AIM: To screen the predictors of disease progression risk in patients with diabetic macular edema(DME), establish a joint prediction model and analyze its predictive efficiency.METHODS:A retrospective selection was made of 240 patients with DME who were treated in our hospital from July 2021 to October 2024 as the research subjects. The patients were divided into a low-risk group(n=102)and a high-risk group(n=138)based on the central macular thickness(CMT)and whether the fovea was accumulated. The basic information of the patients and relevant examination data such as glycolipid metabolism indicators and liver and kidney function indicators were collected. The indicators with differences in the univariate analysis(P<0.05)were included in the multivariate analysis to screen out the independent influencing factors of disease progression in DME patients and construct a predictive model. The fitting effect of the prediction model was evaluated by the area under the receiver operating characteristic curve, and the prediction model was verified by sensitivity, specificity and Youden index.RESULTS: The general data of the two groups of patients are comparable, and there was no statistically significant difference in blood pressure between the two groups of patients(both P>0.05). Univariate analysis showed that the glycated hemoglobin(HbA1c), fasting blood glucose(FBG), advanced glycation end products(AGEs), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), serum creatinine(Scr), uric acid(UA), and cystatin C(Cys-C)at 3 and 6 mo in the high-risk group at baseline, 3 and 6 mo were higher than those in the low-risk group(all P<0.01). The baseline, 3 and 6 mo estimated glomerular filtration rate(eGFR), total bilirubin(TBIL), and 3 and 6 mo high-density lipoprotein cholesterol(HDL-C)in the high-risk group were all lower than those in the low-risk group(P<0.05). Regression analysis showed that baseline HbA1c, 3 mo FBG, 3 mo AGEs, baseline LDL-C, 3 mo TG, 3 mo eGFR, baseline TBIL, and 6 mo TBIL were risk factors for disease progression in DME patients. The area under curve(AUC)of the combined prediction model was 0.909(95%CI: 0.872-0.945), with a sensitivity of 79.00% and a specificity of 94.10%.CONCLUSION: HbA1c, FBG, AGEs, LDL-C, TG, eGFR and TBIL are risk factors for the risk of disease progression in patients with DME. The combined prediction model can provide a reference for predicting the risk of disease progression in patients with DME.

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. Results: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246–0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076–0.8567). Conclusion This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. Results: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246–0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076–0.8567). Conclusion This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. Results: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246–0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076–0.8567). Conclusion This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

OBJECTIVES: To clarify the role of hippocampal glutamate system in regulating HPA axis in mediating the effect of electroacupuncture (EA) at the heart meridian for improving myocardial injury in rats with acute myocardial ischemia (AMI). METHODS: Male SD rats were randomized into sham-operated group, AMI group, EA group, and L-glutamic acid+EA group (n=9). Rat models of AMI were established by left descending coronary artery ligation, and EA was applied at the "Shenmen-Tongli" segment; the rats in L-glutamic acid+EA group were subjected to microinjection of L-glutamic acid into the bilateral hippocampus prior to AMI modeling and EA treatment. Cardiac functions of the rats were evaluated using echocardiography, and ECG and heart rate variation (HRV) were analyzed using PowerLab and LabChart. Pathological changes in the myocardial tissue was examined using HE staining, and serum levels of myocardial enzymes were detected with ELISA. Myocardial expressions of TH and GAP43 were detected with immunohistochemistry, and colocalization of VGLUT1, VGLUT2 and c-fos were observed using immunofluorescence staining; the expressions of VGLUT1, VGLUT2, NMDAR1 and NMDAR2B were detected using Western blotting. RESULTS: The rat models of AMI showed significantly decreased LVEF and LVFS and increased serum levels of myocardial enzymes in positive correlation with the HPA axis. Numerous TH- and GAP43-positive cells were observed in the hippocampus, where the expressions of NE and E, neurons colabeled with VGLUT1, VGLUT2 and c-fos, and expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu increased significantly. All these changes were significantly improved by interventions with EA as compared with those in AMI and L-Glutamate+EA groups. CONCLUSIONS In rats with AMI, EA at the heart meridian can regulate excessive glutamate release in the hippocampus, thereby inhibiting HPA axis hyperactivity and reducing sympathetic nerve activity to protect the myocardial tissue.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Rats ; Glutamic Acid/metabolism* ; Myocardial Ischemia/physiopathology* ; Hypothalamo-Hypophyseal System/physiopathology* ; Pituitary-Adrenal System/physiopathology* ; Receptors, N-Methyl-D-Aspartate/metabolism*

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Objective To investigate the expression and prognostic value of serum receptor for advanced glycation end products(RAGE)and CXC-chemokine ligand 16(CXCL16)in patients with sepsis complicated with acute respiratory distress syndrome(ARDS).Methods A total of 234 patients with sepsis diagnosed and treated in a hospital from January 2019 to January 2022 were selected as the study subjects,and were divided into 82 patients with sepsis complicated with ARDS(ARDS group)and 152 patients with sepsis without ARDS(non-ARDS group)according to whether the subjects were complicated with ARDS.ARDS group was divided into survival group(n=50)and death group(n=32)according to the survival status within 28 days of admission.Another 60 healthy subjects who underwent physical examination in the same period were se-lected as the control group.Serum RAGE and CXCL16 levels were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis of serum RAGE and CXCL16 levels with sequential organ failure assess-ment(SOFA)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score and oxygenation index in patients with sepsis and ARDS.Multivariate Logistic regression analysis of prognostic factors of sep-sis complicated with ARDS.The predictive value of serum RAGE and CXCL16 on the prognosis of sepsis complicated with ARDS patients was analyzed by receiver operating characteristic curve.Results The serum RAGE and CXCL16 levels in ARDS group were higher than those in non-ARDS group and control group,and the serum RAGE and CXCL16 levels in non-ARDS group were higher than those in control group,the differ-ence was statistically significant(P＜0.05).Compared with the survival group,the mechanical ventilation time,intensive care unit stay time,procalcitonin,SOFA score,APACHE Ⅱ score,serum RAGE,CXCL16 lev-els were higher in the death group,and the oxygenation index was lower,with statistical significance(all P＜0.05).The serum RAGE level in patients with sepsis complicated with ARDS was positively correlated with SOFA score and APACHE Ⅱ score(r=0.603,0.671,P＜0.05).Serum CXCL16 levels were positively corre-lated with SOFA score and APACHE Ⅱ score(r=0.655,0.707,P＜0.05).Serum RAGE and CXCL16 were negatively correlated with oxygenation index(r=-0.712,-0.683,P＜0.05).Multi-factor Logistics regres-sion analysis showed that serum RAGE and CXCL16 were independent risk factors for death within 28 days of admission in patients with sepsis complicated with ARDS.The area under the curve(AUC)of combined de-tection of serum RAGE and CXCL16 for predicting death within 28 days of admission in patients with sepsis complicated with ARDS was 0.882,which was higher than that of single index detection of serum RAGE and CXCL16,and the difference was statistically significant(Z=4.450,4.906,P＜0.05).Conclusion The com-bined detection of serum RAGE and CXCL16 is helpful to evaluate the clinical prognosis of sepsis complicated with ARDS patients.

ObjectiveThis study conducted a "6 + 1" clinical comprehensive evaluation of the existing research on Zhichuanling oral liquid （ZOL） in the treatment of asthma，so as to clarify the clinical advantages and precise clinical positioning of ZOL in the treatment of asthma， lay a foundation for further research and academic promotion of ZOL， and provide new directions for patent cultivation. MethodAn evaluation method featuring a qualitative and quantitative combination was used， which considered the dimensions of safety，effectiveness，economy，innovation，suitability，accessibility， and traditional Chinese medicine （TCM） characteristics. According to Expert Meeting Law， relevant weights were obtained through voting. CSC_v2.0 software was used to calculate each dimension and convert it into the corresponding grade score. ResultBased on the existing materials，① ZOL instruction indicates the adverse reactions，taboo， and notes. Multiple data of clinical research before and after marketing and spontaneous reporting system shows that ZOL has controllable risk and good safety. Safety is rated as B grade. ② Multiple data of clinical research before marketing， systematic evaluation of clinical effectiveness， and Meta-analysis shows that ZOL has good effectiveness and clinical significance. Effectiveness is rated as a B grade. ③ Analysis of the cost-effectiveness of ZOL combined with conventional treatment shows that the economy of the drug is good and rated as a B grade. ④ ZOL has better innovation， which is rated as an A grade. ⑤ ZOL can basically meet the clinical drug needs based on the result of the questionnaire survey and has good suitability， which is rated as a B grade. ⑥ ZOL has better accessibility， and accessibility is rated as A grade. ⑦ ZOL involves a rich theory of TCM but insufficient experience of human usage. It is thus rated as a C grade in terms of TCM characteristics. Based on the results of "6 + 1" dimension，the clinical comprehensive evaluation of ZOL in the treatment of asthma （cold syndrome and heat syndrome）is rated as B category. ConclusionZOL has good clinical value and outstanding innovation and accessibility in the treatment of asthma （cold syndrome and heat syndrome）. It is recommended that ZOL be transformed into the relevant policy results of basic clinical drug management procedurally. At the same time，it is recommended to actively cultivate patents with TCM characteristics.