OBJECTIVE To systematically review the key regulatory requirements for pharmacy compounding drug products in the United States， and to provide references for improving the management framework of pharmacy compounding drug products in China， thereby ensuring the safety and accessibility of medication use. METHODS A literature revi ew was conducted to summarize the regulatory requirements and practical characteristics of pharmacy compounding drug products under Section 503A of the United States Federal Food， Drug， and Cosmetic Act . Based on regulatory experience of the United States， current status and existing deficiencies in pharmacy compounding drug products in China were analyzed， and targeted recommendations were proposed. RESULTS &CONCLUSIONS The United States has established a systematic regulatory framework for pharmacy compounding drug products under Section 503A， covering prescription management， active pharmaceutical ingredient management， list management of withdrawn or removed drugs and drugs that present demonstrable difficulties for compounding， recordkeeping management， interstate distribution and so on. Through standardized regulation of the entire compounding process and collaborative governance with expert advisory committees， this framework effectively balances individualized medication needs with drug quality and safety. In contrast， pharmacy compounding drug products in China remain largely confined to traditional Chinese medicine and face several challenges， including the lack of legal and regulatory support， inadequate quality control， lagging development of industry standards， and shortages of specialized personnel. It is recommended that China should establish a tiered regulatory system， develop comprehensive technical standards， build a localized regulatory framework， promote technological innovation， and strengthen professional talent cultivation to better balance the legitimate rights and interests of public medication use with drug safety and efficacy， thereby enhancing public health.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective: To construct microRNA(miR)-22 gene knockout(miR-22-/-) mice using CRISPR/Cas 9 technology, to breed miR-22-/- mice and to identify their genotypes. Methods : In this experiment, CRISPR/Cas 9 technology was used to construct miR-22-/- genetically engineered mice. After gene identification, the F0 generation miR-22-/- mice were mated with wild-type mice in the same litter to obtain F1 generation miR-22-/- mice. The miR-22 knockout efficiency was analyzed at the RNA level by real-time fluorescence quantitative polymerase chain reaction(qPCR). Western blot was used to detect the interaction between miR-22 and target genes. Results : miR-22-/- mice were successfully constructed using CRISPR/Cas 9 technology, gene identification was performed on the bred mice, and three stable genotypes of miR-22+/+,miR-22+/-, and miR-22-/- were identified. The real-time fluorescence quantitative PCR detection results confirmed that miR-22-/- mice showed almost no expression of miR-22 in the heart, liver, lung, kidney, spleen, and thymus tissues compared to wild-type mice in the same litter. Western blot analysis showed that the relative expression level of NLRP3 protein in miR-22-/- mouse tissues was lower than that in wild-type mice. Conclusion A miR-22-/- mouse model is successfully constructed, and stable genetic homozygous miR-22-/- mice is obtained. This indicates that miR-22 has an inhibitory effect on the downstream target gene NLRP3.

Objective To investigate the relationship between between the levels of serum malondialdehyde(MDA)and superoxide dismutase(SOD),the balance of oxidative/antioxidant stress,and the prognostic nu-tritional index(PNI)and the risk of early neurological deterioration in patients with acute ischemic stroke(AIS).Methods A total of 95 patients with suspected AIS admitted to the Second People's Hospital of Fos-han,Foshan from January to April 2023 were selected as the research subjects.Among them,71 patients who were finally diagnosed with AIS were included in the stroke group,and the remaining 24 non-AIS patients were included in the control group.According to the National Institutes of Health Stroke Rating Scale(NIH-SS)score,the stroke group was divided into the moderate-severe stroke group and the mild stroke group.Ac-cording to whether early neurological deterioration(END)occurred,it was divided into the END group and the non-END group.To analyze the correlations between the levels of serum SOD and MDA,SOD/MDA,and the PNI and the severity of stroke.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of each index for the risk of END.By fitting the indicators with high diagnostic efficacy,a Fisher discriminant function model for evaluating the risk of END was established to verify the overall accura-cy rate.Results The levels of serum MDA and SOD,SOD/MDA and the PNI in the moderate to severe stroke group were statistically different from those in the mild stroke group(P＜0.05).There were statistically sig-nificant differences in the levels of serum MDA and SOD,SOD/MDA and the PNI among the END group,the non-END group and the control group(P＜0.05).The areas under the curve(AUC)of SOD,MDA,SOD/MDA and PNI for evaluating END were 0.692,0.727,0.777 and 0.819,respectively.The Fisher discriminant function model established by fitting the NIHSS score,the SOD/MDA and the PNI has an overall accuracy rate of 85.9％.Conclusion The END risk prediction model established by applying the Fisher discriminant function can provide early and objective reference basis for clinical prediction of END risk and has certain practical value.

Objective:To explore the distribution characteristics of glioma-associated oncogene homolog 1 (Gli1) positive cells during orthodontic tooth movement process and conduct a proteomic analysis of these cells.Methods:Forty Gli1-LacZ transgenic mice were used to establish an in vivo orthodontic tooth movement (OTM) model for labeling Gli1 positive cells in Gli1-LacZ transgenic mice (OTM group) and an unforced control group, with tooth movement distance measured using micro-CT. The spatial relationship and distribution characteristics of Gli1 positive cells and H-type vessels of CD31 and endomucin (EMCN) in periodontal tissues were detected by immunofluorescence staining. Twenty Gli1-membrane-targeted tandem dimer Tomato (mT)/membrane-targeted green fluorescent protein (mG) double-genotype mice were bred and Gli1 positive cells were sorted for proteomic sequencing after tamoxifen induction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used for enrichment analysis. Results:The micro-CT three-dimensional reconstruction results showed that the mesial movement of the maxillary first molar in mice after 7 days of force application was (69±15) μm, indicating the successful establishment of the Gli1-LacZ transgenic mouse OTM model. Immunofluorescence staining showed that the blood vessels in periodontal tissue were mostly H-type vessels of CD31 and EMCN. The blood vessels in the periodontal tissues are predominantly H-type vessels positive for both CD31 and EMCN. The percentage of Gli1 positive cells in the OTM group, expressed as (54.5±13.2)%, and the relative fluorescence intensity, expressed as 2.6±0.9, were both significantly greater than those in the control group, which had a Gli1 positive cell percentage of (36.3±9.1)% ( t=3.60 , P=0.002) and a relative fluorescence intensity of 1.0±0.3 ( t=5.20, P<0.001). In contrast to the control group where only a small number of Gli1 positive cells were consistent with the distribution of H-type vessels, in the OTM group the number of Gli1 positive cells increased on the tension side were closely associated with the spatial distribution of H-type vessels. GO enrichment analysis of biological processes found that a large number of proteins in Gli1 positive cells were enriched in pathways such as angiogenesis and tissue remodeling. KEGG enrichment analysis found that related proteins were mainly enriched in pathways related to angiogenesis and Gli1, such as hypoxia-inducing factor 1 signaling pathway, vascular endothelial growth factor signaling pathway and hedgehog signaling pathway. Conclusions:The number of Gli1 positive cells increased on tension side and were closely related to H-type blood vessels in response to mechanical force during orthodontic tooth movement. This may be related to profile of inducing blood vessel formation and tissue remodeling.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective To investigate the clinical features of spinocerebellar ataxia 12(SCA12).Methods The clinical data of a family with SC A1 2 diagnosed by gene detection were retrospectively analyzed,and the literature was reviewed.Results Three patients in this family were diagnosed as SCA12.Among them,2 patients with clinical symptoms were＞45 years old,the clinical symptoms were head tremor,upper limb tremor,voice tremor,dystonia and ataxia.Another one case was 31 years old,did not have relevant clinical manifestations yet.Cranial MRI showed that cerebral cortex atrophy was more serious than cerebellar atrophy in 2 patients.Conclusion SCA12 typically presents with upper limb tremor,with head tremor being less common,as the disease progresses,symptoms such as ataxia,dystonia,Parkinsonism,and cognitive impairment may develop,due to its highly heterogeneous clinical features,genetic testing can be helpful for diagnosis.