ObjectiveTo investigate the mechanism of Zuogui Wan （ZGW） in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells （OSCs） for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group， a model group， a low-dose ZGW group （2.7 g·kg^-1）， a high-dose ZGW group （5.4 g·kg^-1）， and an estradiol valerate group （0.15 mg·kg^-1）， with 8 mice in each group. Except the blank group， all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg^-1 to establish an ovarian aging mouse model. After successful modeling， each group was continuously administered for 4 weeks， once daily. The physiological status of the mice was observed， and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin （HE） staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and mouse interleukin-6 （IL-6） levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS， STING， p-STING， TANK-binding kinase 1 （TBK1）， p-TBK1， interferon-induced transmembrane protein 3 （Fragilis）， and Vasa homolog protein （MVH）. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues， and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 （Oct4） were calculated. ResultsCompared with the blank group， the model group showed reduced body weight， ovarian wet weight， and ovarian index （P<0.01） and a disordered estrus cycle （P<0.01）. In addition， the levels of serum follicle-stimulating hormone （FSH）， TNF-α， IL-6， and IL-1β were increased （P<0.01）， while anti-Müllerian hormone （AMH） and estradiol （E₂） levels were decreased （P<0.01）. The protein expression of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue was increased （P<0.05， P<0.01）， while that of OSCs stemness factors MVH and Fragilis was reduced （P<0.01）. Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs （P<0.01）. The mRNA expression of inflammatory factors TNF-α， IL-6， and IL-1β in ovarian tissue was increased （P<0.05， P<0.01）. Compared with the model group， the treatment groups exhibited improved body weight， ovarian wet weight， and ovarian index （P<0.05） and a reduced rate of estrus cycle disorder （P<0.05， P<0.01）. The levels of serum FSH， TNF-α， IL-6， and IL-1β were decreased （P<0.05， P<0.01）， while AMH and E₂ levels were increased （P<0.01）. The protein expression levels of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue were decreased （P<0.05）， while the protein expression of MVH and Fragilis was increased （P<0.05）， and the fluorescence intensities of MVH and Oct4 were increased （P<0.05， P<0.01）. The mRNA expression of inflammatory factors in ovarian tissue was decreased （P<0.05）. ConclusionZGW alleviate ovarian inflammatory response， regulate ovarian microenvironment homeostasis， and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway， thereby improving ovarian function and delaying ovarian aging.

BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)％and(6.65±0.08)％,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.

Objective: To investigate the regulatory relationship between long non-coding RNA LINC01578 and c-Myc, and to explore the effect of LINC01578 on the metabolic process of oral squamous cell carcinoma(OSCC). Methods: After c-Myc was knocked down in OSCC cell line CAL27, LINC01578, a long non-coding RNA that is positively regulated by c-Myc, was identified by high-throughput sequencing technology. qRT-PCR was employed to measure the expression levels of c-Myc and LINC01578 in OSCC tissues and adjacent normal tissues. Following overexpression or knockdown of c-Myc in CAL27 and HN6 cells, qRT-PCR was conducted to validate the consistency with sequencing results. The binding of c-Myc to the LINC01578 promoter was confirmed using a dual luciferase reporter assay. Seahorse, ATP production and lactate production assays were utilized to examine the impact of c-Myc on glucose metabolism in OSCC via LINC01578. Colony formation assays assessed the proliferative capacity of OSCC cell lines. Results: qRT-PCR analysis revealed significantly higher expression levels of c-Myc LINC01578 in OSCC tissues compared to adjacent tissues( P < 0. 05 ) , confirming that c⁃Myc positively regulates LINC01578 expression. Consistent with sequencing data , c⁃Myc overexpression markedly upregulated LINC01578 (P < 0. 001) , while c⁃Myc knockdown led to a significant decrease in LINC01578 levels(P < 0. 000 1) . Dual lu ciferase reporter gene assays demonstrated that c⁃Myc directly targets and transcriptionally enhanced LINC01578 ex⁃ pression(P < 0. 001) . Seahorse experiments indicated that c⁃Myc promoted glucose metabolism in OSCC through LINC01578 regulation(P < 0. 05) . Colony formation assays showed that LINC01578 overexpression enhanced OS⁃ CC cell proliferation , whereas LINC01578 knockdown inhibited it. Conclusion c⁃Myc upregulates LINC01578 expression in OSCC cells , thereby modulating glycolysis and promoting cell proliferation.

Objective:To investigate and validate the performance of a dosiomics model that utilized 3D dose distribution to forecast radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 3578 patients diagnosed with NPC admitted to Jiangsu Cancer Hospital from January 2011 to December 2021 were retrospectively analyzed. According to the inclusion and exclusion criteria, 97 NPC patients who developed RTLI were assigned into the case group. A 1:1 propensity score matching (PSM) method was used to match 97 NPC patients without RTLI as the control group. Patients were assigned into the training cohort ( n=135) and the validation cohort ( n=59) at a 7:3 ratio by simple random method. Dosiomics features were extracted from the patients' three-dimensional dose distribution maps. Spearman rho and the least absolute shrinkage and selection operator regression were used to select dosiomics features. Clinical features were collected and screened by univariate and multivariate analyses. Eight machine learning classifiers were then trained to build dosiomics models and clinical models, respectively. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to compare the predictive performance of the dosiomics and clinical models. Multivariate analysis was conducted using logistic regression to assess the influencing factors, while comparisons of the ROC curves between two different models were performed using the DeLong test. Results:A total of 1130 dosiomics features were extracted from the three-dimensional dose distribution maps, and 14 features were retained for model building after feature selection. The model based on the support vector machine (SVM) classifier achieved the highest AUC value of 0.977 (95% CI: 0.949-1.000) in the validation cohort, with an AUC of 1.000 (95% CI: 1.000-1.000) in the training cohort. By conducting univariate and multivariate analyses of the patients' clinical features, 2 clinical features were retained to build the clinical model. The model based on the SVM classifier achieved the optimal AUC value of 0.667 (95% CI: 0.523-0.810) in the validation cohort, with an AUC of 0.804 (95% CI: 0.730-0.878) in the training cohort. DeLong test showed that the difference between the dosiomics and clinical models was statistically significant ( P<0.05). Conclusion:The dosiomics model based on 3D dose distribution yields high predictive performance for RTLI in NPC patients after IMRT, which surpasses the clinical feature model, providing a new approach for early clinical prediction of RTLI.

BACKGROUND:Topical administration of tranexamic acid can be used for anti-skin pigmentation,but its large polarity makes it difficult to break through the cuticle barrier and cell membrane when administered topically,and the subcutaneous accumulation concentration is not easy to reach the effective therapeutic concentration.OBJECTIVE:To design functionalized self-assembled micelles to enhance the anti-pigmentation effect of tranexamic acid.METHODS:The plant polyphenol derivative epigallocatechin gallate palmitate and metformin were used as carrier materials.The self-assembled micelles with synergistic anti-pigging activity and enhanced drug permeability were prepared by hydrogen bonding and electrostatic interaction.The nanoscale properties and stability of self-assembled drug-loaded micelles were tested,and their transdermal permeability was evaluated,and their biocompatibility and cellular effects were investigated.RESULTS AND CONCLUSION:(1)Functional self-assembled drug-carrying micelles with average particle size of(176.27±5.23)nm,polydispersity coefficient of 0.23±0.02,and the Zeta potential of(-25.67±0.98)mV had good stability.The mass concentrations of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(20.03±0.12)and(6.67±0.08)mg/mL,respectively.The drug loadings of tranexamic acid and metformin in the self-assembled drug-carrying micelles were(19.97±0.12)％and(6.65±0.08)％,respectively.(2)In vitro transdermal results showed that the self-assembled drug-carrying micelles had higher penetration and intradermal retention per unit skin area,and could penetrate and diffuse to deeper parts of the skin.(3)MTT assay results demonstrated that undrug-loaded self-assembled micelles containing tranexamic acid 50-250 μg/mL had no toxic effects on mouse fibroblasts and mouse skin melanoma cells.The self-assembled drug-carrying micelles containing tranexamic acid 500 μg/mL had a slight toxic effect on mouse skin melanoma cells.The self-assembled drug-carrying micelles containing 50-500 μg/mL of tranexamic acid did not cause hemolysis and had good biological safety.(4)In vitro cell culture results showed that self-assembled drug-carrying micelles containing 500 μg/mL tranexamic acid could significantly inhibit the tyrosinase activity and melanin release of mouse skin melanoma cells,and the inhibitory effect was stronger than that of tranexamic acid solution or metformin solution alone.These results indicated that functionalized self-assembled micelles could synergize with tranexamic acid to inhibit tyrosinase activity,reduce melanin synthesis,and enhance the anti-skin pigmentation effect of tranexamic acid.

Objective:To investigate and validate the performance of a dosiomics model that utilized 3D dose distribution to forecast radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 3578 patients diagnosed with NPC admitted to Jiangsu Cancer Hospital from January 2011 to December 2021 were retrospectively analyzed. According to the inclusion and exclusion criteria, 97 NPC patients who developed RTLI were assigned into the case group. A 1:1 propensity score matching (PSM) method was used to match 97 NPC patients without RTLI as the control group. Patients were assigned into the training cohort ( n=135) and the validation cohort ( n=59) at a 7:3 ratio by simple random method. Dosiomics features were extracted from the patients' three-dimensional dose distribution maps. Spearman rho and the least absolute shrinkage and selection operator regression were used to select dosiomics features. Clinical features were collected and screened by univariate and multivariate analyses. Eight machine learning classifiers were then trained to build dosiomics models and clinical models, respectively. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to compare the predictive performance of the dosiomics and clinical models. Multivariate analysis was conducted using logistic regression to assess the influencing factors, while comparisons of the ROC curves between two different models were performed using the DeLong test. Results:A total of 1130 dosiomics features were extracted from the three-dimensional dose distribution maps, and 14 features were retained for model building after feature selection. The model based on the support vector machine (SVM) classifier achieved the highest AUC value of 0.977 (95% CI: 0.949-1.000) in the validation cohort, with an AUC of 1.000 (95% CI: 1.000-1.000) in the training cohort. By conducting univariate and multivariate analyses of the patients' clinical features, 2 clinical features were retained to build the clinical model. The model based on the SVM classifier achieved the optimal AUC value of 0.667 (95% CI: 0.523-0.810) in the validation cohort, with an AUC of 0.804 (95% CI: 0.730-0.878) in the training cohort. DeLong test showed that the difference between the dosiomics and clinical models was statistically significant ( P<0.05). Conclusion:The dosiomics model based on 3D dose distribution yields high predictive performance for RTLI in NPC patients after IMRT, which surpasses the clinical feature model, providing a new approach for early clinical prediction of RTLI.

Objective:To clarify the medical security plan and its practical effects at the main venue of the 19th Hangzhou Asian Games.Methods:The plan described the medical security implementation plan of the main venue of the 19th Asian Games in Hangzhou (organizational management and operation mechanism, medical security operation system, standardized training and support processes, application of Asian Games intelligent first aid security system, and so on). And through high-facticity simulation verify the operation effect of the main venue's medical support (team mode and response time). Finally, the feasibility and effectiveness of the medical security program verified through the effect of medical services (quantity, disease types, transfers, etc.) during the Asian Games and Asian Paralympic Games.Results:The medical security team of the main venue of the 19th Hangzhou Asian Games included the management team and the operation team, of which consisted of 44 medical staffs (22 doctors and 22 nurses); and were deployed to 16 different security positions. It was also accompanied with 16 volunteers to assist medical staff to transport patients. In addition, a total of 300 medical observers were enrolled in audience area to assist rapid identification, intervention, and collaborative diagnosis and treatment with the medical team. Medical security teams were arranged to cover all the audience areas who can arrive at the patient's area within 2 minutes after receiving orders, transfer the patient to the ambulance’s site in 8 minutes, and transport the patient to a designated hospital within 10-20 minutes. During the Asian Games and Asian Paralympic Games, the medical-care team treated a total of 3 742 patients, including 9 patients transported from medical service sites of the audience area to the stadium infirmary, as well as 83 patients referred to the designated hospital.Conclusions:The medical security implementation plan for the main venues of the Asian Games provides good medical security for the Asian Games and Asian Paralympic Games. It also provides theoretical and practical experience for the development of the medical security system for international events in future.

Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.

Objective:To determine the clinical application value of transcranial sonography (TCS) in the diagnosis of attention deficit hyperactivity disorder (ADHD) in children.Methods:A total of 50 children aged 6-12 years diagnosed with ADHD (ADHD group) and 45 age-matched healthy children (control group) who presented to Suzhou Municipal Hospital and Children′s Hospital of Soochow University from August 2021 to August 2022 were prospectively enrolled for TCS examination. ADHD was diagnosed in accordance with the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-Ⅴ) criteria established by the American Psychiatric Association.Based on clinical symptom characteristics, ADHD was further classified into 3 subtypes, including 14 cases of predominantly inattentive, 3 cases of predominantly hyperactive/impulsive, and 33 cases of combined presentation. The substantia nigra(SN) hyperechoic area and the ratio of SN hyperechoic area to midbrain area (S/M) were measured and compared between the two groups. The examination of the correlation was performed between SN hyperechoic area, S/M ratio, and DSM-Ⅴ scores within the ADHD group.Results:Semi-quantitative analysis: the proportion of the SN grade Ⅲ or more in ADHD group was significantly higher than that in control group [96.00%(48/50) vs 13.3%(6/45), P<0.05]. Quantitative analysis: the area of SN hyperechogenicity and the ratio of S/M were significantly larger in ADHD group than in control group [0.32(0.22, 0.38)cm 2 vs 0.00(0.00, 0.00)cm 2, 7.08(5.11, 8.75)% vs 0.00(0.00, 0.00)%, all P<0.05]. Correlation analysis: The SN hyperechoic area and S/M ratio showed no significant correlations with DSM-Ⅴ scores in the ADHD group ( r=0.144, 0.142, all P>0.05). Conclusions:TCS can detect the SN echo enhancement of ADHD children, and the proportion of SN echo enhancement, SN hyperechoic area and S/M ratio are significantly higher than those of normal children, but the SN hyperecho area and S/M ratio are not significantly correlated with DSM-Ⅴ scores.

Objective To explore the potential categories and influencing factors of the fear of progression in patients with inflammatory bowel diseases(IBD).Methods IBD patients who received inpatient treatment in a tertiary hospital in Nanjing from July 2022 to July 2023 were selected as the study subjects by convenience sampling method.The General Demographic Information Questionnaire,the Chinese version of the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the Chinese version of Inflammatory Bowel Disease Self-efficacy Scale(IBD-SES),and Social Support Rating Scale(SSRS)were administered to the participants.We applied one-way ANOVA and Logistic regression analysis to identify the factors associated with the potential categories of the fear of progression.Results A total of 303 retumed questionnaires(out of the 310)were valid,resulting an effective response rate of 97.74％.According to the results of latent profile analysis,we classified the respondents into 3 categories by the fear of progression,namely"low risk fear of disease adaptation group"(n=127,41.91％),"medium risk fear of illness distress group"(n=139,45.88％),"high risk fear of dysfunction group"(n=37,12.21％).3 groups showed statistically significant differences in permanent address,self-rated financial pressure,current disease status and self-efficacy(P＜0.05).Conclusion Patients with IBD had obvious differences in characteristics on the fear of progression.Nursing personnel should formulate personalized intervention strategies based on the classification characteristics of the fear of progression of IBD patients.Moreover,nurses should focus on improving patients'self-efficacy and promoting patients to treat medical care,stress and emotion management correctly.