention. A 2 (social norm appeal: individual cue vs. group cue) × 2 (fear appeal: absence vs. presence) × 3 (repetition) within-subject factorial design experiment was conducted in China. Findings demonstrated that the presence of fear appeals in COVID-19 vaccine campaign posters elicited lower levels of perceived communication quality and vaccination intention than those without fear appeals. The interactive effect of fear appeals and social norm appeals was also found to be significant. Specifically, positive-framed messages (i.e., absence of fear appeals) with group cues and fear appeal messages with individual cues elicited higher perceived information quality and stronger vaccination intention than other types of messages. Understanding how these cues function jointly in COVID-19 vaccine campaign messages will help public health practitioners create more effective intervention strategies.

Pan-cancer analysis of osteogenesis imperfecta causing gene SERPINF1.

Osteogenesis imperfecta (OI) type VI causative gene SERPINF1, encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein (pigment epithelium-derived factor, PEDF) has anti-tumor, anti-angiogenesis, anti-inflammation, nutrition and nerve protection functions, and participates in fat metabolism. In this paper, a series of bioinformatics analyses were conducted based on the regulation of SERPINF1 in the human. Pan-cancer analysis of SERPINF1 revealed it to play a role in the prognosis of tumors, especially in KIRC, and that high expression of SERPINF1 leads to a poor prognosis of the disease, the occurrence of which is largely related to the high expression of SERPINF1 leading to immune infiltration of cancer associated fibroblasts. Mutation analysis found that SERPINF1 had eight identical amino acids alterations sites with different in both cancer and OI patients. which hints the possible relationship between genotype and phenotype.