Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and the malignant area had a normal"Y"content.After gonadal resection,AMH levels significantly dropped from 7.28 pmol/L to＜0.07 pmol/L.Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum,most with features of Turner syndrome,and female phenotypes are at risk of gonadal tumors.Conclusions In the diagnosis of difficult cases of sex development disorders,when performing peripheral blood karyotype testing,the number of counted cells and analyzed cells should be increased as much as possible,and multi-germ layer cell sampling should be performed.Gonads with a high"Y"mosaic rate are more prone to malignancy in the abdominal cavity.Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P＜0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.

Objective To analyze effects of caragliflozin and empagliflozin on inflammatory markers,glucose and lipid metabolism and miR-144 expression in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 obese T2DM patients admitted to our hospital from June 2021 to May 2024 were selected and divided into the caragliflozin group and the empagliflozin group by random number table method.The two groups were treated with canagliflozin and empagliflozin on the basis of conventional treatment for 6 months.The inflammatory indicators,glucose metabolism indicators,lipid metabolism indicators,microRNA-144(miR-144)expression,body mass index(BMI),clinical efficacy and incidence of adverse reactions were compared between the two groups.Results After a total of 7 cases were excluded during the treatment period,there were 71 cases in the caragliflozin group and 70 cases in the empagliflozin group.After treatment,the levels of tumor necrosis factor-α,interleukin-6,C-reactive protein,fasting blood glucose(FBG),2 h postprandial blood glucose(2 h-PPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol,low density lipoprotein cholesterol,BMI and miR-144 expression were lower than those before treatment in two groups of patients(P＜0.05),and the levels of FBG,2 h-PPG,HbA1c,TG and miR-144 expression were lower in the caragliflozin group than those of the empagliflozin group(P＜0.05).After treatment,high density lipoprotein cholesterol was higher than that before treatment in the two groups(P＜0.05),and that in the canagliflozin group was higher than the empagliflozin group(P＜0.05).There were no significant differences in the clinical efficacy and incidence of adverse reactions between the two groups after treatment(P＞0.05).Conclusion Both caragliflozin and empagliflozin have certain therapeutic efficacy and good safety for obese T2DM patients,and caragliflozin is more effective in improving glucose and lipid metabolism.

Objective To analyze effects of caragliflozin and empagliflozin on inflammatory markers,glucose and lipid metabolism and miR-144 expression in obese patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 obese T2DM patients admitted to our hospital from June 2021 to May 2024 were selected and divided into the caragliflozin group and the empagliflozin group by random number table method.The two groups were treated with canagliflozin and empagliflozin on the basis of conventional treatment for 6 months.The inflammatory indicators,glucose metabolism indicators,lipid metabolism indicators,microRNA-144(miR-144)expression,body mass index(BMI),clinical efficacy and incidence of adverse reactions were compared between the two groups.Results After a total of 7 cases were excluded during the treatment period,there were 71 cases in the caragliflozin group and 70 cases in the empagliflozin group.After treatment,the levels of tumor necrosis factor-α,interleukin-6,C-reactive protein,fasting blood glucose(FBG),2 h postprandial blood glucose(2 h-PPG),glycosylated hemoglobin(HbA1c),triglyceride(TG),total cholesterol,low density lipoprotein cholesterol,BMI and miR-144 expression were lower than those before treatment in two groups of patients(P＜0.05),and the levels of FBG,2 h-PPG,HbA1c,TG and miR-144 expression were lower in the caragliflozin group than those of the empagliflozin group(P＜0.05).After treatment,high density lipoprotein cholesterol was higher than that before treatment in the two groups(P＜0.05),and that in the canagliflozin group was higher than the empagliflozin group(P＜0.05).There were no significant differences in the clinical efficacy and incidence of adverse reactions between the two groups after treatment(P＞0.05).Conclusion Both caragliflozin and empagliflozin have certain therapeutic efficacy and good safety for obese T2DM patients,and caragliflozin is more effective in improving glucose and lipid metabolism.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P＜0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

Objective To explore the effect of circFAT1 on myocardial injury in rats with diabetic cardiomyopathy(DCM)and the regu-latory mechanism of circFAT1 on the miR-211-5p/CCND2 axis.Methods A DCM rat model was established by injecting rats with high glucose and high fat feed combined with STZ.The rats were randomly separated into DCM,circ-NC,circFAT1,circFAT1+agomir-NC,and circFAT1+miR-211-5p agomir groups,with 20 rats in each group;rats fed regular feed were used as control.Real-time PCR was used to detect the levels of circFAT1,miR-211-5p,and CCND2in myocardial tissue and Western blotting was used to detect CCND2 expression in myocardial tissue.The levels of fasting blood glucose(FBG),total cholesterol(TC),and triglycerides(TG)of rats were recorded.Car-diac ultrasound was used to detect the cardiac function of rats.Furthermore,HE and Masson staining were used to observe the pathological morphology of myocardial tissue and TUNEL staining was used to detect myocardial apoptosis.Additionally,ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Double luciferase reporter gene assay was used to verify the targeting relationship among circFAT1,miR-211-5p,and CCND2.Results Compared with the control group,the expression of circFAT1 and CCND2mRNA and protein and the levels of LVEF and LVFS decreased in the DCM group(P<0.05)whereas,the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-αincreased(P<0.05).Compared with the DCM group,the levels of circFAT1,CCND2mRNA and protein,LVEF,and LVFS increased in the circFAT1 group(P<0.05),whereas the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-α decreased(P<0.05).Furthermore,miR-211-5p agomir reversed the protective effect of circFAT1 on DCM myocardial injury,and the expression of CCND2mRNA and protein decreased(P<0.05).Conclu-sion circFAT1 alleviates myocardial tissue damage in rats with DCM by regulating the miR-211-5p/CCND2 axis.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.