ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

Objective To investigate the levels and influencing factors for eye lens dose of interventional radiology workers, and to provide a basis for reasonable and scientific radiation protection. Methods Thermoluminescent eye lens dosimeters were used to monitor the left and right eye lens doses of interventional radiology workers in real time during different surgical positions and varying eye protection conditions. The annual eye lens doses for the operators were estimated based on their yearly workload. The differences in eye lens doses under different conditions were analyzed and the influencing factors were identified. Results For individual interventional operations, the range of personal dose equivalent H_p(3) of the left eye of interventional radiology workers was ( < MDL ~ 418.33) μSv, the median (Q₁, Q₃) was 9.29 ( < MDL, 40.79) μSv, and the mean was 40.79 ± 70.36 μSv. The estimated annual eye lens doses were 4.05 mSv and 17.80 mSv based on the median and mean values of the eye lens dose of a single operation multiplied by average annual frequency of operations per person, respectively. The left eye lens dose was higher than the right eye lens dose of the same operator (Z = −4.24, P < 0.05), and the dose of the right eye lens was strongly positively correlated with that of the left eye lens. The left eye lens dose of the first surgeon was higher than that of the second surgeon in the same operation (Z = −3.10, P < 0.05). The eye lens dose was influenced by operator position (χ² = 9.149, P = 0.002, OR = 8.343), eye protection (χ² = 4.619, P = 0.032, OR = 4.352), and air kerma area product (χ² = 8.032, P = 0.005, OR = 5.488). Conclusion According to the results of this study, a significant portion of interventional operators have eye lens doses that approach or exceed international occupational dose limits. It is recommended to pay attention to the operation frequency of the first operator and the air kerma area product of interventional operation, and strengthen radiation protection and dose monitoring for the eye lens of interventional radiology workers.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing＜3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was＜20％.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To standardize the origin of Rubi Fructus by using ITS2 and matK molecular markers to identify Rubi Fructus and its analogues. Methods:The ITS and matK sequences of Rubus chingii Hu, Rubus corchorifolius L.f., Rubus hirsutus Thunb., Rubus parvifolius L., Rubus buergeri Miq. and Rubus lambertianus Ser. were amplified and sequenced. The hidden Markov model was used to remove 5.8S and 28S from ITS sequences. A total of 25 ITS2 sequences were obtained. And a total of 22 matK sequences were obtained by proofreading by Glustal software. MEGA software was used for matK and ITS2 sequences analysis, intraspecific and interspecific genetic distances caculation, and neighbor joining (NJ) phylogenetic tree construction. ITS2 secondary structure was predicted by ITS2 database and aligned by 4Sale software. Profile neighbor-joining (PNJ) phylogenetic tree was constructed based on combined ITS2 sequence and its secondary structure by ProfDistS software. Results:An obvious barcoding gap between Rubi Fructus and its analogues was showed. The topological relationship between NJ tree and PNJ tree was consistent, and each taxon exhibits monophyly. The ITS2 secondary structure of Rubi Fructus was significant different from its analogues.Conclusions:It is recommended that both ITS2 and matK markers can serve as DNA barcodes for identifying Rubi Fructus and its analogues. The addition of ITS2 secondary structure information can enrich the identification results and provide theoretical support for resource research and variety selection of Rubi Fructus.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

BACKGROUND:The repair process of skin trauma is complex and susceptible to infection,easy to lead to poor healing,is the current difficulty and hot spot in wound repair research,and has received extensive attention in the fields of traditional Chinese medicine and tissue engineering. OBJECTIVE:To investigate the effect of moxibustion and reduced graphene oxide/cerium oxide nanocomposite on promoting the healing of infectious wounds. METHODS:(1)Reduced graphene oxide/cerium dioxide nanocomposites with mass ratios of 2:1,1:1 and 1:2 were synthesized by hydrothermal method.The resulting composites were recorded as G2C1,G1C1 and G1C2,respectively.The photothermal properties,cytotoxicity and antibacterial properties of the three kinds of materials were tested.After taking moxa sticks,three kinds of moxibustion distances were set(3.0-3.5 cm,recorded as moxibustion 1;2.5-3.0 cm,recorded as moxibustion 2;2.0-2.5 cm,recorded as moxibustion 3).Moxibustion was applied to the surface of human skin for 10 minutes to detect the photothermal properties.The antibacterial properties of moxibustion were tested at three different distance intervals.Simultaneously,the back body surface infrared imaging of rats with different mass concentrations of G1C1 material,moxibustion(three kinds of moxibustion distances)and moxibustion 2+G1C1 material was detected.(2)Sixty male Sprague-Dawley rats were selected to model the wound of Staphylococcus aureus infection.48 hours later,they were randomly divided into 10 groups with 6 rats in each group:control group(did not receive any treatment),mupirocin group,moxibustion 2+G1C1 group,moxibustion 1 group,moxibustion 2 group,moxibustion 3 group and 60,80,100,and 120 μg/mL G1C1 groups(The G1C1 group was given 808 nm near-infrared laser irradiation for 10 min/time,and the G1C1 suspension was loaded on the wound surface before each treatment.Each group of moxibustion underwent in-situ suspension moxibustion,and the intervention time was 10 min/time.Moxibustion 2+G1C1 group was loaded with G1C1 suspension on the wound surface before each treatment,and moxibustion was suspended in situ with moxa strips,and the intervention time was 10 min/time).The frequency of treatment was 2 days once.Wound healing,wound colony count and repair were detected after 7 days of intervention. RESULTS AND CONCLUSION:(1)The three kinds of reduced graphene oxide/cerium dioxide nanocomposites had good photothermal properties,and the higher the mass concentration of the composites,the better the photothermal properties.The temperature of the moxibustion 2 group reached 47.6 ℃for 10 minutes without causing thermal damage,which was more suitable for animal experiments.The results of co-culture with NIH-3T3 cells exhibited that 60,80,and 100 μg/mL G1C1 had good biocompatibility.The results of a co-culture experiment with Staphylococcus aureus suspension displayed that G2C1,G1C1 and G1C2 had good antibacterial activity,among which G1C1 group demonstrated excellent antibacterial performance,and the antibacterial rate reached 100％when its mass concentration was 80 μg/mL.60-120 μg/mL G1C1 could effectively remove Staphylococcus aureus biofilm,and the higher the material mass concentration,the better the removal effect.Moxibustion could also effectively remove Staphylococcus aureus biofilm,and the closer the moxibustion was,the better the removal effect.(2)Compared with the control group,the wound area of the mupirocin group,moxibustion 2 group,moxibustion 2+G1C1 group and 80,100 μg/mL G1C1 groups was significantly reduced on day 7 of treatment,and the quality of wound repair was better.Mupirocin,G1C1,moxibustion and moxibustion 2+G1C1 could effectively remove the residual bacteria on the wound surface,and the higher the mass concentration of G1C1,the lower the residual bacteria.Among them,the wound repair efficiency and bacterial residue of 80 μg/mL G1C1 group and moxibustion 2 group were very similar,and the wound repair efficiency of both was better than that of mupirocin group.In addition,it was also observed that the combination of materials and moxibustion had a better ability to clear wound bacteria than that used alone.(3)The results confirm that moxibustion,reduced graphene oxide/cerium dioxide nanocomposites and their combination have good anti-infection and wound healing effects.