Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

The application of Mendelian randomization in ophthalmology research is increasing,and the idea of the in-strumental variable method effectively avoids the effects of confounding factors in observational research and randomized controlled trials.With convenient and cost-effective research methods,Mendelian randomization has inherent advantages in medical causal research.Primary open-angle glaucoma is a complex glaucoma disease related to genetics and other factors,but its diagnosis always delays.There is still a lack of powerful research inferring causal relationships currently.In this re-view,the progress of the application of Mendelian randomization in primary open-angle glaucoma was summarized,aiming to provide new insights into causal relationships of this disease.

Objective To study the clinical features and treatment outcomes of otitis media caused by antineu-trophil cytoplasmic antibody ANCA-associated vasculitis[otitis media with AAV(OMAAV)].Methods A total of 19 cases of OMAAV diagnosed between September 2015 to September 2022 were studied.OMAAV was defined using the criteria introduced by Japan Society of Otology.Results Median age of all patients was 61.8 years old,predominantly proteinase 3(PR3)positive(47.3％).Averaged score of vasculitis activity was 6.6.Disease also in-volved lung(84.2％),nose(73.7％)and facial nerve(21.0％).Pathological biopsy was performed in nine pa-tients,and two reports indicated ANCA-related disease.Fourteen affected ears of eight patients showed mixed hear-ing loss.The administration of corticosteroid together with an immunosuppressant significantly improved hearing,from averaged air conduction of 75.1±23.2 dB HL to 50.5±22.1 dB HL after treatment(P＜0.05).Conclusion Otologists shall be aware of OMAAV when handling intractable otitis media in elderly patients if bone conduction hearing gets worse and there are other affected organs.Immunological serum test is an important diagnostic basis.Most patients were misdiagnosed for certain time,and hearing level might not be improved unless early diagnose and proper treatment.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Objective To study the clinical features and treatment outcomes of otitis media caused by antineu-trophil cytoplasmic antibody ANCA-associated vasculitis[otitis media with AAV(OMAAV)].Methods A total of 19 cases of OMAAV diagnosed between September 2015 to September 2022 were studied.OMAAV was defined using the criteria introduced by Japan Society of Otology.Results Median age of all patients was 61.8 years old,predominantly proteinase 3(PR3)positive(47.3％).Averaged score of vasculitis activity was 6.6.Disease also in-volved lung(84.2％),nose(73.7％)and facial nerve(21.0％).Pathological biopsy was performed in nine pa-tients,and two reports indicated ANCA-related disease.Fourteen affected ears of eight patients showed mixed hear-ing loss.The administration of corticosteroid together with an immunosuppressant significantly improved hearing,from averaged air conduction of 75.1±23.2 dB HL to 50.5±22.1 dB HL after treatment(P＜0.05).Conclusion Otologists shall be aware of OMAAV when handling intractable otitis media in elderly patients if bone conduction hearing gets worse and there are other affected organs.Immunological serum test is an important diagnostic basis.Most patients were misdiagnosed for certain time,and hearing level might not be improved unless early diagnose and proper treatment.

The application of Mendelian randomization in ophthalmology research is increasing,and the idea of the in-strumental variable method effectively avoids the effects of confounding factors in observational research and randomized controlled trials.With convenient and cost-effective research methods,Mendelian randomization has inherent advantages in medical causal research.Primary open-angle glaucoma is a complex glaucoma disease related to genetics and other factors,but its diagnosis always delays.There is still a lack of powerful research inferring causal relationships currently.In this re-view,the progress of the application of Mendelian randomization in primary open-angle glaucoma was summarized,aiming to provide new insights into causal relationships of this disease.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.