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ObjectiveTo observe the effects of Youguiwan on bone metabolism and bone morphogenetic protein-2 （BMP-2）/Smad signaling pathway in ovaries-removed rats with osteoporosis and study the mechanism of Youguiwan in the prevention and treatment of osteoporosis. MethodA postmenopausal rat model of osteoporosis was prepared by bilateral ovariectomy. The 40 female SD rats were randomly divided into five groups， including sham operation group， model group， alendronate sodium group （0.1 mg·kg-1）， and high-dose and low-dose （5.36 and 2.68 g·kg-1） groups of Youguiwan. The drug was given seven days after modeling， once a day for 12 weeks. After the treatment， the changes in femur tissue structure were observed by micro-CT， including bone mineral density （BMD）， bone volume/total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， bone surface/bone volume （BS/BV）， and trabecular separation （Tb.Sp）. Ossification was observed by saffrane-solid green staining， and serum levels of bone metabolism markers， including bone alkaline phosphatase （BALP）， osteocalcin （BGP）， type Ⅰ procollagen amino terminal propeptide （PINP）， and tartrate-resistant acid phosphatase 5b （TRACP-5b）， were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of Runx2， BMP-2， and Smad1 in rat femur were detected by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham operation group， bone trabecula in the model group was sparse. BMD， BV/TV， Tb.N， and Tb.Th were decreased （P<0.05， P<0.01）. BS/BV （P<0.05） and Tb.Sp were increased. The content of BGP， BALP， PINP， and TRACP-5b in serum was significantly increased （P<0.01）. The mRNA and protein expressions of Runx2， BMP-2， and Smad1 in rat femur were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the number of bone trabeculae in the high-dose and low-dose groups of Youguiwan was increased， and the bone microstructure was improved. BMD， BV/TV， Tb.N， and Tb.Th were increased significantly （P<0.05， P<0.01）， and BS/BV and Tb.Sp were increased. The content of bone metabolic markers decreased （P<0.05， P<0.01）. ConclusionYouguiwan has certain preventive and therapeutic effects on postmenopausal osteoporosis， and its mechanism may be related to promoting bone formation by regulating the BMP-2/Smad signaling pathway.
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Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.
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Objective:To compare the effects of pressure controlled ventilation (PCV) and volume controlled ventilation (VCV) on respiratory mechanics, hemodynamics and biochemical metabolism in patients undergoing laparoscopic colorectal cancer surgery.Methods:The clinical data of 78 patients underwent laparoscopic colorectal cancer surgery from August 2019 to June 2020 in Inner Mongolia People′s Hospital were retrospectively analyzed. Among them, 39 patients were treated with PCV (PCV group), and 39 were treated with VCV (VCV group). The respiratory mechanics, hemodynamics and biochemical metabolism indexes 10 min after anesthesia induction (T 1), 10 min after pneumoperitoneum + low head and foot height (T 2), 60 min after pneumoperitoneum + low head and foot height (T 3) and 120 min after pneumoperitoneum + low head and foot height (T 4) were recorded. The respiratory mechanical indexes included mean airway pressure (P mean), airway peak pressure (P peak), pressure of end tidal carbon dioxide (P ETCO 2) and dynamic lung compliance (C Ldyn); hemodynamic indexes included mean arterial pressure (MAP) and heart rate; and biochemical metabolic indexes included base excess, serum natrium, serum potassium, negative logarithm of the hydrogen ion concentration (pH) and blood glucose. Results:The P mean, P peak and P ETCO 2 T 1 to T 4 in PCV group were significantly lower than those in VCV group, P mean: (7.12 ± 1.37) cmH 2O (1 cmH 2O = 0.098 kPa) vs. (8.54 ± 1.84) cmH 2O, (9.80 ± 2.26) cmH 2O vs. (11.63 ± 2.87) cmH 2O, (9.51 ± 2.17) cmH 2O vs. (11.72 ± 2.90) cmH 2O, (7.04 ± 1.34) cmH 2O vs. (8.65 ± 1.88) cmH 2O; P peak: (13.41 ± 2.68) cmH 2O vs. (15.06 ± 3.05) cmH 2O, (20.92 ± 3.11) cmH 2O vs. (23.45 ± 4.02) cmH 2O, (21.14 ± 3.50) cmH 2O vs. (23.69 ± 4.26) cmH 2O, (15.03 ± 2.74) cmH 2O vs. (16.45 ± 3.21) cmH 2O; P ETCO 2: (30.59 ± 1.57) mmHg (1 mmHg = 0.133 kPa) vs. (32.04 ± 2.11) mmHg, (35.02 ± 4.15) mmHg vs. (39.88 ± 4.76) mmHg, (35.90 ± 4.22) mmHg vs. (40.11 ± 4.87) mmHg, (34.33 ± 4.17) mmHg vs. (37.65 ± 2.69) mmHg; the C Ldyn was significantly higher than that in VCV group: (40.68 ± 3.98) ml/cmH 2O vs. (35.47 ± 2.56) ml/cmH 2O, (30.25 ± 3.21) ml/cmH 2O vs. (22.40 ± 2.75) ml/cmH 2O, (29.78 ± 3.06) ml/cmH 2O vs. (22.60 ± 2.81) ml/cmH 2O, (40.32 ± 4.25) ml/cmH 2O vs. (33.61 ± 2.81) ml/cmH 2O, and there were statistical differences ( P<0.01 or <0.05). The MAP and heart rate T 1 to T 4 in PCV group were significantly lower than those in VCV group, and there was statistical difference ( P<0.01 or <0.05). The base excess, serum natrium, serum potassium and pH T 1 to T 4 in PCV group were significantly higher than those in VCV group, while the blood glucose was significantly lower than that in VCV group, and there was statistical difference ( P<0.01 or <0.05). Conclusions:Compared with VCV, PCV can promote the recovery of respiratory mechanics index, stabilize hemodynamics and improve biochemical metabolism index in patients undergoing laparoscopic colorectal cancer surgery.
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Objective:To analyze and compare the corneal higher order aberration (HOA) after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).Methods:A non-randomized controlled study was conducted.Sixty myopic patients (60 eyes) who underwent FS-LASIK or SMILE correction at Shandong Eye Hospital from April 2018 to January 2020 were enrolled and the data from the right eye were collected for analysis.Thirty cases (30 eyes) who received FS-LASIK in FS-LASIK group and 30 cases (30 eyes) who received SMILE in SMILE group had a preoperative equivalent spherical diopter of (-5.36±1.11)D and (-4.93±1.03)D, respectively.The HOA of the 6-mm anterior surface, posterior surface, and whole cornea were measured before surgery and at 1, 3, 6, and 12 months after surgery using Pentacam.The root mean square values (μm) of total corneal HOA, spherical aberration, coma and trefoil were obtained.Differences in the above root mean square values at different time points were compared between the two groups.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Shandong Eye Hospital (No.SDSYKYY20180306). Written informed consent was obtained from each subject.Results:The preoperative and 1-, 3-, 6-, 12-month postoperative total HOA of the anterior corneal surface were (0.428±0.126), (0.775±0.169), (0.811±0.194), (0.759±0.214), (0.704±0.199)μm in the FS-LASIK group and (0.409±0.094), (0.656±0.148), (0.681±0.161), (0.668±0.175), (0.648±0.160)μm in the SMILE group, with a significant overall difference ( Fgroup=5.652, P=0.024; Ftime=107.169, P<0.01). Compared with SMILE group, the postoperative total HOA of anterior corneal surface and spherical aberration at different time points were increased in FS-LASIK group, showing statistically significant differences (all at P<0.05). Compared with before surgery, the postoperative total HOA of the anterior corneal surface and spherical aberration at different time points were increased in both groups, showing statistically significant differences (all at P<0.05). In the two groups, the 6- and 12-month postoperative total HOA of the anterior corneal surface were reduced in comparison with the 3-month postoperative ones of the anterior corneal surface, and the 12-month postoperative spherical aberrations of the anterior corneal surface were significantly reduced in comparison with the 1- and 3-month postoperative ones of the anterior corneal surface, showing statistically significant differences (all at P<0.05). There were significant differences in the coma and trefoil of the anterior corneal surface between before and after the operation (coma: Ftime=47.848, P<0.01; trefoil: Ftime=2.497, P=0.046). Compared with before surgery, the postoperative coma was significantly increased in the two groups (all at P<0.05). There were significant differences in total corneal HOA and spherical aberration at different postoperative time points between the two groups (total HOA: Fgroup=8.093, P=0.008; Ftime=125.019, P<0.01.spherical aberration: Fgroup=4.771, P=0.037; Ftime=34.033, P<0.01). Compared with SMILE group, the total corneal HOA and spherical aberration were significantly increased in FS-LASIK group at different postoperative time points (all at P<0.05). Compared with before surgery, postoperative total HOA of the anterior corneal surface and spherical aberration at different postoperative time points were significantly increased in both groups (all at P<0.05). In both groups, the 12-month postoperative corneal spherical aberration was significantly reduced in comparison with the 1- and 3-month postoperative ones (all at P<0.05). There was a significant difference in coma between before and after surgery ( Ftime=30.829, P<0.01). Compared with before surgery, the postoperative coma was significantly increased at different time points in both groups (all at P<0.05). Conclusions:Both FS-LASIK and SMILE increase the HOA of the anterior corneal surface and the whole cornea.Compared with FS-LASIK, SMILE introduces less HOA of the anterior corneal surface and the whole cornea as well as spherical aberrations.
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Objective:To observe the clinical effect of modified Shishi Niubangzi Decoction combined with strengthening muscle-waist exercise on lumbar disc herniation (LDH).Methods:Randomized controlled trial. A total of 60 patients with LDH admitted to the Pinggu Hospital, Beijing Traditional Chinese Medicine Hospital, were enrolled as the research objects between September 2020 and September 2021. According to the random number table, they were randomly divided into the treatment group and control group, 30 in each group. Both groups were given routine basic treatments (strengthening tendons-waist exercise and three-position six-step manipulation). On this basis, the treatment group was treated with modified Shishi Niubangzi Decoction, while the control group was treated with non-steroidal anti-inflammatory drugs (ibuprofen codeine sustained-release tablets). Both groups were treated for 4 weeks. The responsive rates, back pain intensity, leg pain and numbness by Visual Analogue Scale (VAS) and lumbar function by Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) were compared between the two groups.Results:The response rate of treatment group was significantly higher than that of control group (93.3% vs. 73.3%; χ2=4.32, P=0.038). After treatment, scores of JOA (subjective symptoms, signs, activities of daily living) in the treatment group were significantly higher than those in the control group ( t=3.86, 2.71, 2.21, P<0.05). After treatment, scores of back pain (2.12±0.21 vs. 3.02±0.32, t=12.88), leg pain (2.04±0.64 vs. 2.64±0.66, t=3.58), lower limb numbness (1.75±0.24 vs. 2.41±0.70, t=4.89) in the treatment group were significantly lower than those in the control group ( P<0.01). At 1 week and 1 month after treatment, ODI scores in treatment group were significantly lower than those in control group ( t=10.22, 5.59; P<0.05). Conclusion:The modified Shishi Niubangzi Decoction combined with strengthening tendons-waist exercise can improve responsive rates, improve lumbar pain and function in LDH patients.
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Objective To investigated the effect of stenosis characteristics (vascular elasticity and plaque properties) on myocardial ischemia. Methods An ideal geometric multi-scale coronary stenosis model based on fluid-structure interaction was established, and the fractional flow reserve (FFR) was simulated to evaluate myocardial ischemia. The effects of vascular elastic wall (elastic modulus of 1 MPa) and rigid wall, plaque types (lipid-rich plaque and calcified plaque) and plaque volume on myocardial ischemia were considered separately. Results The FFRCT simulation result of vessels with elastic wall was larger than that with rigid wall under all stenosis situations. The FFRCT of vessels in lipid-rich lesions was higher than that of calcified plaque (P=0.001). The trapezoidal plaque volume was larger than the cosine plaque volume, and the FFRCT of vessels in trapezoidal plaque was smaller than that of cosine plaque (P=0.001). Conclusions Vascular elasticity is a critical factor to simulate vascular hemodynamics. In moderate stenosis, calcified plaques are more likely to induce myocardial ischemia due to the larger luminal deformation and dilation of rich lipid plaque. When the stenosis is constant, the smaller the plaque volume, the higher the FFRCT and the smaller the possibility of myocardial ischemia.
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Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.
Subject(s)
Male , Female , Humans , Laryngopharyngeal Reflux/diagnosis , Case-Control Studies , Microbiota , Outpatients , Saliva/microbiologyABSTRACT
Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.
Subject(s)
Mice , Animals , Interferon-gamma/metabolism , Interleukin-17/metabolism , Interleukin-33/metabolism , Cytokines/metabolism , Carbon Tetrachloride , Th2 Cells , Interleukin-4/metabolism , Liver Cirrhosis/pathology , Th1 Cells , Th17 Cells/pathology , ImmunityABSTRACT
Objective: To investigate the association between screen exposure and language skills in children aged 2-5 years. Methods: There were 299 children aged 2-5 years, recruited by convenience sampling from those who visited the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics for routine physical examination from November 2020 to November 2021. Their development status were evaluated by the children neuropsychological and behavioral scale (revision 2016). A self-designed questionnaire for parents was conducted to collect demographic and socioeconomic information and screen exposure characteristics (time and quality). One-way ANOVA and independent sample t test were applied to compare the differences in language development quotient of children with different screen exposure time and quality. Multiple linear regression was used to analyze the correlation between screen exposure time and quality with language developmental quotient. Multivariate Logistic regression was used to analyze the risk of language underdevelopment in children with different screen exposure time and quality. Results: Among 299 children, 184 (61.5%) were boys and 115 (38.5%) were girls, with the age of (3.9±1.1) years. The number of children with daily screen time <60, 60-120 and>120 min was 163 children (54.5%), 86 children (28.8%) and 50 children (16.7%), respectively, with the language development quotients of 94±13, 90±13, 84±14, respectively, demonstrating a statistically significant difference (F=8.92, P<0.001). Logistic regression analysis revealed that screen exposure time of 60-120 and >120 min per day were both risk factors for children's language developmental quotients (OR=2.28, 95%CI 1.00-5.17, P=0.043; OR=3.96, 95%CI 1.86-9.17, P<0.001), and co-viewing and exposure to educational programs were both protective factors for children's language developmental quotients (OR=0.48, 95%CI 0.25-0.91, P=0.024, OR=0.36, 95%CI 0.19-0.70, P=0.003). Conclusions: Excessive exposure screen time and inappropriate screen exposure habits are associated with children's poorer language development. Screen exposure time should be limited and screen use should be rational to promote children's language skills.
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Male , Female , Humans , Child , Surveys and Questionnaires , Parents/psychology , Cognition , Risk FactorsABSTRACT
Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.
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Humans , Adult , Male , Female , Middle Aged , Aged , Histones/genetics , Brain Neoplasms/pathology , Proto-Oncogene Proteins B-raf/metabolism , Glioma/pathology , Astrocytoma/pathology , MutationABSTRACT
Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.
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Humans , Early Detection of Cancer , Risk Factors , Colorectal Neoplasms/genetics , Asia , China/epidemiologyABSTRACT
Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.
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Objective @#To observe the clearance of smear layer on the root canal wall in different action time by scanning electron microscope (SEM), and to determine the optimal amount of time using sonically activated irrigation to wash root canal in clinic. @*Methods@# Fifty-six ex vivo human anterior teeth with single straight root canal were selected. After routine mechanical preparation, they were divided into two experimental groups according to different irrigating agents: saline group and EDTA group. Each group was assisted by VDW sonic activation EDDY. The saline group was divided into three subgroups according to the irrigating time: 5 s, 30 s and 50 s; EDTA group was divided into six subgroups according to the irrigating time: 5 s, 10 s, 20 s, 30 s, 40 s and 50 s. The control group did not undergo root canal irrigation. After irrigation, the root was cut longitudinally. The smear layer of crown, middle and apical of root canal wall was observed by SEM.@* Results@# After irrigating for 30 seconds, there was a significant difference between the normal saline group and the control group and the 5 second group (P<0.05), and there was no difference in the middle and apical part (P>0.05). After 50 seconds, there was a significant difference in the score of the smear layer between the apical area and the other groups (P<0.05). After irrigating for 5 seconds or 10 seconds in EDTA group, there was a significant difference between the scores of the crown and middle area of the root canal and the control group (P<0.05), and there was no significant difference in the apical area (P>0.05). There was a significant difference between the 20-40 second group and the first two groups (P<0.05). There was a significant difference between the 50 second group and the other groups (P<0.05). Comparing the cleaning effect on the smear layer after 50 seconds of irrigating between the two experimental groups, the whole root canal showed significant statistical difference (P<0.05). @*Conclusion @#The EDTA-assisted sonic activated device used for 50 seconds has the best cleaning effect.
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Objective@#To identify high risk behaviors and infection related factors among young adult males diagnosed with HIV/AIDS in Shandong Province, to provide evidence for targeted AIDS prevention and control strategies.@*Methods@#By using convient sampling method, an face to face in depth interview on HIV related behaviors was conducted among young adult males newly diagnosed with HIV/AIDS in Shandong Province in July 2021.@*Results@#A total of 31 young adult males diagnosed with HIV/AIDS were interviewed. All were male and infected through homosexuality behavior. Average age was (20.6±1.8) years. Totally 90.3% (28/31) were enrolled in tertiary education at the time of diagnosis. The findings revealed that 93.5% (29/31) of participants got infection due to unprotected homosexual behavior with the temporary partner whose HIV infection status was unknown, and 86.2% (25/29) got in touch with these temporary partner by social software. The awareness rate of knowledge about AIDS among all the participants was 100%, however, 83.9% (26/31) reported occasion condom usage while having homosexual behavior, and 16.1% (5/31) never did. Totally 74.2% (23/31) of the young adult males diagnosed with HIV/AIDS had a history of HIV testing before diagnosis.@*Conclusion@#The primary high risk behavior of HIV infection in young adult students are unawareness of HIV infection status for temporary sexual partner and the separation of knowing and doing. A targeted strategy should be developed to control the spread of HIV in young adult students.
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OBJECTIVE To analyze the efficacy and safety of polymyxin B in the treatment of carbapenem-resistant Klebsiella pneumoniae （CRKP）-bloodstream infection （BSI） in patients with hematologic malignancies. METHODS The medical records of patients with hematologic malignancies with CRKP-BSI who received polymyxin B for at least 3 days in our hospital from September 2019 to June 2021 were retrospectively analyzed. All patients were initially treated with a triple therapy namely polymyxin B+tigecycline+carbapenems for anti-infection therapy. RESULTS A total of 10 patients were enrolled as the study subjects. Eleven strains of CRKP were cultured in blood， including 10 strains of CRKP produced Klebsiella pneumoniae carbapenemase（KPC） and 1 strain of CRKP produced both KPC and metal-beta-lactamase； 9 strains were sensitive to colistin， 7 strains were sensitive to tigecycline， 5 strains were sensitive to amikacin and 2 strains were sensitive to compound sulfamethoxazole. All patients were accompanied by neutropenia， with an average duration of （14.1±6.4） days. They were all characterized by fever， chills and fatigue. After treatment， 6 patients were cured and discharged， 4 patients died of ineffective treatment of septic shock. No serious adverse events related to polymyxin B occurred in all patients. CONCLUSIONS Polymyxin B can be used as a therapeutic drug for CRKP-BSI in patients with hematological malignancies. No serious adverse event related to polymyxin B occurs during the treatment.
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Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.
Subject(s)
Humans , Glioblastoma/genetics , Exosomes/metabolism , MicroRNAs/metabolism , Prognosis , Cell Proliferation , Brain Neoplasms/genetics , Cell Line, TumorABSTRACT
OBJECTIVES@#To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.@*RESULTS@#Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.@*CONCLUSIONS@#MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.
Subject(s)
Humans , Child , Female , Male , Infant , Child, Preschool , Pneumonia , Respiratory Syncytial Virus, Human , Antibodies , Community-Acquired Infections , Hospitalization , Influenza B virus , Mycoplasma pneumoniaeABSTRACT
Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.
Subject(s)
Humans , Paclitaxel/pharmacology , Liposomes/chemistry , Ginsenosides/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Cardiotoxicity/drug therapy , Cell Line, TumorABSTRACT
Objective: To explore the method and effect of endoscopic assisted functional rhinoplasty for patients with deviated nose and deviated nasal septum, which achieve correction of nasal morphology and ventilation dysfunction. Methods: The clinical data of 226 patients with deviated nose and deviated nasal septum from June 2009 to February 2022 who were treated by endoscopic assisted functional rhinoplasty in the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 174 males and 52 females, with the age ranging from 7 to 67 years old. The effect was evaluated by subjective and objective evaluation methods. SPSS 27.0 software was used for statistical analysis. Results: All patients were followed up for 6 to 24 months, 174 cases were cured (174/226, 76.99%), 52 cases were effective (52/226, 23.01%), and the total effective rate was 100% (226/226). The difference between preoperative and postoperative facial appearance deviation was statistically significant ((6.84±2.25)mm vs (1.82±1.05)mm, t=38.94, P<0.001), and the nasal ventilation function of all patients was improved. Conclusions: Endoscopic assisted functional rhinoplasty for the patients with deviated nose combined with deviated nasal septum has the advantages of clear surgical field, fewer complications, and good result. It can achieve the purpose of simultaneous correction of nasal and ventilation dysfunction, which is recommended for popularizing in clinical application.
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OBJECTIVES@#To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls.@*METHODS@#The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing.@*RESULTS@#A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing.@*CONCLUSIONS@#High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.