BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.

Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin′s team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class Ⅲ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.

Objective:To investigate clinical characteristics of cerebrovascular disease complicated with secondary epilepsy in the elderly, and to provide the targeted health care measures.Methods:The 106 elderly patients with epilepsy secondary to cerebrovascular diseases treated in Three Gorges Hospital Affiliated to Chongqing University were enrolled as the epilepsy group, and another 106 patients with single cerebrovascular disease without secondary epilepsy during same period were included as the control group.Clinical features and epileptic seizure activity were observed and analyzed, and the targeted health care measures were developed.Results:The proportions of patients with cerebral hemorrhage, cerebral lobe infarction, cortical dysfunction and abnormal brain waves were higher in the epilepsy group [ 66.99%(71 cases), 68.87%(73 cases), 83.02%(88 cases), 70.75%(75 cases), respectively]than in the control group(43.40% or 46 cases, 46.23% or 49 cases, 61.32% or 65 cases, 53.77% or 57 cases)( χ2=11.921、11.121、12.424、6.505, all P<0.05). NFD scores before treatment had no significant difference between the epilepsy group and the control group(22.7±4.8 vs.23.4±5.1, t=1.029, P=0.152). NFD score after 3 months of treatment was higher in the epilepsy group than in the control group(14.3±2.9 vs.10.1±2.5, t=11.294, P=0.000). Conclusions:Epilepsy is a common complication of various cerebrovascular diseases, among which the cerebral hemorrhage is the most common.Polyloencephalopathy and cortical involvement can increase the risk of epilepsy in patients with cerebrovascular diseases.Therefore, it is very important to provide the necessary treatment and health care, so as to reduce the impact of epileptic seizure on the disease condition and improve prognosis in patients with cerebrovascular disease.

One hundred eighty-four cases of awake craniotomy in Xijing Hospital from September 2010 to June 2019 were retrospectively included in the study.Patients were divided into Asleep-Awake-Asleep (AAA) group and monitored anesthesia care (MAC) group.In AAA group, general anesthesia was used in the early arousal period, sedatives and analgesics were stopped during the arousal period, and the bispectral index (BIS) value was maintained at 60-80 in the late arousal period.In MAC group, dexmedetomidine and remifentanil were intravenously infused in the early arousal period, and the BIS value was maintained at 60-80 in the late arousal pericd.Dexmedetomidine and remifentanil infused were reduced or stopped according to the Observer′s Assessment of Altertness/Sedation score during the arousal period, so that the patient could be awakened at any time, and the BIS value was maintained at 60-80 in the late arousal period.Compared with AAA group, the consumption of local anesthetic and remifentanil was significantly decreased, the operation and anesthesia time was shortened, the requirement for rescue analgesia was decreased, mean arterial pressure, end-tidal pressure of carbon dioxide (P ETCO 2) and partial pressure of arterial carbon dioxide (PaCO 2) were increased and partial pressure of arterial oxygen (PaO 2) was decreased after laryngeal mask insertion or sedation, and heart rate and PaO 2 were decreased, P ETCO 2 and PaCO 2 were increased after awakening in group MAC ( P<0.05). There were no significant differences in anesthesia failure rate in the awake craniotomy, incidence of adverse events during the arousal period, intraoperative incidence of tachycardia/bradycardia and hypertension/hypotension, Observer′s Assessment of Alertness/Sedation score during the arousal period, rate of postoperative visual analogue scale score>5 after surgery, postoperative requirement for rescue analgesia, neurological deficit rate and rehabilitation discharge rate between the two groups ( P>0.05). Compared with those after laryngeal mask insertion or after sedation, mean arterial pressure, heart rate, P ETCO 2 and PaCO 2 were significantly increased, and PaO 2 was decreased after awakening in AAA group ( P<0.05), and no statistically significant change was found in the parameters mentioned above after awakening in MAC group ( P>0.05). In summary, MAC shortens the operation and anesthesia time, no artificial airway is required, and it is suitable for the short time and minor operation.AAA has a better hemodynamics and oxygenation in the early arousal period, but the patient′s stress is more obvious after awakening, and effective prevention and intervention are needed.

With the continuous development of bioinformatics technology and precision medicine, genetic mechanism investigations of genetic diseases including cleft lip and palate (CLP) have been getting more and more attention. Researchers have focused on the coding sequence of the genome and successfully found many CLP causative mutations, but there still remain some unsolved questions. In recent years, researchers′ vision has gradually shifted to non-protein coding region of the genome. This article reviews several coding sequence mutations, non-protein coding variants and their genetic mechanisms discovered in CLP researches.

Objective To study the friction between brackets and archwires and the influential factors. Methods To test the friction of six combinations of canine bracket and stainless steel archwire, and to calculate the critical contact angles for each combination. Results The friction maintains stability with slight changes when the contact angle is smaller than the critical contact angle. The friction increases linearly when the contact angle is larger than the critical contact angle. The friction of different combinations of bracket-archwire are different and the critical contact angles are also different. Conclusion The critical contact angle influences the friction between bracket and archwire significantly. The critical contact angle is relevant to both the structure of the bracket and the size of the archwire.

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate (NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies (GWAS) have uncovered dozens of single nucleotide polymorphism (SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants in Han and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations. Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Genome-Wide Association Study ; Humans ; Infant ; Logistic Models ; Machine Learning ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide ; Retinol-Binding Proteins, Plasma ; genetics ; Risk Assessment

Objective:To study the frequency of electrical stimulation affect the atrophy recovery of mouse soleus muscle.Method:Sixty mice,30 of them were randomly divided into blank control group (Con) and atrophy model group (Atro) and validated this model after 1 week.The other 30 mice were randomly divided into three groups:the natural recovery group (Rec),the exercise intervention group (Exer),the electroacupuncture intervention group (Elec) after making them atrophy.Atrophy model group were plaster fixed one week.Natural recovery group was natural fed two weeks after removing the plaster.Exercise intervention group runs 1 hour at 16m/min speed two weeks.EA intervention group were stimulated 15min daily for 2 weeks on hind limb,with pulse duration 0.35ms,frequency 50Hz,for 2 weeks.Frozen sections and Immunofluorescence were used to measure the cross-sectional area of muscle fibers.ATPase staining was used to detect the muscle fiber type changing,and Western Blot to detect soleus muscle Troponin I-SS (TNNI1) and Troponin I-FS (TNNI2) protein expression.Result:The soleus muscle in Atro group showed significant change in cross-sectional area and wet weight compared with Con group(P＜0.01),The expression of TNNI1 and TNNI2 protein was also significantly different from that of Con group (P＜0.05).Compared with the Rec group,the cross-sectional area of slow muscle and fast muscle in the Exer and Elec groups significantly increased (P＜0.05),TNNI1 protein expression significant ly increased (P＜0.01),TNNI2 protein was no significant difference detected(P＞0.05).Conclusion:The middle low frequency electroacupuncture intervention can effectively increase the cross-sectional area of muscle fibers,in particular,increase the TNNI1 and TNNI2 protein expression of slow muscle fibers.It is as effective as exercise intervention to promote recovery of disuse muscular atrophy.

Inflammatory bowel disease (IBD) is an intestinal immune-dysfunctional disease worldwide whose prevalence increasing in Asia including China. It is a chronic disease of the gastrointestinal tract with unknown cause. Exosomes are small vesicles in various body fluids. They have diameters of 40-120 nm, and one of their functions is long-distance transfer of various substances. In this study, we investigated the contents of salivary exosomes in patients with IBD and in healthy controls to explore a new biomarker in patients with IBD. In this study, whole saliva was obtained from patients with IBD (ulcerative colitis (UC), n = 37; Crohn's disease (CD), n = 11) and apparently healthy individuals (HC, n = 10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The results showed that more than 2000 proteins were detected in salivary exosomes from patients with IBD. Through gene ontology analysis, we found that proteasome subunit alpha type 7 (PSMA7) showed especially marked differences between patients with IBD and the healthy controls, in that its expression level was much higher in the CD and UC groups. This exosomal protein is related to proteasome activity and inflammatory responses. So we conclude that in this research, salivary exosomal PSMA7 was present at high levels in salivary exosomes from subjects with IBD. It can be a very promising biomarker to release the patients from the pain of colonoscopy.
Animals ; Biomarkers ; metabolism ; Female ; Humans ; Inflammatory Bowel Diseases ; metabolism ; Male ; Proteasome Endopeptidase Complex ; metabolism ; Salivary Proteins and Peptides ; metabolism