The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Objective To study the effect of curcumin on osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)in high glucose condition and its mechanism.Methods The cultured hBMSCs were divided into the normal group,high glucose group,and high glucose+curcumin group.The early osteogenic differentiation level of the cells in each group was assessed by detecting alkaline phosphatase(ALP)activity.Alizarin red staining was used to evaluate the formation of mineralized nodules in the late stage of osteo-genic differentiation.The expression of osteogenic-related genes,including Runt-related transcription factor 2(Runx2),osteocalcin(OCN),and type Ⅰ collagen(COL-1),was detected by RT-PCR after 21 days of osteogenic induction.Western blot was used to detect the expression of heme oxygenase-1(HO-1)in each group.Furthermore,an HO-1 small interfering RNA(siRNA)model was constructed and its interference efficiency was assessed.The expression levels of osteogenesis-related proteins(Runx2,OCN,and COL-1)between the high glucose+curcumin group and high glucose+curcumin+siHO-1 group were compared.Results Compared with the normal group,the high glucose group showed decreased ALP activity,reduced formation of mineralized nodules,decreased expression of osteogenic-related genes(Runx2,OCN,and COL-1),and inhibited expression of HO-1(P＜0.05).Compared with the empty vector group,the siHO-1 group showed significantly reduced expression of HO-1 in cells,indicating successful siRNA interference(P＜0.01).Compared with the high glucose+curcumin group,the expression levels of osteogenesis-related proteins(OCN,COL-1,and Runx2)were all decreased in the high glucose+curcumin+siHO-1 group(P＜0.05).Conclusion Curcumin can promote osteogenic differentiation of hBMSCs under high glucose environment,which is related to the expression of HO-1.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

Objective To investigate the influence of different delivery techniques,treatment sites and dose-volume algorithms on the results of three-dimensional dosimetric verification for intensity-modulated radiation therapy(IMRT)plans and the importance of individualized quality assurance(QA)evaluation standard for radiotherapy plans.Methods Totally 350 tumor patients receiving radiotherapy at some hospital from January 2017 to February 2022 had their three-dimensional dosimetric verification results of IMRT plans selected retrospectively and underwent data collection with COMPASS system,and then were grouped in terms of delivery technique(fixed-beam IMRT and volumetric modulated arc therapy),treatment site(neck,chest and abdomen)and dose-volume algorithm(anisotropic analytical algorithm and collapsed cone convolution algorithm).All the groups were compared based on the 3％/2 mm criterion with regard to the Gamma pass rate of 10％prescription dose area(GP10％),Gamma pass rate(GP50％)and mean Gamma index(μGI5o％)of 50％prescription dose area,dose of 95％target volume(D95％)and its mean dose(Dmean),parotid gland mean dose(Dmean),dose of 1％spinal cord volume(D1％),dose of 1％brain stem volume(D1％)of head and neck radiotherapy plan,heart and lung mean dose(Dmean)and dose of 1％spinal cord volume(D1％)of chest radiotherapy plan and bladder,rectum and femur mean dose of abdomen radiotherapy plan(Dmean).SPSS 26.0 software was used for statistical analysis.Results For different delivery techniques,significant differences were found in all the QA results except GP50％of abdomen radiotherapy plan(P＜0.05).For different treatment sites,the differences were statistically significant between the QA results of head and neck radiotherapy plan and abdomen plan and between those of chest radio-therapy plan and abdomen radiotherapy plan(P＜0.05),while were not significant between the QA results of head and neck radiotherapy plan and chest radiotherapy plan(P＞0.05).For different dose-volume algorithms,the QA results had significant differences except D5％of abdomen radiotherapy planning target volume and Dmean and D1％of chest radiotherapy PTV(P＜0.05).Conclusion Dosimetric verification results vary depending on the delivery technique,treatment site and dose-volume algorithm.Statistical process control recommended by AAPM TG-218 report may be involved in to establish individualized QA standard for radiotherapy plans in case universal action limits are not appropriate.[Chinese Medical Equipment Journal,2024,45(11):54-59]

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.
Plant Extracts/pharmacology* ; Asteraceae ; Triterpenes ; Sesquiterpenes/pharmacology* ; Anti-Inflammatory Agents ; Phytochemicals/pharmacology*