Primary pigment dispersion syndrome(PDS)is characterized by pigment granules released from the pigment epithelium of iris, and their deposition in anterior segment of eye, particularly in the trabecular meshwork(TM). This condition may lead to elevated intraocular pressure(IOP),which further causes optic nerve damage, and progresses to pigmentary glaucoma(PG). PDS predominantly affects young myopic individuals and shows heterogeneous clinical manifestations. It may occur sporadically or in familial inheritance. It has been reported that the pathogenic genes include those involved in melanogenesis and melanosome homeostasis(e.g., PMEL, MC1R, SLC45A2, and TYR), and genes related to ocular development and anterior segment formation(e.g., CPAMD8, GSAP, and GRM5).The pathogenesis of PDS is closely associated with posterior iris concavity and reverse pupillary block, which may change the dynamics of aqueous humor, along with persistent liberation of pigmented granules by friction of iris and zonules. Pigmented granules accumulating in the TM may cause mechanical obstruction of TM, and increase the phagocytic burden of the cells, and result in cellular dysfunction and structural damage of TM. All these changes contribute to sustained elevation of IOP and optic neuropathy. Primary management of PDS involves regular follow-up and assessment of the risk of IOP elevation. Laser peripheral iridotomy may be considered to reduce posterior iris concavity in PDS. Treatment of PG focuses on IOP control for long term, which include topical medications, laser trabeculoplasty, and filtering or drainage surgery. Development of experimental animal models harboring human pathogenic genes and exhibiting PDS phenotypes is needed to facilitate in-depth research into the pathogenesis of PDS.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

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*

Background Diesel engines are widely used in transportation, agriculture, construction, industry, and other fields. Diesel exhaust, classified as a Group 1 carcinogen, emits particles (DEP) that can penetrate deep into the respiratory tract, posing significant health risks. DEP pollution is particularly severe in confined environments, necessitating effective control measures. Objective Under laboratory simulation conditions, to explore the spatiotemporal distribution characteristics of the mass and number concentrations of DEP as it diffuses indoors and to reveal the effects of ventilation and additional airflow on indoor DEP pollution levels. Methods A diesel engine was placed in a laboratory (length 3.39 m × width 2.85 m × height 2.4 m) with its exhaust emitted from east to west. An air purifier was installed 1 m south of the engine. Eight measurement points (1 m horizontal distance from the exhaust outlet, height: 1 m/1.5 m) were setup to monitor DEP concentrations using portable laser particle sizers. The effects of engine power (4.05 kW vs. 5.15 kW), ventilation (maximum airflow: 600 m³·h⁻¹), additional airflow intensity (low and high), and direction (forward/reverse) on DEP pollution were analyzed. DEP levels of 5 diesel vehicle models were also compared. Results The mass and number concentrations of DEP indoors increased immediately after the diesel engine started. The peak mass concentration time at the eastern measurement point (−1, 0) m opposite to the exhaust direction (17.70 min) was significantly longer than that at the western (1, 0) m (16.20 min), southern (0, -1) m (14.45 min), and northern (0, 1) m (12.70 min) points (P<0.05), with no significant differences between the other points (western, southern, and northern) (P>0.05). The northern point (0, 1) m exhibited the highest DEP mass and number concentration peaks (174.62 μg·m⁻³, 1319.85 p·cm⁻³), significantly exceeding those at the southern (0, −1) m (129.89 μg·m⁻³, 1175.24 p·cm⁻³), eastern (−1, 0) m (140.12 μg·m⁻³, 1120.53 p·cm⁻³), and western (1, 0) m (147.60 μg·m⁻³, 818.62 p·cm⁻³) points (P<0.05), and no significant differences were observed among other points (P>0.05). There were no significant differences in peak DEP mass and number concentrations by measurement heights (P>0.05). Diesel engine power, ventilation, airflow intensity, and airflow direction had no significant effect on the time of peak DEP concentration (P>0.05). However, higher engine power (5.15 kW) produced greater DEP peaks [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] than the 4.05 kW engine power [(168.41±12.65) μg·m⁻³, (1284.45±71.30) p·cm⁻³] (P<0.05). The peak mass concentration [(342.04±35.03) μg·m⁻³] and number concentration [(1886.87±57.91) p·cm⁻³] of DEP in the non-ventilated group were significantly higher than those in the ventilated group [(186.66±19.29) μg·m⁻³, (1382.79±122.56) p·cm⁻³] (P<0.001). Forward airflow elevated DEP mass concentrations compared to reverse airflow (287.71 μg·m⁻³ vs. 243.74 μg·m⁻³, t=−2.592, P=0.009), but no effects on DEP number concentration (P>0.05). Significant differences in mass concentration were observed among selected 5 vehicle models (Z=38.109, P<0.001). Conclusion The operation of diesel engines will emit a large amount of particulate matter, causing pollution in enclosed spaces. Diesel engines with greater power have higher levels of DEP pollution emissions. Based on the spatiotemporal distribution characteristics, it is recommended to set the operation position in the reverse direction of exhaust emissions and close to air purifiers, while avoiding the use of additional air flow equipment.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

OBJECTIVE: Investigating the clinical efficacy of treating dorsally displaced distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires. METHODS: Retrospectively analyzed the clinical data of 15 patients with distal radial double-column Die-punch fractures treated with an external fixator combined with Kirschner wire between July 2020 and January 2023. There were 10 males and 5 females;6 cases on the left side and 9 on the right;age ranged from 22 to 76 years old. Recorded the preoperative and the final follow-up Cooney wrist function scores for the patients. The fracture healing time, and occurrence of complications were recorded. RESULTS: All 15 patients were followed up ranged from 12 to 16 months post-operation. All fractures achieved bony union, healing time ranging form 8 to 16 weeks. Not a single patient exhibited complications such as surgical site infection, fracture redislocation, or tendon injury. All individuals had their Kirschner wires and external fixation devices removed six weeks post-operatively and commenced rehabilitative therapy for wrist articulation. The Cooney wrist function scores at preoperative and ranged from 5 to 45 scores, at the latest follow-up ranged from 65 to 100 scores. At the final follow-up, the results were assessed as excellent in 10 patients, good in 4 patients, and fair in 1 patient. CONCLUSION The clinical efficacy of treating distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires is satisfactory.
Humans ; Male ; Female ; Middle Aged ; Adult ; External Fixators ; Bone Wires ; Aged ; Retrospective Studies ; Radius Fractures/physiopathology* ; Young Adult ; Fracture Fixation/methods*

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires