BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective:To investigate the clinical application effects of the pedicled anterior intercostal artery perforator flap in breast reconstruction after breast-conserving surgery for breast cancer.Methods:This study was a retrospective observational study. From January to December 2023, 16 female breast cancer patients who met the inclusion criteria were hospitalized in the Department of Breast Surgery of the Affiliated Hospital of Southwest Medical University, with the age of (48±8) years. The pedicled anterior intercostal artery perforator flap was used for breast reconstruction of patients after breast-conserving surgery. After complete resection of tumor tissue, a "crescent-shaped" incision was designed at the inframammary fold. The pedicled anterior intercostal artery perforator flap was harvested based on the tumor location and the defect area after tumor removal. The flap was de-epithelialized, coapted, and rotated anterogradely or retrogradely to fill the defect. The donor site wound was closed with layered sutures. The following parameters were recorded: breast tissue loss volume during surgery, surgical duration, retention duration of the drainage tube, positive proportion of tumors in the breast incision margin tissue, breast loss ratio, flap survival, and incidence ratio of complications after operation. Patients were followed up for local recurrence or distant metastasis of tumor. At the last follow-up, the Ueda score was used to evaluate cosmetic outcomes of reconstructed breasts after breast-conserving surgery, and the Breast-Q scale version 2.0 was applied to assess patients' satisfaction and quality of life with breast reconstruction after breast-conserving surgery.Results:The breast tissue loss volume during surgery in this group of patients was 20-128 (59±34) cm3, the surgical duration was 105-200 (143±27) min, the retention duration of the drainage tube was 3-7 (4.6±1.0) d, and the positive proportion of tumors in the breast incision margin tissue was 1/16, with breast loss ratio of 0. After the surgery, the patient's transplanted flaps all survived. One patient had postoperative fat liquefaction in the surgical area, and the incidence ratio of postoperative complications was 1/16. The patients were followed up for 3-12 (11±4) months, and no local breast cancer recurrence or distant metastasis occurred. At the last follow-up, the cosmetic score of breast reconstruction after breast-conserving surgery were excellent in 6 cases, good in 8 cases, and fair in 2 cases, with an excellent and good ratio of 14/16. At the last follow-up, the highest score in the evaluation of patients' satisfaction with breast reconstruction and quality of life after breast-conserving surgery was the satisfaction with the surgeons, with a score of 59-100 (91±13), followed respectively by physiological health of the chest with a score of 60-100 (77±14), psychological health with a score of 35-100 (74±20), breast satisfaction with a score of 55-100 (73±13), satisfaction with information acquisition with a score of 53-100 (70±14), and sexual health with a score of 34-100 (70±23).Conclusions:The pedicled anterior intercostal artery perforator flap is safe and reliable for breast reconstruction after breast-conserving surgery for breast cancer, and can achieve high cosmetic effects and patient satisfaction. This flap is simple in design, easy to operate and highly reproducible, and is worthy of clinical promotion and application.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

Objective:To develop a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption (OIIRR) of maxillary incisors based on cone beam CT (CBCT) radiomics features and clinical characteristics of the orthodontic patients.Methods:Clinical and CBCT data from 101 orthodontic patients treated by the same attending orthodontist in the Department of Orthodontics, Stomatology Hospital of Tianjin Medical University from January 2019 to January 2024 were retrospectively collected. The sample included 42 class Ⅰ patients, 52 class Ⅱ patients and 7 class Ⅲ patients [age: (19.7±6.3) years], and a total of 394 maxillary incisors were analyzed. Potential influencing factors for moderate to severe OIIRR (root volume resorption rate≥10%) were collected from the patients′ CBCT and medical records, including initial age, gender, treatment duration, Angle′s classification, extraction or not, type of orthodontic appliance (fixed or clear aligner), changes in root inclination, root movement distance and direction, pre-treatment cephalometric measurements, pre-treatment root-bone relationship, pre-treatment root length, and pre-treatment radiomics features of the teeth. Univariate analysis was initially performed to screen for factors influencing moderate to severe OIIRR. Subsequently, least absolute shrinkage and selection operator (LASSO) regression, best subset regression, and random forest were used for feature selection to construct the OIIRR risk prediction model. The discrimination, calibration, and net benefit of the three risk prediction models were evaluated, and the optimal model was displayed using a nomogram.Results:LASSO regression identified clinical features including initial age (LASSO coefficient 0.052), treatment duration (LASSO coefficient 0.024), pre-treatment root length (LASSO coefficient -0.023), and vertical root movement distance (LASSO coefficient -0.029). Initial age and treatment duration were positively correlated with the severity of OIIRR, while root length and vertical root movement distance were negatively correlated. A total of 14 radiomics features were identified, including 2 original image features and 12 wavelet features. Best subset regression identified vertical root movement distance as the clinical feature and 7 radiomics features, including 1 original image feature and 6 wavelet features. The random forest model identified 8 wavelet features as important predictors, and all of which were radiomics features. Model performance evaluation showed that the random forest model had the highest discrimination, calibration, and net benefit, making it the optimal model, with radiomics features being the most important predictors.Conclusions:Based on the data from this study, radiomics features were identified as the most important predictors by the optimal model for OIIRR risk prediction. Predicting the occurrence of moderate to severe OIIRR before orthodontic treatment held potential clinical application value.

Objective:To validate the accuracy of three-dimensional anatomical models reconstructed from cone beam CT (CBCT) using micro-CT as the gold standard, and to evaluate the feasibility of performing anatomical analyses on such models.Methods:A total of 13 isolated deciduous teeth with intact roots were collected, including 5 anterior teeth and 8 molars, with a total of 34 root canals. The teeth were extracted from children aged 3-9 years who visited Peking University Hospital of Stomatology from January 2019 to April 2022 due to trauma or periapical disease, and were then scanned by micro-CT (with a voxel size of 0.018 mm) and CBCT (with a voxel size of 0.125 mm), respectively. Using a threshold-based semi-automated region segmentation method, anatomical models of these isolated teeth were reconstructed from the two CTs. Subsequently, the two CT reconstructed models were registered based on the iterative closest point algorithm, followed by deviation analysis. The key anatomical parameters were measured on the micro-CT and CBCT models, respectively, and the differences were calculated.Results:The CBCT reconstruction models were relatively accurate in the hard tissue morphology, and 97.1% (33/34) of the root canals were identified accurately. When it comes to the deviation analysis, the average distance between the matched points on the CBCT reconstruction models and the micro-CT models was (0.01±0.03) mm for the hard tissue, and (0.00±0.03) mm for the pulp chambers and canals, which did not affect clinical observation. The hard tissue and root canal length of CBCT models were both smaller than those of micro-CT models ( P<0.05), with a 95% limits of agreement of (-0.70, 0.14) mm for the hard tissue, and a 95% limits of agreement of (-1.93, 1.00) mm for the pulp chambers and canals. The impact of these differences on clinical operations was all within the acceptable range. Conclusions:Using micro-CT as a validate standard, CBCT with a voxel size of 0.125 mm was proved to be an effective tool for the reconstruction of deciduous teeth. Therefore, the reconstructed models were appropriate for studying deciduous teeth anatomy.