Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Retinopathy of prematurity (ROP) is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia. Here, we investigated the potential effects of alamandine, a novel heptapeptide in the renin-angiotensin system (RAS), on hypoxia-induced retinal neovascularization and its underlying mechanisms. In vivo, the C57BL/6J mice with oxygen-induced retinopathy (OIR) were injected intravitreally with alamandine (1.0 μmol/kg per eye). In vitro, human retinal microvascular endothelial cells (HRMECs) were utilized to investigate the effects of alamandine (10 μg/mL) on proliferation, apoptosis, migration, and tubular formation under vascular endothelial growth factor (VEGF) stimulation. Single-cell RNA sequencing (scRNA-seq) matrix data from the Gene Expression Omnibus (GEO) database and RAS-related genes from the Molecular Signatures Database (MSigDB) were sourced for subsequent analyses. By integrating scRNA-seq data across multiple species, we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group. Next, alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice. In vitro, alamandine effectively mitigated VEGF-induced proliferation, scratch wound healing, and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α (HIF-1α)/VEGF pathway. Further, coincubation with D-Pro⁷ (Mas-related G protein-coupled receptor D (MrgD) antagonist) hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro. Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway, providing a potential therapeutic agent for OIR prevention and treatment.
Animals ; Retinal Neovascularization/prevention & control* ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism* ; Humans ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Oligopeptides/therapeutic use* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Endothelial Cells/drug effects* ; Retinopathy of Prematurity/drug therapy* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Renin-Angiotensin System/drug effects* ; Cells, Cultured

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

In recent years, the prevalence of obstructive coronary artery disease has continued to rise. Despite the widespread application of strategies such as intensive pharmacotherapy, coronary artery bypass grafting, or percutaneous coronary intervention, a subset of patients still experience recurrent angina symptoms, which severely impacts their quality of life. For such cases of refractory angina (RA), researchers domestically and internationally have explored therapeutic approaches such as spinal cord stimulation, transmyocardial laser revascularization, and sympathectomy. However, existing studies are largely limited to small-scale clinical trials, and their clinical translation still faces challenges due to insufficient validation of safety and efficacy. Injectable hydrogels, as functional materials with hydrophilic three-dimensional network structures, demonstrate unique advantages in the treatment of RA. They can not only provide mechanical support but also serve as controlled-release carriers for drugs and proteins, and synergize with gene therapy and stem cell therapy to promotemyocardial tissue repair. This article systematically reviews the application prospects of injectable hydrogels in the treatment of RA, aiming to provide insights for future therapeutic strategies.

OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective:To analyze the influencing factors of platinum resistant recurrence in advanced epithelial ovarian cancer(AEOC),establish a nomogram model to predict platinum-resistant recurrence of AEOC,and inter-nally validate it.Methods:The clinicopathological data of 577 AEOC patients who achieved complete remission af-ter initial treatment in the Department of Gynecology,Yunnan Cancer Hospital from June 1,2013 to December 31,2021 were collected.According to whether the platinum free interval(PFI)was less than 6 months,the patients were divided into platinum-resistant recurrence group(130 cases)and non-platinum-resistant group(447 cases,including patients with platinum-sensitive recurrence and no recurrence after 6 months of follow-up).Multivariate Logistic regression analysis was used to screen for the independent risk factors affecting the recurrence of plati-num-resistant patients.Based on the independent risk factors,a nomogram prediction model was established,and Bootstrap method was used for internal verification.The area under the ROC curve(AUC),calibration curve and decision curve(DCA)were used to evaluate the performance of the model.Results:①There were statistically sig-nificant differences in age,bilateral ovarian invasion,FIGO staging,menopause,neoadjuvant chemotherapy(NACT),chemotherapy interval(TTC),platelet count(PLT),platelet count/lymphocyte count ratio(PLR),fibrino-gen/lymphocyte count ratio(FLR),prognostic nutritional index(PNI),albumin(ALB),CA125 level,ascites volume,residual lesions,perioperative chemotherapy frequency,and CA125 half-life between the two groups(P＜0.05).②Multivariate Logistic regression analysis showed that bilateral ovarian invasion,FIGO stage Ⅳ,TTC＞16 days,ini-tial ascites volume＞1000ml,perioperative chemotherapy frequency＞9 times,surgery with R2 resection,CA125 half-life＞52 days were independent risk factors for recurrence of platinum-resistant AEOC patients(OR＞1,P＜0.05).③The AUC of the nomogram model constructed based on the above 7 indicators was 0.791(95％Cl 0.747-0.835),and the calibration curve and ideal curve fitted well.DCA showed that the net benefit interval of the model was 0.037-0.800.Conclusions:The nomogram prediction model based on independent risk factors for the recurrence of platinum-resistance of AEOC patients has good discrimination,calibration and clinical appli-cability,which can better predict the recurrence risk of platinum-resistance in AEOC patients after the initial treat-ment.

Objective To provide pharmaceutical care for patients with hepatitis B cirrhosis by using the medication therapy management(MTM)model combined with Pharmaceutical Care Network Europe(PCNE),and to analyze the effectiveness of pharmaceutical care from clinical efficacy,safety,humanistic effect and drug-related problems(DRPs).Methods Patients with hepatitis B cirrhosis were randomly divided into the pharmaceutical care group and the control group who received only conventional treatment.Clinical pharmacists used MTM combined with PCNE to provide pharmaceutical care in the pharmaceutical care group.Economic effects,clinical indicators,safety,medication compliance and quality of life were compared between the two groups during the treatment and follow-up period.DRPs were analyzed in the pharmaceutical care group.Results The cost-utility ratio and clinical indicators in the pharmaceutical care group were better than those in the control group,and the adverse drug reactions of the former were statistically significant compared with the latter at the three months follow-up,and medication compliance and quality of life were statistically significant after intervention and during follow-up(P＜0.05).There were 52 DRPs in the pharmaceutical care group,mainly in the category of poor treatment outcome.The main reasons were poor drug selection and excessive usage and dosage.There were 46 DRPs accepted by intervention,and 45 DRPs were completely and partially solved.Conclusion The pharmaceutical care model of MTM combined with PCNE classification system for patients with hepatitis B cirrhosis played a positive role in the treatment and follow-up period.

Objective:To investigate the effects of modified endoscopic retrograde appendicitis therapy (mERAT) on the treatment of children with different severities of acute appendicitis.Methods:This study was a case-control study. A total of 586 children with acute appendicitis, who were admitted to the Pediatric Department of Second Affiliated Hospital of Air Force Medical University between January 2019 and November 2023, were selected as the research subjects. According to the severity of the disease, the patients were divided into simple appendicitis group, suppurative appendicitis group and perforated appendicitis group. The baseline data, hospitalization treatment and costs, outcomes, and recurrence in each group were analyzed, and the difference in the effectiveness of mERAT between the groups were compared by Kruskal-Wallis H test and χ2 test. Results:Among 586 children, there were 338 males and 248 females. The age at onset was 7.0 (4.6, 9.4) years. There were 475 cases of simple appendicitis, 78 cases of suppurative appendicitis, and 33 cases of perforated appendicitis. There were no significant differences in age and gender among the three groups ( F=0.59, χ2=3.31, both P>0.05). However, there were statistically significant differences in body temperature, white blood cell counts, neutrophil percentage, lymphocyte percentage, nausea or vomiting, right lower abdominal pain, umbilical pain, right lower abdominal tenderness, and right lower abdominal rebound pain ( H=7.56, 161.52, 169.11, and 169.61, χ2=12.05, 13.82, 12.05, 7.74, 20.35, and 94.61, all P<0.05). Also, the treatment time, postoperative hospital stay, total hospital stay, and cost showed statistically significant differences ( H=4.70, 33.66, 34.99, 30.37, all P<0.05). There was no significant difference in the initial treatment success rate (98.1% (466/475) vs. 98.7% (77/78) vs. 90.9% (30/33), P=0.057). During the 30 (23, 36) months of follow-up, the recurrence rate was 7.9% (35/433) in the simple appendicitis group, 20.8% (15/72) in the suppurative appendicitis group, and 30.0% (9/30) in the perforated appendicitis group, with a statistically significant difference ( χ2=23.56, P<0.001). Among the children with recurrent appendicitis, 15 cases still chose mERAT, of them 11 cases (31.2%) had simple appendicitis, 2 cases (2/15) had suppurative appendicitis, and 2 cases (2/9) had perforated appendicitis.The latest time to recurrence in the 3 groups was 32, 35 and 10 months, respectively. Conclusion:Treatment with mERAT has a good effect in pediatric simple appendicitis, but has a higher recurrence rate despite a better initial treatment success rate in suppurative appendicitis and perforated appendicitis.