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Background: Antioxidant therapy aimed at reducing excessive local oxidative stress is one of the most important strategies for promoting diabetic wound repair. The reversible transformation of Ce 3+ /Ce 4+ in ceria (CeO 2 ) can reduce excessive local oxidative stress. However, inducing angiogenesis, local anti-inflammatory effects, and other positive effects are challenging. Therefore, ideal dressings for chronic diabetic wound management must concurrently reduce excessive oxidative stress, promote angiogenesis, and have anti-inflammatory effects. Methods: In this study, Ce-doped borosilicate bioactive glasses (BGs) were prepared using the sol-gel method, and CeO 2 nanocrystals (CeO 2 -NCs) were precipitated on the glass surface by heat treatment to obtain BG- x Ce composite glass nanospheres. Subsequently, nanospheres were modified by amino group and combined with dopamine and acrylamide to obtain BG- x Ce/polydopamine/polyacrylamide (PDA/PAM) composite hydrogel. Then, the morphology and properties of composite hydrogels were detected, and the properties to treat the diabetic wounds were also evaluated. Results: The results demonstrated that the BG-10Ce/PDA/PAM composite hydrogel possessed excellent tensile and adhesive properties. In vitro, the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) and fibroblasts (L929) were enhanced by reducing reactive oxygen species (ROS) levels in the conditioned medium. Animal experiments have shown that CeO 2 -NCs in hydrogels effectively scavenge ROS in diabetic wounds, and Sr dissolved from the glassy phase can modulate macrophage polarization to the M2 phenotype. Conclusions: The synergistic effect of both amorphous materials and nanocrystals provides the BG-10Ce/PDA/PAM composite hydrogel with great potential for diabetic wound healing., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Muyan Qin et al.)

Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture., Methods: Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases., Results: A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3-8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4-34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p < 0.001), larger pseudoaneurysm diameter (8.1 ± 3.2 mm vs. 6.0 ± 2.3 mm, p = 0.012), higher incidence of pulmonary cavitation (76.2% vs. 44.8%, p = 0.027), and larger cavitation diameters (32.9 ± 18.8 mm vs. 15.7 ± 8.4 mm, p = 0.005). The mean pulmonary artery pressure (mPAP) in the ruptured group was also significantly higher than that in the unruptured group [23.9 ± 7.4 mmHg vs. 19.2 ± 5.0 mmHg, p = 0.011]. Endovascular treatment was successfully performed in all 21 patients with ruptured PAP, of which the clinical success rate was 96.0%. Five patients experienced recurrent hemoptysis within one year., Conclusions: Massive hemoptysis, pseudoaneurysm diameter, pulmonary cavitation, and elevated mPAP were the risk factors for rupture of pseudoaneurysm. Our findings facilitate early identification and timely intervention of PAP at high risk of rupture., (© 2024. The Author(s).)

Background: Lymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expression in tumors and patient prognosis, indicating the need for further investigation into the significance of LAG-3 expression levels in tumor therapies. In this study, 68 Ga-NOTA-XH05, a novel peptide-based positron emission tomography (PET) tracer targeting LAG-3, was constructed to non-invasively detect LAG-3 expression in melanoma after CpG oligonucleotide (CpG) treatment and explore the relationship between LAG-3 expression and therapeutic effect., Methods: The tracer 68 Ga-NOTA-XH05 was identified by high-performance liquid chromatography after being prepared and purified. Cell uptake and blocking essays were performed to verify the specificity of the tracer in vitro. The expression of LAG-3 in B16-F10 subcutaneous tumors was monitored by flow cytometry, and its correlation with the tracer uptake was analyzed to evaluate the tracer specificity. PET imaging and biodistribution studies were conducted after CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumor models to assess the ability of 68 Ga-NOTA-XH05 in monitoring immunotherapy efficacy and the abscopal effect of CpG., Results: Following purification, 68 Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis revealed a positive correlation between LAG-3 expression in tumors and the uptake of 68 Ga-NOTA-XH05. In B16-F10 bearing mice treated with CpG, PET imaging using 68 Ga-NOTA-XH05 demonstrated a higher tumor to blood ratio (TBR) compared with the control group. Furthermore, TBR values obtained from CpG-treated mice allowed for differentiation between responders and non-responders. In a bilateral subcutaneous tumor model where only right-sided tumors were treated with intratumoral injection of CpG, TBR values of left-sided tumors were significantly higher than those in the control group, indicating that 68 Ga-NOTA-XH05 could effectively monitor the systemic effect of local CpG injection., Conclusion: Our findings highlight the detection capability of 68 Ga-NOTA-XH05 in assessing LAG-3 expression levels within tumors and evaluating response to immunotherapy, thereby suggesting promising clinical translational prospects., Competing Interests: Competing interests: None Declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immunotherapy shows great therapeutic potential for long-term protection against tumor relapse and metastasis. Innate immune sensors, such as cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), dissolve DNA and induce type I interferon. Through activation of the cGAS/STING pathway, chemotherapy drugs and reversine (REV) may provide synergetic anti-tumor effects. Here, we prepared drug-loaded cell membrane hybrid lipid nanovesicles (LEVs) (designated LEV@DOX@REV) by fusion of cell membranes, phospholipids, doxorubicin (DOX), and REV, to realize accurate delivery to tumors and chemo-immunotherapy. The cell membranes of LEVs confer "homing" abilities. DOX can induce immunogenic cell death as a result of its specific immunomodulatory effects, which promotes the maturation of immune cells and improves the microenvironment of the immune system. REV is proven to efficiently activate cGAS/STING signaling, thereby enhancing the immune system. The antitumor efficacy of LEV@DOX@REV was evaluated in a 4T1 subcutaneous tumor xenograft model, a distant metastatic tumor model, and a liver metastatic tumor model. LEV@DOX@REV facilitated the infiltration of cytotoxic T lymphocytes within tumors, increased the secretion of proinflammatory cytokines, and modified the tumor microenvironment. In conclusion, LEV@DOX@REV displayed favorable antitumor effects and extended the survival of tumor-bearing mice. We therefore successfully developed nanoparticles capable of enhancing immune activation that have potential therapeutic applications for cancer immunotherapy., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Ruijie Qian et al.)

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing., (© 2024 Wiley‐VCH GmbH.)

Intense warming profoundly alters precipitation phase patterns and intensity in High Mountain Asia (HMA). While snowfall climatology and precipitation extremes have been studied, there is a lack of understanding of snowfall extremes within HMA. Here, we investigate the spatial and temporal variability of non-extreme and extreme snowfall in hydrological years 1979-2020 using multi-source meteorological data, compare weather systems during extreme and non-extreme snowfall events, and identify key circulation factors that influence fluctuations in mean annual snowfall and extreme snowfall. The snowfall amount (-0.13 d/mm), days (-0.56 d/a), and fraction (-0.0012) were significantly reduced in HMA, with a shorter snowfall season (-0.52 d/a). Some extreme snowfall metrics (maximum 1-day snowfall and maximum 3-day snowfall) were insensitive to climate change, whereas the maximum consecutive snowfall days (-0.007 d/a), snowfall amount (-0.0023 mm/a), heavy snowfall days (S95pD; 0.0087 d/a), and extremely heavy snowfall days (S99pD; -0.1019 d/a) showed significant decreases. Synthetic analyses show that extreme snowfall events were more likely to occur within a narrow temperature range (-5 °C to 3 °C) with higher relative humidity and precipitation compared to non-extreme events. A stepwise regression method was used to determine that the fluctuation in the average annual snowfall was closely related to the Atlantic Multidecadal Oscillation, whereas the variation in extreme snowfall was mainly influenced by the Southern Oscillation Index. Our research provides a reference for assessing the potential impacts of climate change on a regional scale for risk management and disaster adaptation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biofilm-related infections (BRIs) present significant challenges owing to drug resistance, adverse immune responses, and implant failure; however, current approaches inadequately cater to the diverse therapeutic requirements at different stages of infection. To address this issue, a multi-immunotherapy strategy in combination with sonodynamic therapy is proposed for the chronological treatment of BRIs. Macrophage membrane-decorated targeting sonosensitive nanoadjuvants are fabricated to load cytosine-phosphate-guanine oligodeoxynucleotide (CPG-ODN) or microRNA (miR)-21-5p. In the early stages of BRI (Stage I), CPG-ODN-loaded nanoadjuvants (CPG@HMPN@M) promote the formation of neutrophil extracellular traps to capture and neutralize detached microbes. During the late stage of infection (Stage II), CPG-ODNs redirect macrophage polarization into the M1 phase to combat infections via TLR9/Myd88/TRAF6 pathway. During these stages, CPG@HMPN@M generates singlet oxygen through sonodynamic processes, eradicating the biofilms under US irradiation. Once the BRIs are eliminated, miR-21-5p-loaded nanoadjuvants (miR@HMPN@M) are delivered to the lesions to suppress excessive inflammation and promote tissue integration by evoking macrophage M2 polarization during the repair phase (Stage III) through PTEN/PI3K/Akt pathway. This innovative approach aims to provide comprehensive treatment strategies for the chronological treatment of BRI by effectively eliminating infections, promoting tissue restoration, and implementing different immune regulations at different stages, thus demonstrating promising clinical value., (© 2023 Wiley-VCH GmbH.)

Myocardial infarction (MI) resulting from coronary artery occlusion is the leading global cause of cardiovascular disability and mortality. Anti-inflammatory treatment plays an important role in MI treatment. Triptolide (TPL), as a Chinese medicine monomer, has a variety of biological functions, including anti-inflammatory, anti-tumor, and immunoregulation. However, it has been proved that TPL is poorly water soluble, and has clear hepatotoxicity and nephrotoxicity, which seriously limits its clinical application. Herein, we designed a long-acting hydrogel platform (TPL@PLGA@F127) for MI treatment by intramyocardial injection. First, we found that the inflammatory response and immune regulation might be the main mechanisms of TPL against MI by network pharmacology. Subsequently, we prepared the hydrogel platform (TPL@PLGA@F127) and tested its effects and toxicity on normal organs in the early stage of MI (3 days after MI-operation). The results showed that TPL@PLGA@F127 could not only promote "repair" macrophages polarization (to M2 macrophage) by day 3 after MI, but also has a long-lasting anti-inflammatory effect in the later stage of MI (28 days after MI-operation). Additionally, we proved that TPL@PLGA@F127 could attenuate the toxicity of TPL by releasing it more slowly and stably. Finally, we observed the long-term effects of TPL@PLGA@F127 on MI and found that it could improve cardiac function, depress the myocardial fibrosis and protect the cardiomyocytes. In summary, this study indicated that TPL@PLGA@F127 could not only enhance the therapeutic effects of TPL on MI, but also attenuate the hepatotoxicity and nephrotoxicity, which established a strong foundation for the clinical application of TPL for MI., (© 2023. The Author(s).)

Element doping is a prominent method for reducing the lattice thermal conductivity and optimizing the thermoelectric performance of materials in the thermoelectric field. However, determination of the thermal conductivity of element-doped systems is a challenging task, especially when the elements are randomly doped. In this work, a first-principles based deep neural network potential (NNP) is developed to investigate the lattice thermal transport properties of Cr-doped Sb 2 Te 3 using molecular dynamics simulations. Compared with pure Sb 2 Te 3 , the thermal conductivity of orderly Cr-doped Sb 2 Te 3 with Cr atoms locating at specific atomic layer positions decreases slightly in the in-plane direction, but sharply in the out-of-plane direction. The decrease of the low frequency phonon density of states and the enhancement of phonon scattering near 2.5 THz are the primary reasons for the decrease in the thermal conductivity of Cr-doped Sb 2 Te 3 , while the decrease of phonon velocity due to band flattening is the reason for the sharp decrease of thermal conductivity in the out-of-plane direction. Moreover, the thermal conductivities of randomly Cr-doped Sb 2 Te 3 with different Cr concentrations are also investigated using the NNP. It is found that the thermal conductivities in both the in-plane and out-of-plane directions are reduced by 76% and 80%, respectively, for Sb 36 Cr 36 Te 108 . Furthermore, the influence of different Cr dopant arrays on the thermal conductivity of Sb 2 Te 3 is also predicted using the NNP. Our work provides a good example for predicting the thermal conductivity of element-doped systems using the NNP combined with molecular dynamics simulations.

Background: Accumulating studies have demonstrated that elevated TIGIT expression in tumor microenvironment correlates with better therapeutic response to TIGIT-based immunotherapy in pre-clinical studies. Therefore, a non-invasive method to detect tumor TIGIT expression is crucial to predict the therapeutic effect., Methods: In this study, a peptide-based PET imaging agent, 68 Ga-DOTA- D TBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. D TBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with 68 Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of 68 Ga-DOTA- D TBP-3 to TIGIT and its stability in fetal bovine serum. In vivo studies were assessed by micro-PET, biodistribution, and immunohistochemistry on tumor-bearing BALB/c mice., Results: The in vitro studies showed the equilibrium dissociation constant of 68 Ga-DOTA- D TBP-3 for TIGIT was 84.21 nM and its radiochemistry purity was 89.24 ± 1.82% in FBS at 4 h in room temperature. The results of micro-PET, biodistribution and immunohistochemistry studies indicated that 68 Ga-DOTA- D TBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h., Conclusion: 68 Ga-DOTA- D TBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade., (© 2023. The Author(s).)

Inflammatory regulation induced by macrophage polarization is essential for cardiac repair after myocardial infarction (MI). Berberin (BBR) is an isoquinoline tetrasystemic alkaloid extracted from plants. This study analyzes the most likely mechanism of BBR in MI treatment determined via network pharmacology, showing that BBR acts mainly through inflammatory responses. Because platelets (PLTs) can be enriched in the infarcted myocardium, PLT membrane-coated polylactic-co-glycolic acid (PLGA) nanoparticles (BBR@PLGA@PLT NPs) are used, which show enrichment in the infarcted myocardium to deliver BBR sustainably. Compared with PLGA nanoparticles, BBR@PLGA@PLT NPs are more enriched in the infarcted myocardium and exhibit less uptake in the liver. On day three after MI, BBR@PLGA@PLT NPs administration significantly increases the number of repaired macrophages and decreases the number of inflammatory macrophages and apoptotic cells in infarcted rat myocardium. On the 28th day after MI, the BBR@PLGA@PLT group exhibits a protective effect on cardiac function, reduced cardiac collagen deposition, improved scar tissue stiffness, and an excellent angiogenesis effect. In addition, BBR@PLGA@PLT group has no significant impact on major organs either histologically or enzymologically. In summary, the therapeutic effect of BBR@PLGA@PLT NPs on MI is presented in detail from the perspective of the resolution of inflammation, and a new solution for MI treatment is proposed., (© 2023. The Author(s).)

Objective: To explore the genetic basis for a sib pair featuring 17beta-hydroxysteroid dehydrogenase type 3 deficiency., Methods: Genomic DNA was extracted from the proband, her sister, and their parents, and was subjected to sequencing analysis with a gene panel for sexual development. Suspected variant was verified by Sanger sequencing and bioinformatic analysis., Results: Both the proband and her sister were found to harbor novel compound heterozygous missense variants of the HSD17B3 gene, namely c.839T>C (p.Leu280Pro) and c.239G>T (p.Arg80Leu), which were derived respectively from their mother and father. The variants were unreported previously and predicted to be deleterious by PolyPhen2, MutationTaster and other online software. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.839T>C(p.Leu280Pro) and c.239G>T (p.Arg80Leu) were predicted to be likely pathogenic (PM2+PP1+PP2+PP3+PP4, PM2+PM5+PP1+PP2+PP3+PP4)., Conclusion: The compound heterogeneous variants of the HSD17B3 gene probably underlay the disease in this sib pair. 17beta-hydroxysteroid dehydrogenase type 3 deficiency may lack specific clinical features and laboratory index, genetic testing can facilitate a definitive diagnosis.

Objective: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function., Methods and Material: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020., Results: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide ( D LCO ) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO . Pulmonary interstitial damage may be associated with abnormal D LCO ., Conclusion: Pulmonary function, particularly D LCO , declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO ., Competing Interests: Conflict of interest: W. Qin has nothing to disclose. Conflict of interest: S. Chen has nothing to disclose. Conflict of interest: Y. Zhang has nothing to disclose. Conflict of interest: F. Dong has nothing to disclose. Conflict of interest: Z. Zhang has nothing to disclose. Conflict of interest: B. Hu has nothing to disclose. Conflict of interest: Z. Zhu has nothing to disclose. Conflict of interest: F. Li has nothing to disclose. Conflict of interest: X. Wang has nothing to disclose. Conflict of interest: Y. Wang has nothing to disclose. Conflict of interest: K. Zhen has nothing to disclose. Conflict of interest: J. Wang has nothing to disclose. Conflict of interest: Y. Wan has nothing to disclose. Conflict of interest: H. Li has nothing to disclose. Conflict of interest: I. Elalamy has nothing to disclose. Conflict of interest: C. Li has nothing to disclose. Conflict of interest: Z. Zhai has nothing to disclose. Conflict of interest: C. Wang has nothing to disclose., (Copyright ©ERS 2021.)

Combined with the literature, recognize the clinical features and molecular genetic mechanism of the disease. 17a-hydroxylase/17,20-lyase deficiency, a rare form of congenital adrenal hyperplasia, is caused by mutations in the cytochrome P450c17 gene (CYP17A1), and characterized by hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism. We presented the clinical and biochemical characterization in two patients (a 13 year-old girl (46, XX) with hypokalemia and lack of pubertal development, a 11 year-old girl (46, XY) with female external genitalia and severe hypertension). CYP17A1 mutations were detected by PCR and direct DNA sequencing in patients and their parents. A homozygous mutation c.985&#95;987delTACinsAA (p.Y329KfsX418) in Exon 6 was found in patient 1, and a homozygous deletion mutation c.1459&#95;1467delGACTCTTTC (p.Asp487&#95;Phe489del) in exon 8 in patient 2. The patients manifested with hypertension, hypokalemia, sexual infantilism should be suspected of having 17a-hydroxylase/17,20-lyase deficiency. Definite diagnosis is depended on mutation analysis. Hydrocortisone treatment in time is crucial to prevent severe hypertension and hypokalemia.

The aim of this study was to investigate the relationship between serum 11β-HSD2 mRNA level and insulin sensitivity in term small-for-gestational age (SGA) neonates after birth. The 38 infants were divided into two groups, the SGA group and the appropriate-for-gestational age (AGA) group. The placental 11β-HSD2 mRNA abundance and concentration of cortisol, fasting glucose, fasting insulin, adiponectin, visfatin and insulin-like growth factor-I (IGF-1) in the umbilical vein plasma were measured. The results showed that in the SGA group, neonates had lower levels of placental 11β-HSD2 mRNA and serum cortisol, and higher fasting insulin and HOMA-IR compared to AGA group. For some insulin sensitivity relative factor, levels of serum adiponectin and IGF-1 were lower while visfatin was higher in the SGA group than AGA group. Correlation analyses revealed that 11β-HSD2 mRNA level had a negative correlation with fasting insulin, HOMA-IR and visfatin.