Analysis of MTHFR C677T genotype and related factors in H-type hypertension in Tibet, China.

BACKGROUND AND AIMS: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene. METHODS AND RESULTS: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease. CONCLUSION: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease.

Senescence of endplate osteoclasts induces sensory innervation and spinal pain.

Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.

Aggregation of One-Dimensional Wires: The Case of Long Oligoynes.

We show an unexpected aggregation phenomenon of a long oligoyne (Py[16]) with 16 contiguous triple bonds and endcapped with bulky 3,5-bi(3,5-bis-tert-butylphenyl)pyridine groups. Aggregation of 1D p-conjugated oligoyne chains is rare, given the minimal p-p intermolecular interactions of the weakly polarizable polyyne chain, as well as its flexibility that works against self assembly. In dilute solutions, the reversible aggregation of Py[16] initiates at low temperature in the range of 140-180 K, and is not observed for shorter oligoynes in this series. Cryogenic UV-Vis electronic absorption spectra and vibrational Raman spectra with different laser wavelength lines tuning from in-resonance to off-resonance conditions have been used to extract the vibrational features characterizing the Monomer and aggregate species. Theoretical calculations complement the spectroscopic findings.

A Cautionary Tale: Undetected H-type Tracheoesophageal Fistula in an Adolescent Male.

An H-type tracheoesophageal fistula is a rare congenital anomaly consisting of an abnormal passageway between the esophagus and the trachea without the presence of esophageal atresia. This condition is usually detected early in infancy; however, some patients may receive a delayed diagnosis. Symptoms experienced by people affected with an H-type tracheoesophageal fistula vary greatly and may consist of bouts of coughing when swallowing liquids and recurring lower respiratory infections. The most commonly used initial diagnostic tests can produce falsely negative results. The treatment of choice for the majority of H-type tracheoesophageal fistulas is an open surgical procedure; however, the thoracoscopic approach has proven effective in cases where the fistula is located below the thoracic outlet. In this case report, we describe a patient whose diagnosis of H-type tracheoesophageal fistula was delayed by 13 years and who was successfully treated using thoracoscopic surgery.

Targeting endothelial PDGFR-ß facilitates angiogenesis-associated bone formation through the PAK1/NICD axis.

The intricate orchestration of osteoporosis (OP) pathogenesis remains elusive. Mounting evidence suggests that angiogenesis-driven osteogenesis serves as a crucial foundation for maintaining bone homeostasis. This study aimed to explore the potential of the endothelial platelet-derived growth factor receptor-ß (PDGFR-ß) in mitigating bone loss through its facilitation of H-type vessel formation. Our findings demonstrate that the expression level of endothelial PDGFR-ß is reduced in samples obtained from individuals suffering from OP, as well as in ovariectomy mice. Depletion of PDGFR-ß in endothelial cells ameliorates angiogenesis-mediated bone formation in mice. The regulatory influence of endothelial PDGFR-ß on H-type vessels is mediated through the PDGFRß-P21-activated kinase 1-Notch1 intracellular domain signaling cascade. In particular, the endothelium-specific enhancement of PDGFR-ß facilitates H-type vessels and their associated bone formation in OP. Hence, the strategic targeting of endothelial PDGFR-ß emerges as a promising therapeutic approach for the management of OP in the near future.

[Medication rules of Chinese herbs in treatment of H-type hypertension based on data mining].

Based on the R language data mining technology, the medication rules of traditional Chinese medicine(TCM) in the treatment of H-type hypertension were discussed, and the basis and new ideas for the treatment of H-type hypertension with TCM were provided. CNKI, Wanfang, VIP, and SinoMed were searched to collect clinical studies on the treatment of H-type hypertension with TCM. The data were screened, and Excel was used to build a database. Rstudio was used to carry out drug efficacy classification, four Qi and five flavors, meridian homing, frequency of use, correlation, association rules, and clustering analyses of drugs and explore the medication rules of TCM. 191 TCM prescriptions were obtained, and the main syndromes were phlegm-dampness accumulation syndrome, phlegm and blood stasis syndrome, and Yin deficiency and Yang hyperactivity syndrome. A total of 169 kinds of TCM were used, and the frequency was 1 875 times. Among them, the drugs whose single use frequency was more than 20 times were high-frequency medicines, 26 kinds in total. They were Gestrodiae Rhizoma, Poria, Pinelliae Rhizoma, Achyranthis Bidenthis Radix, Glycyrrhizae Radix et Rhizoma, etc. The efficacy of high-frequency medicines was mainly classified as tonic medicines, blood-activating and stasis-removing medicines, liver-relieving wind medicines, and damp-clearing medicines. The four Qi of the drug were mainly warm and flat, and the five flavors were mainly sweet and bitter. The liver meridian and spleen meridian were the main meridians. The association rule analysis obtained a total of 14 groups of commonly used drug combinations, and the correlation analysis obtained 20 drug combinations with a high correlation coefficient. A total of six drug combinations were obtained by cluster analysis. Eight groups of drug pairs were obtained by association rule analysis on H-type hypertension with phlegm-dampness accumulation syndrome. Seven drug combinations with high correlation coefficients were obtained by correlation analysis, and three drug prescriptions were obtained by cluster analysis. The pathological factors of H-type hypertension are mainly phlegm, stasis, and deficiency. The disease site is in the liver, involving the spleen, lungs, and other viscera. The commonly used drugs are Gestrodiae Rhizoma, Poria, Pinelliae Rhizoma, Achyranthis Bidenthis Radix, etc. Banxia Baizhu Tianma Decoction, Tianma Gouteng Decoction, and Buyang Huanwu Decoction are commonly used prescriptions. The medication rules shown in this study can provide certain ideas for the clinical treatment of H-type hypertension with TCM.

Impact of Condition Variations on Bioelectrochemical System Performance: An Experimental Investigation of Sulfamethoxazole Degradation.

Bioelectrochemical systems (BESs) are an innovative technology for the efficient degradation of antibiotics. Shewanella oneidensis (S. oneidensis) MR-1 plays a pivotal role in degrading sulfamethoxazole (SMX) in BESs. Our study investigated the effect of BES conditions on SMX degradation, focusing on microbial activity. The results revealed that BESs operating with a 0.05 M electrolyte concentration and 2 mA/cm2 current density outperformed electrolysis cells (ECs). Additionally, higher electrolyte concentrations and elevated current density reduced SMX degradation efficiency. The presence of nutrients had minimal effect on the growth of S. oneidensis MR-1 in BESs; it indicates that S. oneidensis MR-1 can degrade SMX without nutrients in a short period of time. We also highlighted the significance of mass transfer between the cathode and anode. Limiting mass transfer at a 10 cm electrode distance enhanced S. oneidensis MR-1 activity and BES performance. In summary, this study reveals the complex interaction of factors affecting the efficiency of BES degradation of antibiotics and provides support for environmental pollution control.

Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review.

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.

Double hydrogen bonding-induced compact H-type π-π stacking enhancing rapid carrier transfer in perylene diimide supramolecules achieving high oxygen evolution performance.

Perylene diimides (PDI) are widely used in photocatalytic oxygen evolution due to their deep valence band potentials. Here, we report the synthesis of a unique supramolecular photocatalyst (designated s-PDI-P1) by introducing hydroxyl and carboxyl groups at the imide position of PDI. This modification allows the formation of intermolecular double hydrogen bond structures between the hydroxyl groups, oxygen atoms on the perylene cores and the carboxyl groups. The resulting double hydrogen bonding structures reduce lateral slip and promote the formation of supramolecular structures with H-type π-π stacking. In addition, the intermolecular hydrogen bonding interactions between the hydroxyl groups and the oxygen atoms on the perylene cores bring the PDI molecules closer together, enhancing the conjugation of the PDI supramolecules and facilitating the formation of ultrathin nanosheet-like structures. In this study, we successfully constructed ultrathin nanosheets of the supramolecular photocatalyst s-PDI-P1 with a compact H-type π-π stacking structure, which exhibited enhanced charge transfer capability, shorter charge migration distance, and achieved a high photocatalytic oxygen evolution rate of 3.23 mmolg-1h-1. These results highlight the potential of intermolecular double hydrogen bond structures to improve the separation and migration driving force of photogenerated charges, thus providing a novel design strategy for organic photocatalysts.

Diagnosis and Management of Congenital H-Type Tracheoesophageal Fistula: Results of a National Survey.

BACKGROUND: Congenital h-type tracheoesophageal fistula (H-TEF) without esophageal atresia (EA) represents about 4% of congenital esophageal anomalies. The diagnosis is challenging, and surgery is considered curative. The aim was to report a national survey on the diagnosis, management, and outcome of patients with congenital H-TEF. METHODS: Following approval of the Italian Society of Pediatric Surgery, a survey was sent to all Pediatric Surgery Units to retrospectively collect H-TEF treated in the period 2010-2022. Descriptive analysis was performed, and results are given as prevalence, mean ± standard deviation (SD), or median and interquartile range (IQR). RESULTS: The survey was sent to 65 units. Seventeen responded with one or more cases; 78 patients were diagnosed with H-TEF during the study period. Associated malformations were present in 43%, mostly cardiac (31%). The most frequent symptoms were cough (36%), bronchopneumonia (24%), and dysphagia (19%). H-TEF was detected by tracheobronchoscopy (90%), and/or upper GI (58%), and/or esophagoscopy (32%). The median age at diagnosis was 23 days (1 day-18 years). The most common approach was cervicotomy (76%), followed by thoracoscopy (14%) and thoracotomy (9%). The fistula underwent ligation and section of the fistula in 90% of the patients and clip closure and section in 9%. In one patient, the fistula was cauterized endoscopically. H-TEF preoperative cannulation was performed in 68% of cases, and a drain was placed in 26%. One month after surgery, 13% of the patients had mild persisting symptoms, mainly hypophonia. Recurrence occurred in 5%, and a second recurrence occurred in 1%. CONCLUSIONS: H-TEF prevalence was six cases/year, consistent with the expected rate of five cases/year in our country. The diagnosis was challenging, sometimes delayed, and, in most patients, required multiple examinations. Fistula ligation and section through cervicotomy were the most frequent treatment. Long-term outcomes are good, and recurrence is a rare event.

Double Cystic Ducts Encountered During Laparoscopic Cholecystectomy in a Male Patient With Cholelithiasis: A Case Report.

One of the most uncommon cystic duct abnormalities is double cystic ducts exiting a single gallbladder. Adequate knowledge of this anomaly should be kept in mind to avoid any surgical complications. We present a case of a 49-year-old Asian Pakistani male patient who had an elective laparoscopic cholecystectomy and was discovered to have two distinct cystic ducts leaving the gallbladder. On examination, there were no other clinically relevant signs except for mild tenderness in the right hypochondrium. Ultrasound of the abdomen and pelvis confirmed the diagnosis of cholelithiasis. Standard four-port laparoscopic cholecystectomy was done via the open Hasson technique under general anesthesia. After meticulous dissection of the Calot's triangle, double cystic ducts were discovered draining a single gallbladder. The gallbladder was retrieved after clipping and cutting the cystic ducts and cystic artery. To minimize the risk of complications, surgeons must be aware of the numerous anatomical variations that may exist.

The effect of nitrogen source and levels on hybrid aspen tree physiology and wood formation.

Nitrogen can be taken up by trees in the form of nitrate, ammonium and amino acids, but the influence of the different forms on tree growth and development is poorly understood in angiosperm species like Populus. We studied the effects of both organic and inorganic forms of nitrogen on growth and wood formation of hybrid aspen trees in experimental conditions that allowed growth under four distinct steady-state nitrogen levels. Increased nitrogen availability had a positive influence on biomass accumulation and the radial dimensions of both xylem vessels and fibers, and a negative influence on wood density. An optimal level of nitrogen availability was identified where increases in biomass accumulation outweighed decreases in wood density. None of these responses depended on the source of nitrogen except for shoot biomass accumulation, which was stimulated more by treatments complemented with nitrate than by ammonium alone or the organic source arginine. The most striking difference between the nitrogen sources was the effect on lignin composition, whereby the abundance of H-type lignin increased only in the presence of nitrate. The differential effect of nitrate is possibly related to the well-known role of nitrate as a signaling compound. RNA-sequencing revealed that while the lignin-biosynthetic genes did not significantly (FDR <0.01) respond to added NO3 - , the expression of several laccases, catalysing lignin polymerization, was dependent on N-availability. These results reveal a unique role of nitrate in wood formation and contribute to the knowledge basis for decision-making in utilizing hybrid aspen as a bioresource.

Ineffective ventilation in a very low birth weight infant with H-type Tracheoesophageal Fistula with bilateral chemical pneumonitis. A lesson learned.

Tracheoesophageal fistula (TEF) with or without associated esophageal atresia (EA) in the neonate is challenging to diagnose and manage its complications like aspiration, respiratory distress, and other associated anomalies. To stabilize, ventilate and prepare for surgical correction, understanding the H-nature of disease and anticipation of problems and their management will improve survival. We present a newborn with tracheoesophageal fistula without atresia from resource-limited settings and lessons we learned from the case.

LOX-1 regulation of H-type vascular endothelial cell regeneration in hyperglycemia.

AIMS: Diabetic osteoporosis (DOP) is the most common secondary form of osteoporosis. Diabetes mellitus affects bone metabolism; however, the underlying pathophysiological mechanisms remain unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression is upregulated in conditions characterized by vascular injury, such as atherosclerosis, hypertension, and diabetes. Additionally, Notch, HIF-1α, and VEGF are involved in angiogenesis and bone formation. Therefore, we aimed to investigate the expression of Notch, HIF-1α, and VEGF in the LOX-1 silencing state. METHODS: Rat bone H-type vascular endothelial cells (THVECs) were isolated and cultured in vitro. Cell identification was performed using immunofluorescent co-expression of CD31 and Emcn. Lentiviral silencing vector (LV-LOX-1) targeting LOX-1 was constructed using genetic recombination technology and transfected into the cells. The experimental groups included the following: NC group, HG group, LV-LOX-1 group, LV-CON group, HG + LV-LOX-1 group, HG + LV-CON group, HG + LV-LOX-1 + FLI-06 group, HG + LV-CON + FLI-06 group, HG + LV-LOX-1 + LW6 group, and HG + LV-CON + LW6 group. The levels of LOX-1, Notch, Hif-1α, and VEGF were detected using PCR and WB techniques to investigate whether the expression of LOX-1 under high glucose conditions has a regulatory effect on downstream molecules at the gene and protein levels, as well as the specific molecular mechanisms involved. RESULTS: High glucose (HG) conditions led to a significant increase in LOX-1 expression, leading to inhibition of angiogenesis, whereas silencing LOX-1 can reverse this phenomenon. Further analysis reveals that changes in LOX-1 will promote changes in Notch/HIF-1α and VEGF. Moreover, Notch mediates the activation of HIF-1α and VEGF. CONCLUSIONS: The activation of LOX-1 and the inhibition of Notch/HIF-1α/VEGF in THVECs are the main causes of DOP. These findings contribute to our understanding of the pathogenesis of DOP and offer a novel approach for preventing and treating osteoporosis.

Solvent Geometry Regulated J- and H-Type Aggregates of Photoswitchable Organogelator: Phase-Selective Thixotropic Gelation and Oil Spill Recovery.

We demonstrate supramolecular polymerization and formation of 1D nanofiber of azobenzene based organogelator (AZO-4) in cyclic hydrocarbon solvents (toluene and methylcyclohexane). The AZO-4 exhibits J- and H-type aggregates in toluene: MCH (9 : 1) and MCH: toluene (9 : 1) respectively. The type of aggregate was governed by the geometry of the solvents used in the self-assembly process. The J-type aggregates with high thermal stability in toluene is due to the enhanced interaction of AZO-4 π- surface with the toluene π-surface, whereas H-aggregate with moderate thermal stability in MCH was due to the interruption of the cyclic hydrocarbon in van der Waals interactions of peripheral chains of AZO-4 molecule. The light induced reversible photoisomerization is observed for both J- and H-aggregates. The macroscopic property revealed spontaneous and strong gelation in toluene preferably due to the strong interactions of the AZO-4 nanofibers with the toluene solvent molecules compared to the MCH. The rheological measurements revealed thixotropic nature of the gels by step-strain experiments at room temperature. The thermodynamic parameter (ΔHm) of gel-to-sol transition was determined for all the gels to get more insight into the gelation property. Furthermore, the phase selective gelation property was extended to the oil spill recovery application using diesel/water and petrol/water mixture.

Relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and neutrophil gelatinase-associated lipocalin in early renal injury in H-type hypertension.

OBJECTIVE: To analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury. METHOD: A total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was < 10 µmol/L they were assigned to the non-H-type hypertensive group. Blood lipid indexes, renal function indexes and blood glucose indexes were collected, and the differences between the two groups were compared. Furthermore, MTHFR C677T genotype distribution and allele frequency and Hcy level of MTHFR C677T genotype were compared, and logistic multiple regression analysis was conducted for the correlation of different genotypes of MTHFR C677T and the early kidney injury marker NGAL. RESULTS: In the non-H-type hypertensive group, the levels of Hcy and NGAL, cystatin, blood urea nitrogen, serum creatinine, uric acid, serum ß2-microglobulin and urinary microalbumin-to-creatinine ratio increased significantly, and the glomerular filtration rate level decreased significantly, when compared with the H-type hypertensive group, with statistical differences (p < 0.05). The H-type hypertensive group and the non-H-type hypertensive group had significant differences in the CC, CT and TT genotypes and allele frequencies at the MTHFR C677T locus. The MTHFR C677T gene mutation rate of the H-type hypertensive group was significantly higher than that of the non-H-type hypertensive group. The H-type hypertensive group had higher levels of the TT genotype and CT genotype Hcy. There was a statistical difference (p < 0.05). CONCLUSION: Methylenetetrahydrofolate reductase C677T polymorphism is correlated with the Hcy level, and its gene polymorphism will affect the Hcy level. Methylenetetrahydrofolate reductase C677T polymorphism has an interactive effect with NGAL. Screening NGAL and reducing Hcy levels are valuable methods for the prevention and treatment of early renal injury in patients with H-type hypertension and help improve the prognosis of patients and their quality of life.

Relationship between TyG index and the degree of coronary artery lesions in patients with H-type hypertension.

BACKGROUND: The TyG index, a prominent metric for assessing insulin resistance, has gained traction as a prognostic tool for cardiovascular disease. Nevertheless, the understanding of the prognostic significance of the extent of coronary artery stenosis in individuals afflicted with H-type hypertension remains limited. METHODS: A retrospective study was conducted at Wuhan Third Hospital, including a cohort of 320 inpatients who were diagnosed with hypertension in combination with coronary artery disease. The study period spanned from January 1, 2021, to February 1, 2023. The study cohort was stratified based on the severity of stenosis into three distinct groups: low stenosis, medium stenosis, and high stenosis, as determined by the Gensini score derived from coronary angiography findings. The present study aimed to investigate the association between the severity of coronary stenosis and the number of lesion branches, utilizing the TyG index as a testing indicator. The predictive ability of TyG for coronary lesion severity was assessed using logistic regression analysis. RESULTS: The results of our study indicate a positive correlation between elevated levels of TyG and an increased susceptibility to severe stenosis in individuals diagnosed with H-type hypertension. Upon careful consideration of potential confounding variables, it has been observed that the TyG index exhibits a robust association with the likelihood of severe stenosis in individuals with H-type hypertension (odds ratio [OR] = 4000, 95% confidence interval CI 2.411-6.635, p = 0.0001), as well as the prevalence of multivessel disease (OR = 1.862, 95% CI 1.036-3.348, p < 0.0001). The TyG index demonstrated superior predictive ability for severe coronary stenosis in patients with H-type hypertension compared to those without H-type hypertension (area under the curve [AUC] = 0.888, 95% confidence interval CI 0.838-0.939, p < 0.0001, versus AUC = 0.615, 95% CI 0.494-0.737, p < 0.05). CONCLUSION: The TyG index is an independent risk factor for the degree of coronary stenosis and a better predictor in patients with H-type hypertension combined with coronary artery disease.

Homocysteine, hyperhomocysteinemia and H-type hypertension.

Homocysteine (Hcy) is a sulfur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6 and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 µmol/L or 15 µmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH.

Lewis a-b- histo-blood group antigen phenotype is predictive of severe COVID-19 in the black South African population group.

Several risk factors have been associated with SARS-CoV-2 infections and severity of COVID-19 disease it causes. This study investigated whether variations in histo-blood group antigen (HBGA) expression can predispose individuals to SARS-CoV-2 infections and severity of the disease. Nasopharyngeal swabs, randomly selected from SARS-CoV-2 positive and SARS-CoV-2 negative individuals, were tested for Lewis and H-type 1 HBGA phenotypes by ELISA using monoclonal antibodies specific to Lewis a, Lewis b and H type 1 antigens. The most common Lewis HBGA phenotype among all study participants was Lewis a-b+ (46%), followed by Lewis a-b- (24%), Lewis a+b- and Lewis a+b+ (15% each), while 55% of the study participants were H-type 1. Although SARS-CoV-2 negative individuals had a lower likelihood of having a Lewis a-b- phenotype compared to their SARS-CoV-2 positives counterparts (OR: 0.53, 95% C.I: 0.255-1.113), it did not reach statistical significance (P = 0.055). The frequency of Lewis a+b+, Lewis a+B-, Lewis a-b+, H type 1 positive and H type 1 negative were consistent between SARS-CoV-2 positive and SARS-CoV-2 negative individuals. When stratified according to severity of the disease, individuals with Lewis a+b- phenotype had a higher likelihood of developing mild COVID-19 symptoms (OR: 3.27, 95% CI; 0.9604-11.1), but was not statistically significant (P = 0.055), while Lewis a-b- phenotype was predictive of severe COVID-19 symptoms (OR: 4.3, 95% CI: 1.274-14.81), P = 0.016. In conclusion, individuals with Lewis a-b- phenotype were less likely to be infected by SARS-CoV-2, but when infected, they were at risk of severe COVID-19.

DLL4/Notch blockade disrupts mandibular advancement-induced condylar osteogenesis by inhibiting H-type angiogenesis.

BACKGROUND: Blocking Delta-like 4 (DLL4)/Notch has emerged as a promising therapeutic target for the treatment of tumours by deregulating angiogenesis. However, DLL4/Notch serves as a negative regulator of angiogenesis in multiple organs while acting as a positive regulator of H-type angiogenesis in postnatal long bones. Therefore, the effect of DLL4/Notch signalling blockade on mandibular condylar osteogenesis attracted our attention. OBJECTIVE: To explore the effect of blocking DLL4/Notch on mandibular advancement (MA)-induced condylar osteogenesis. METHODS: Six-week-old young male C57BL/6J mice (n = 40) were randomly divided into four groups: control group, MA group, MA + Anti-DLL4 group and MA + IgG group. Of note, IgG served as the isotype control for the anti-DLL4. The femurs, tibias and mandibular condyles were collected after sacrificing mice on Day 31 for morphology, micro-computed tomography, immunofluorescence, histology and immunohistochemistry evaluation. RESULTS: First, DLL4/Notch blockade shortened femoral length and reduced bone mass by inhibiting H-type angiogenesis. Second, DLL4/Notch blockade disrupted MA-induced condylar head volume and quality by inhibiting H-type angiogenesis. Mechanistically, blocking DLL4/Notch reduced the number of runt-related transcription factor 2+ (RUNX2+ ) early osteoprogenitors and the expression of Noggin protein in the condylar subchondral bone by inhibiting H-type angiogenesis. In addition, blockade of DLL4/Notch also destroyed the condylar cartilage layer. CONCLUSION: DLL4/Notch blockade results in shortened femurs and osteopenia, as well as impaired MA-induced condylar osteogenic volume and quality in growing mice by inhibiting H-type angiogenesis. Therefore, when blocking DLL4/Notch is used as a treatment target for diseases, attention should be paid to its impact on the bone mass of mandibular condyle.