Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective:To explore the distribution characteristics and drug resistance of pathogenic bacteria in neonatal infectious diseases in Meizhou city from 2019 to 2023, and to guide the use of clinical antibacterial drugs.Methods:A retrospective analysis was conducted on the bacterial culture and drug sensitivity results of neonates with bacterial infectious diseases diagnosed and treated in Meizhou People's Hospital from January 2019 to December 2023. The distribution characteristics of pathogenic bacteria were observed, and the resistance of common pathogenic bacteria to antibacterial drugs was analyzed.Results:A total of 660 strains of pathogenic bacteria were collected, of which 434 isonates (65.76%) came from sputum, 111 isonates (16.82%) came from blood and 73 isonates (11.06%)came from umbilical secretions or other secretions.Gram-negative bacteria accounted for 55.45%(366/660), mainly Escherichia coli and Klebsiella pneumoniae. Gram-positive bacteria accounted for 42.42%(280/660), mainly Staphylococcus aureus and Streptococcus agalactiae. A total of 216 strains of multidrug-resistant bacteria were found, and the top three were extended spectrum beta-lactamases (ESBLs)-producing Escherichia coli, methicillin-resistant Staphylococcus aureus and ESBLs-producing Klebsiella pneumoniae.The resistance rates of Escherichia coli and Klebsiella pneumoniae to cefuroxime and cefotaxime were higher, and the resistance rates to ceftazidime, piperacillin-tazobactam and carbapenems were lower. The resistance rate of Staphylococcus aureus to penicillin was 91.61%. Streptococcus agalactiae was sensitive to penicillin, and both of them were sensitive to linezolid and vancomycin. Conclusions:The main pathogens of neonatal bacterial infection are Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus agalactiae. The proportion of multidrug-resistant bacteria is high, mainly producing ESBLs bacteria. Antibiotics should be rationally selected according to the distribution and drug resistance of pathogens.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

Objective To investigate the effects of taurine-upregulated gene 1(TUG1)on the biological functions of human um-bilical vein endothelial cells(HUVEC)such as apoptosis,proliferation,and migration after oxygen-glucose deprivation/reoxygenation(OGD/R)injury.Methods HUVEC were treated with OGD/R to establish a cell model injured by OGD/R.Small interfering RNA si-lencing TUG1(si-TUG1)and its negative control(si-NC)were transfected,and the cells were divided into the control group,OGD/R group,OGD/R+si-NC group,and OGD/R+si-TUG1 group.PCR was used to detect the expression level of TUG1 in HUVEC;flow cytometry was used to detect cell apoptosis;CCK-8 assay was used to detect cell proliferation;wound-healing assay was used to detect cell migration;immunofluorescence was used to detect the expression of CD31 in HUVEC;and Western blot was used to detect the expres-sion of nuclear proliferation antigen(PCNA)protein.Results The PCR results showed that the expression level of TUG1 in OGD/R group cells was significantly higher than that in the control group(P＜0.05);si-TUG1 transfection can significantly reduce the expres-sion level of TUG1 in HUVEC(P＜0.05);the apoptosis rate of HUVEC in the si-TUG1 group was significantly lower than that in the si-NC group(P＜0.05);The cell proliferation,cell migration,immunofluorescence intensity of CD31,and the expression levels of PC-NA protein in the si-TUG1 group were higher than those in the si-NC group(P＜0.05).Conclusion Inhibiting TUG1 can significant-ly reduce the apoptosis of HUVEC under OGD/R conditions,and increase the biological functions of HUVEC,such as proliferation,mi-gration,and tubular ability.

Objective To investigate the effects of taurine-upregulated gene 1(TUG1)on the biological functions of human um-bilical vein endothelial cells(HUVEC)such as apoptosis,proliferation,and migration after oxygen-glucose deprivation/reoxygenation(OGD/R)injury.Methods HUVEC were treated with OGD/R to establish a cell model injured by OGD/R.Small interfering RNA si-lencing TUG1(si-TUG1)and its negative control(si-NC)were transfected,and the cells were divided into the control group,OGD/R group,OGD/R+si-NC group,and OGD/R+si-TUG1 group.PCR was used to detect the expression level of TUG1 in HUVEC;flow cytometry was used to detect cell apoptosis;CCK-8 assay was used to detect cell proliferation;wound-healing assay was used to detect cell migration;immunofluorescence was used to detect the expression of CD31 in HUVEC;and Western blot was used to detect the expres-sion of nuclear proliferation antigen(PCNA)protein.Results The PCR results showed that the expression level of TUG1 in OGD/R group cells was significantly higher than that in the control group(P＜0.05);si-TUG1 transfection can significantly reduce the expres-sion level of TUG1 in HUVEC(P＜0.05);the apoptosis rate of HUVEC in the si-TUG1 group was significantly lower than that in the si-NC group(P＜0.05);The cell proliferation,cell migration,immunofluorescence intensity of CD31,and the expression levels of PC-NA protein in the si-TUG1 group were higher than those in the si-NC group(P＜0.05).Conclusion Inhibiting TUG1 can significant-ly reduce the apoptosis of HUVEC under OGD/R conditions,and increase the biological functions of HUVEC,such as proliferation,mi-gration,and tubular ability.

Objective:To explore the distribution characteristics and drug resistance of pathogenic bacteria in neonatal infectious diseases in Meizhou city from 2019 to 2023, and to guide the use of clinical antibacterial drugs.Methods:A retrospective analysis was conducted on the bacterial culture and drug sensitivity results of neonates with bacterial infectious diseases diagnosed and treated in Meizhou People's Hospital from January 2019 to December 2023. The distribution characteristics of pathogenic bacteria were observed, and the resistance of common pathogenic bacteria to antibacterial drugs was analyzed.Results:A total of 660 strains of pathogenic bacteria were collected, of which 434 isonates (65.76%) came from sputum, 111 isonates (16.82%) came from blood and 73 isonates (11.06%)came from umbilical secretions or other secretions.Gram-negative bacteria accounted for 55.45%(366/660), mainly Escherichia coli and Klebsiella pneumoniae. Gram-positive bacteria accounted for 42.42%(280/660), mainly Staphylococcus aureus and Streptococcus agalactiae. A total of 216 strains of multidrug-resistant bacteria were found, and the top three were extended spectrum beta-lactamases (ESBLs)-producing Escherichia coli, methicillin-resistant Staphylococcus aureus and ESBLs-producing Klebsiella pneumoniae.The resistance rates of Escherichia coli and Klebsiella pneumoniae to cefuroxime and cefotaxime were higher, and the resistance rates to ceftazidime, piperacillin-tazobactam and carbapenems were lower. The resistance rate of Staphylococcus aureus to penicillin was 91.61%. Streptococcus agalactiae was sensitive to penicillin, and both of them were sensitive to linezolid and vancomycin. Conclusions:The main pathogens of neonatal bacterial infection are Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus agalactiae. The proportion of multidrug-resistant bacteria is high, mainly producing ESBLs bacteria. Antibiotics should be rationally selected according to the distribution and drug resistance of pathogens.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.