OBJECTIVES: This study aimed to investigate the association between temporomandibular disorder (TMD) and insomnia using a two-sample Mendelian randomization (MR) approach. METHODS: Bidirectional MR analyses of two samples, TMD (n=377 277) and insomnia (n=375 359), were performed using genome-wide association study statistics published in the FinnGen database. Instrumental variables were first screened, and then inverse variance weighting (IVW) and MR-Egger were used as the main-effect assessment methods. Weighted median, weighted mode, and simple mode served as supplementary methods. We used IVW and MR-Egger to test for heterogeneity, as well as MR-Egger intercepts to assess the single nucleotide polymorphism (SNP) potential level of multiplicity effects. Sensitivity analyses were conducted based on leave-one-out to identify potentially influential SNPs. All analyses were conducted by using the two-sample MR R package and were considered statistically significant when P<0.05. RESULTS: MR analysis showed the presence of TMD on insomnia (OR=1.089, 95%CI: 1.017-1.166, P=0.014). Meanwhile, no effect of insomnia on TMD (OR=0.996, 95%CI: 0.964-1.029, P=0.816) was found. The sensitivity-analysis showed that no heterogeneity existed (P>0.05), and the presence of horizontal pleiotropy was not detected (P>0.05). Leave-one-out sensitivity analysis showed no single SNP, which may affect the causal relation. All findings indicated that the causal relationship between TMD and insomnia was not significantly affected by any individual SNP and that IV did not bias the results. CONCLUSIONS Results of MR analyses showed that TMD is a risk factor for insomnia, whereas insomnia is not a risk factor for TMD.
Humans ; Sleep Initiation and Maintenance Disorders/genetics* ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Temporomandibular Joint Disorders/complications* ; Genome-Wide Association Study

BACKGROUND:Prevention of fractures after stroke is very important,and there are currently no models to predict the occurrence of hip fractures after stroke. OBJECTIVE:To investigate the risk factors leading to hip fracture in stroke patients and to establish a risk prediction model to visualize this risk. METHODS:A total of 439 stroke patients were selected from the Affiliated Hospital of Xuzhou Medical University from June 2014 to June 2017,including 107 males and 332 females,with a mean age of(71.38±9.74)years.They were divided into fracture group(n=35)and non-fracture group(n=404)according to the presence or absence of hip fracture.Univariate and multivariate analyses were used to determine the risk factors for hip fracture after stroke.The data were randomly divided into training set(70%)and test set(30%).Nomogram predicting the risk of hip fracture occurrence was created based on the results of the multifactor analysis,and performance was evaluated using receiver operating characteristic curve,calibration curves,and decision curve analysis.A web calculator was created to facilitate a more convenient interactive experience for clinicians. RESULTS AND CONCLUSION:(1)Univariate analysis showed significant differences between the two groups in the number of falls,smoking,hypertension,glucocorticoids,number of strokes,Mini-Mental State Examination,visual acuity level,National Institute of Health Stroke Scale,Berg Balance Scale,and Stop Walking When Talking scale scores(P<0.05).(2)Multivariate analysis showed that number of falls[OR=17.104,95%CI(3.727-78.489),P=0.000],National Institute of Health Stroke Scale[OR=1.565,95%CI(1.193-2.052),P=0.001],Stop Walking When Talking[OR=12.080,95%CI(2.398-60.851),P=0.003]were independent risk factors positively associated with new hip fractures.Bone mineral density[OR=0.155,95%CI(0.044-0.546),P=0.012]and Berg Balance Scale[OR=0.840,95%CI(0.739-0.954),P=0.007]were negatively associated with new hip fractures after stroke.(3)The AUC values of nomogram were 0.956 and 0.907 in the training and test sets,respectively,and the calibration curves showed a high agreement between predicted and actual status with an area under the decision curve of 0.038 and 0.030,respectively.(4)These findings conclude that the number of falls,low bone mineral density,low Berg Balance Scale score,high National Institute of Health Stroke Scale score,and positive Stop Walking When Talking are risk factors for hip fracture after stroke.Based on this,a nomogram with high accuracy was developed and a web calculator(https://stroke.shinyapps.io/DynNomapp/)was created.

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Background Environmental noise pollution is serious, and there are few studies on the effects of long-term noise exposure during sleep on cognitive function and possible biological clock mechanism. Objective To explore the cognitive impairment induced by noise exposure during sleep in mice and possible biological clock mechanism, and to provide a theoretical basis for the protection against noise exposure. Methods Twenty male C57BL/6J mice were randomly divided into a control group and a noise-exposed group, 10 mice in each group. The noise-exposed group was exposed to sleep-period noise using a noise generator for 12 h (08:00–20:00) per day for a total of 30 d. The calibrated noise intensity was set at 90 dB. No intervention was imposed on the control group. At the end of the noise exposure, cognitive function of mice was examined using the new object recognition experiment and the open field test, and the hippocampal tissue damage of mice were evaluated by Nissl staining, ionized calcium binding adaptor molecule 1 (Iba1) immunofluorescence staining, and real-time fluorescence quantitative PCR for inflammatory factors and biological clock genes. Oxidative stress indicators in the hippocampus of mice were also detected by assay kit. Results After noise exposure during sleep period, the results of new object recognition experiment showed that the discrimination index of mice in the noise-exposed group was 0.06±0.04, which was significantly lower than that of the control group (0.65±0.13) (P<0.05). The results of open field test showed that the central activity distance of the noise-exposed group was (242.20±176.10) mm, which was significantly lower than that of the control group, (1548.00±790.30) mm (P < 0.05), and the central activity time of the noise-exposed group was (0.87±0.64) s, which was significantly lower than that of the control group, (6.00±2.86) s (P < 0.05). The Nissl staining results showed that compared with the control group, neurons in the hippocampus of the noise-exposed mice were shrunken, deeply stained, disorganized, and loosely connected. The immunofluorescence results showed that microglia in the hippocampus of the noise-exposed mice were activated and the expression of Iba1 was significantly increased compared with those of the control group (P<0.05). The real-time PCR results of showed that the mRNA levels of the biological clock genes Clock, Per2, and Rev-erbα were significantly increased compared with those of the control group (P<0.05), and the mRNA level of Per1 was significantly decreased compared with that of the control group (P<0.05); and the mRNA levels of IL-18, IL-6, iNOS, and NLRP3 in the hippocampal tissues of mice were significantly increased compared with those of the control group (P<0.05). The results of oxidative stress evaluation showed that compared with the control group, reduced glutathione content was significantly reduced in the noise-exposed group (P<0.001). Conclusion Noise exposure during sleep period can lead to the destabilization of biological clock genes in hippocampal tissues and trigger hippocampal neuroinflammation, which can lead to the activation of microglia and cause cognitive impairment in mice.

This article summarizes and organizes relevant publications in journals, along with a review of medical history, systematically summarizing the development process of dental alveolar surgery in China. The initial establishment phase (1935—1952) marked the starting point of Chinese Alveolar Surgery. Despite the impact of wars, it laid the foundation for subsequent research and practice. During the early development phase (1953—1966), the "Chinese Journal of Stomatology" was founded, which promoted the development of Alveolar Surgery. Research focused on tooth extraction methods and complications. Tooth Transplantation and Preprosthetic Surgery gradually began to take off. The stagnant phase (1967—1977) occurred due to the interruption of international exchanges, leading to an almost complete halt in the development of Alveolar Surgery. Entering the rapid catch-up phase (1978—1985), Alveolar Surgery scholars in China began striving to overcome the stagnation of the previous decade. While some progress was made, no significant innovative achievements emerged. In the scientific development phase (1986—2010), clinical research, basic experiments, and paper writing in modern Chinese Alveolar Surgery began to adhere to scientific standards with the rise of experimental medicine. The exploration and innovation stage (2011—2023) is the current development phase, during which Chinese Aveolar Surgery has reached its peak, making substantial progress in technology, clinical practices, and basic research, gradually reaching or even surpassing international advanced levels. Looking back at the development history in China, we can find the wisdom and hard work of the older generation of Alveolar Surgery scholars. However, contemporary challenges and issues, such as standardizing technology, promoting clinical practices, and talent cultivation, need to be addressed by present-day Alveolar Surgery professionals as they forge ahead.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients. METHODS: This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group. RESULTS: We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37-2.59, P  <0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29-3.85, P  = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51-2.03, P  = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58-4.78, P  = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period. CONCLUSIONS The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.
Humans ; Prospective Studies ; East Asian People ; Disease Progression ; Severity of Illness Index ; Pulmonary Disease, Chronic Obstructive/epidemiology*

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

Objective To investigate the impact of PD1-TCF1+CD8+ stem-like memory T cells on immunotherapy prognosis and tertiary lymphoid structure in tumors. Methods Pathological tissue sections were collected from 33 patients treated with immunotherapy, 18 cases of NSCLC and 15 cases of ESCC. The expression of PD1-TCF1+CD8+T cells was detected through quantitative analysis by multiplex immunofluorescence. Survival curves were described by the Kaplan-Meier method. Pearson's correlation test was used for correlation analysis. Results The high levels of PD1-TCF1+CD8+T cells had a better PFS in NSCLC and ESCC cohorts. In the NSCLC cohort, high levels of PD1-TCF1+CD8+ T cells were significantly and positively correlated with the number (P=0.0151) and size (P=0.0007) of TLSs. Conclusion In patients with NSCLC and ESCCs, high PD1-TCF1+CD8+ stem-like memory T cell expression indicates improved prognosis and immune response and is associated with the formation of TLSs in the tumor microenvironment of NSCLC.

【Objective】 To analyze and mine the prescription rules of traditional Chinese medicine enema treatment of chronic kidney disease （CKD） in CNKI platform journals based on data mining and network pharmacology so as to find high-frequency core Chinese medicines and predict the potential targets of core Chinese medicines and explore the mechanism of action of core Chinese medicines in the treatment of CKD. 【Methods】 Taking CNKI as the data source， we retrieved the clinical literature of traditional Chinese medicine enema in the treatment of CKD. SPSS modeler 18.0 statistical software was used for statistical processing and association rule analysis. IBM SPSS statistics 21 statistical software was used for cluster analysis. BATMAN-TCM and TCMSP were used to retrieve the effective components and related targets of drugs. Genecards， OMIN， Drugbank， DisGenet， TTD， and PharmGkb databases were used to retrieve disease-related targets， and Venny platform was used to screen disease and drug intersection targets. We used STRING database to obtain relevant documents， Cytoscape 3.8.2 software for visual analysis， Metascape database for enrichment analysis， Wechat website to draw bubble diagram， and AutoDockTools-1.5.6 software for molecular docking prediction. 【Results】 We selected 276 effective prescriptions involving 120 traditional Chinese medicines. The frequency of 19 traditional Chinese medicines was more than 10. Totally 18 core drug combinations were obtained. Cluster analysis could be divided into four categories. The visual net-work analysis shows that “rhubarb， dandelion， oyster， Salvia miltiorrhiza and aconite” are highly correlated and occupy the core position. Through the prediction of the potential targets of five core drugs， 659 “drug disease” intersection targets and 173 core targets were obtained， of which “MAPK1， AKT1 and STAT3” are the key targets， “progesterone， neocryptotanshinone Ⅱ and emodin”. It is predicted that it may play a role in “PI3K Akt signal pathway， MAPK signal pathway， JAK-STAT signal pathway”. Molecular docking showed that the key components have good binding activity with key targets. 【Conclusion】 Based on data mining and network pharmacology， traditional Chinese medicine enema treatment of CKD mainly uses rhubarb as the main drug， assisting warming yang to remove blood stasis and turbidity relief drugs. The key components of its core drug can act on PI3K-Akt by regulating key targets such as PIK3R1. Signal pathways and other pathways play a role in providing new ideas for the treatment of this disease with traditional Chinese medicine enema， medication strategies for clinical prescriptions， and a basis for follow-up further research.

Objective:To analyze the characteristics of sleep disorders in patients with Parkinson disease (PD) and to explore the relationship between respiratory events and rapid eye movement sleep with hypotonia.Methods:Thirty-nine PD patients compared with 75 controls matched with gender, age and body mass index(BMI) were collected in the Dalian Municipal Central Hospital from January 1, 2019 to September 31, 2019. Both groups underwent polysomnography monitoring. The characteristics of sleep disorders were analyzed and discussed.Results:Apnea and hypopnea index (AHI) during total sleep, AHI during non-rapid eye movement(NREM) sleep, AHI during rapid eye movement (REM) sleep, obstructive apnea index, mixed apnea index, central apnea index, total apnea index, hypopnea index, the time with pulse oximetry <90% and oxygen desaturation index in the PD group were lower than those in the control group: 3.70(0.80, 20.00) /h vs. 17.30(7.30, 28.20)/h, 2.30(0.70, 13.90)/h vs. 15.20(4.90, 27.50)/h, 2.30(0.00, 29.80)/h vs. 16.90(5.70, 39.50)/h, 0.30(0.00, 5.10)/h vs. 3.10(0.50, 7.80)/h, 0.00(0.00, 0.20)/h vs. 0.20(0.00, 0.60)/h, 0.00(0.00, 0.30)/h vs. 0.30(0.00, 0.80)/h, 0.70(0.00, 6.00)/h vs. 3.90(0.80, 10.70)/h, 1.70(0.50, 8.90)/h vs. 8.70(2.70, 14.90)/h, 0.00(0.00, 0.40)min vs. 0.20(0.00, 1.70)min, 4.10(1.10, 18.40)% vs. 16.50(9.30, 30.80)%, and the differences were statistically significant ( P<0.05). The mean pulse oximetry and minimum pulse oximetry in the PD group were higher than those in the control group: 96.00(95.00, 97.00)% vs. 95.00(94.00, 96.00)%, 89.00(82.00, 91.00)% vs. 85.00(81.00, 89.00)%, and the differences were statistically significant ( P<0.05). PD group was divided into PD with RSWA group (PD + RSWA) and PD without RSWA group (PD-RSWA) according to whether there was atonia or not. AHI during REM sleep in the PD+RSWA group was lower than that in the PD-RSWA group: 0.00(0.00, 5.40)/h vs. 5.75(0.52, 34.57)/h, and the difference was statistically significant ( P<0.05). Conclusions:PD has a protective effect on nocturnal respiratory events, which may be due to the increased muscle tone of upper airway.