BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

ObjectiveTo investigate the association between physical activity (PA), sedentary level and exercise self-efficacy for adolescents with visual impairment, and impacts of gender, age, body mass index (BMI), degree of visual impairment and exercise self-efficacy on PA. MethodsFrom October to December, 2022, 79 students aged 13 to 18 years with visual impairment from Nanjing School for the Blind were measured PA and sedentary level with accelerometer. The average percentage of daily sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were recorded. The students fininshed the Exercise Self-Efficacy Questionnaire with the help of teachers, and their height and body mass was measured. ResultsThe average percentage of daily LPA, MVPA and ST was (15.45±5.99)%, (4.55±2.15)% and (80.00±6.99)%, respectively. Compared with the girls, the boys spent more time in LPA (F = 5.330, P < 0.05) and less in ST (F = 5.760, P < 0.05). Compared with students aged 16 to 18 years, those aged 13 to 15 years spent more time in MVPA (F = 11.292, P < 0.001) and less in ST (F = 8.279, P < 0.01). The score of exercise self-efficacy correlated with ST, LPA, MVPA and age (|r| > 0.254, P < 0.05). The result of multiple linear regression showed that the exercise self-efficacy (β = 0.224) and age (β = -0.495) were the independently factors related with MVPA, which explained 34.7% of MVPA variation. ConclusionAdolescents with visual impairment aged 13 to 18 years spend more time in sedentary, and their PA level is very low. Improvement of exercise self-efficacy may help to improve PA level of them.

Objective:To investigate the clinical effect of free anterolateral thigh perforator flap(ALTPF) in reconstruction of temporal scalp defect after blood circulation reconstruction surgery for moyamoya disease.Methods:From May 2020 to July 2022, 7 patients with scalp defect after revascularisation of moyamoya disease were treated in Department of Hand and Foot Microsurgery, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University). The patients were 4 males and 3 females, aged 33-59 years old, at 43 years old in average. There were 5 defects in left tempus and 2 in right tempus. The sizes of scalp defect were 4.5 cm × 5.5 cm-7.5 cm × 9.5 cm. Debridement and VSD management were primarily performed. After wounds were stabilised, ultrasound location of perforator vessels of ALTPFs was performed. Having confirmed that the perforator vessels were suitable for the surgical requirements, flap transfers were then performed. The descending branch of the lateral femoral circumflex artery was end-to-side anastomosed with the superficial temporal artery, and the descending branch of the lateral femoral circumflex vein was end-to-end anastomosed with the superficial temporal vein. Postoperative follow-up was conducted through outpatient clinic visits, telephone and WeChat reviews. Appearance, texture of ALTPFs and the flap donor sites were observed in follow-ups. Comparisons of the changes of nervous system before and after surgery were made. Cognitive function of the patients was assessed with the Mini Mental State Examination (MMSE), together with the Activities of Daily Living (ADL) .Results:All 7 flaps survived. One flap had vascular compromise 6 hours after surgery, and was rectified after surgical intervention. All the patients were included in the postoperative follow-up for 7-33 (average 19) months. All flaps had good appearance with soft texture. There was no obvious difference in colour comparing with the skin around the recipient region. The donor sites healed well without hypertrophic scar. Examinations of nervous system of the patients were found the same as that before surgery. Using Manual Muscle Testing (MMT), the average limb muscle strength of the patients was 4 before surgery and 4 after surgery, without change; Using the Ashworth assessment scale, the average preoperative and postoperative limb muscle tension in this group of patients was 1, without change; The Berg balance scale was used to evaluate the patient's balance function, with an average score of 42 before surgery and 42 after surgery, without any changes; There was no change in limb sensation before and after surgery; Using the MMSE, the average preoperative score and postoperative score of this group of patients were 25 points, without any change. Using the modified Barthel index scoring standard, the average preoperative score for this group of patients was 75 points, and the average postoperative score was 79 points, and the ADL of the patient had improved to various levels.Conclusion:Reconstruction of scalp defect with free ALTPF after revascularisation of moyamoya disease has obvious advantages, such as it closes the wound quickly, prevents infection and achieves a good appearance. This surgical procedure can produce a good clinical effect.

Objective: To explore the clinical application value of mixed reality technology in locating perforator vessels and assisting perforator vessel dissection to harvest anterolateral thigh flaps. Methods: Six patients who needed anterolateral thigh flap repair after resection of oral and maxillofacial tumors were recruited from the Department of Oral and Maxillofacial Surgery of Nanchong Central Hospital from January 2020 to January 2021. Before surgery, the CT angiography data of the lower limbs of the patients carrying the calibration points were imported into the data workstation to perform 3D reconstruction of the perforator vessels and surrounding tissues of the thigh, and the reconstruction results were imported into Microsoft HoloLens 2 glasses. During the operation, calibration was performed at the calibration point of the operative area so that the preoperative reconstruction results were superimposed on the operative area through Microsoft HoloLens 2 glasses. The clinical application value of mixed reality technology assisted perforator vessel location and anatomy of anterolateral femoral perforator flap was discussed from six aspects: whether the perforator vessel was reconstructed preoperatively, intraoperative calibration time, whether the actual position of the perforating vessels passing through the fascia lata fulcrum deviated from the preoperative reconstruction result within 1 cm, time required to harvest the flap, and whether the actual route of the perforator vessel was consistent with the reconstruction result, and whether the postoperative flap survived. Results : The position and course of perforating vessels were successfully reconstructed in 6 cases before the operation. The actual course of perforating vessels during the operation was consistent with the reconstruction results. The deviation between the actual position of the perforating points and the preoperative reconstruction results was within 1 cm, which met the requirements of the actual asisting of the anterolateral thigh flap. The average time of flap harvest was (70.50 ± 7.20) min. The average calibration time was (13.33 ± 5.50) min. All flaps survived. Conclusions Mixed reality technology projects the reconstruction results of anterolateral femoral perforator vessels directly into the operative area, which provides a new method for asisting localization and anatomy of anterolateral femoral flap perforator vessels and reduces the possibility of injury to perforator vessels.

Objective:To investigate the effect of methyltransferase like 14 (METTL14) on the proliferation and invasion of breast cancer (BC) cells by regulating cyclin L2 (Cyclin L2, CCNL2) through m6A modification.Methods:Cancer tissues and paracancerous tissues of BC patients in Yantaishan hospital were collected from Aug. 2018 to Feb. 2020. The expression levels of m6A, METTL14 and CCNL2 in tissues were detected by high performance liquid chromatography/mass spectrometry (HPLC/MS) and qRT-PCR. Dual-luciferase reporter assay, qRT-PCR, and western blot were used to verify the regulatory relationship between METTL14 and CCNL2. RIP experiments verified the regulatory relationship between YTH domain-containing family protein (YTHDF2) and CCNL2. Cell viability was detected by MTT method, and cell invasion ability was detected by Transwell.Results:Compared with normal cells (0.24±0.02) and tissues (0.18±0.02) , BC cells MCF-10A (0.47±0.03, t=11.05, P<0.001) and HS-578T (0.41±0.03, t=8.17, P=0.001) and BC tissues (0.39±0.02, t=12.86, P<0.001) m6A level increased. Compared with normal tissues (1.00±0.26) (0.84±0.07) , METTL14 mRNA (1.57±0.28, t=13.50, P<0.001) and protein levels (1.66±0.11, t=10.89, P<0.001) in BC tissues were significantly increased high. Compared with the control group (100.00±10.11) (1.00±0.12) , the BC cell invasion ability (54.15±6.21, t=6.69, P=0.003) and activity (0.64±0.06, t=4.65, P=0.010) were weakened. Compared with the control group (100±11.05) (1±0.13) , the BC cell invasion ability (175.31±13.45, t=7.49, P=0.002) and activity (2.16±0.16, t=9.75, P=0.002) in the METTL14 overexpression group were enhanced, and the effects of METTL14 on cell invasion (137.41±12.64, t=3.56, P=0.024) and activity (1.64±0.15, t=5.59, P=0.005) were partially reversed after m6A inhibitor treatment change. Compared with normal tissues, CCNL2 expression was down-regulated in BC tissues, and the interaction between CCNL2 and METTL14 was confirmed. Compared with the control group (1.00±0.1) (0.64±0.05) , knockdown of METTL14 could make CCNL2 mRNA (1.67±0.05) . 0.13, t=7.08, P=0.002) and protein (1.09±0.09, t=7.57, P=0.002) were up-regulated. METTL14 knockout enhanced the stability of CCNL2 mRNA through a YTHDF2-dependent pathway, compared with sh-METTL14 group (50.47±5.16) (0.52±0.05) , BC cell invasion ability of sh-METTL14+sh-CCNL2 group (71.69±6.41, t=4.47, P=0.011) and activity (0.64±0.05, t=2.94, P=0.042) were improved. Conclusion:METTL14 inhibits the expression of CCNL2 through m6A modification to enhance the invasion and activity of BC cells.

In order to investigate the apoptosis triggered by porcine circovirus type 2 (PCV2) in lymphocytes and the underlying mechanism, the levels of apoptosis and the expression levels of miRNA were examined by flow cytometry, Western blotting and real-time PCR (qPCR). The mimics or inhibitors of miR-125a-5p, an apoptosis-related miRNA, were transfected into PK-15 cells, and the apoptosis rate was examined upon overexpression or inhibition of mir-125a-5p. The target gene of mir-125a-5p was predicted by bioinformatics method, and the regulation of mir-125a-5p on the target gene was analyzed by luciferase reporter assay. The expressions of Bcl-2, Bax, cytochrome C and caspase-3 were detected by Western blotting. The results showed that exosomes secreted by PK-15 cells infected with PCV2 significantly increased the lymphocyte apoptosis rate, which was dose-dependent in certain concentration range. The expression of miR-125a-5p was dramatically increased. The apoptosis rate was increased significantly in the cells transfected with miR-125a-5p. It was predicted that there were binding sites of miR-125a-5p at Bcl-2 3'UTR by TargetScan. The luciferase activity of wild-type pmir-Bcl-2 3'UTR was inhibited significantly by miR-125a-5p mimics, but that of mutant pmir-Bcl-2 3'UTR was not changed. By Western blotting, Bcl-2 was reduced significantly, while Bax, cytochrome C and caspase-3 increased significantly, and the ratio of Bcl-2/Bax was significantly decreased. These results showed that PCV2 up-regulated the expression of miR-125a-5p through exosomes, then inhibited the expression of Bcl-2 at both mRNA and protein level, activated mitochondrial apoptosis pathway and induced apoptosis in lymphocytes.
3' Untranslated Regions ; Animals ; Apoptosis/genetics* ; Caspase 3/genetics* ; Cell Proliferation/genetics* ; Circovirus/genetics* ; Cytochromes c/genetics* ; Luciferases/genetics* ; Lymphocytes/metabolism* ; MicroRNAs/metabolism* ; Swine ; bcl-2-Associated X Protein/genetics*

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
Acute Coronary Syndrome/etiology* ; Dyspnea/etiology* ; Humans ; Pharyngitis/diagnosis* ; Pharynx ; Retrospective Studies

Objective:To investigate the changes of sphenoid sinus and related risk factors of sphenoid sinusitis after microscopic transsphenoidal pituitary adenoma resection.Methods:The clinical and imaging data of 106 patients with large pituitary adenoma in 900 Hospital of the PLA Joint Logistics Team between August 2012 and March 2015 were continually collected. The changes of accumulated blood and fluid, inflammation, mucocele, mucosa remodeling in sphenoid sinus cavity at preoperative and postoperative different time points were observed through the analysis of magnetic resonance imaging (MRI). Binary logistic multiple factors regression model was used to analyze the independent risk factors for postoperative sphenoid sinusitis.Results:MRI results showed that the blood and fluid accumulated in sphenoid sinus cavity were absorbed and dissipated 3 months after the surgery, and the saddle bone windows were covered by new mucous membrane at this time, but they were not complete; the remaining tumors in the saddle all sank into the saddle to different degrees. The reconstruction of sphenoid sinus mucosa was basically complete 6 months after the surgery. There were 7 (6.6%) cases of mucocele in sphenoid sinus and 26 (24.5%) cases of sphenoid sinusitis 3 months after the surgery among 106 patients. The results of multivariate analysis showed that growth hormone adenoma ( OR = 2.981, 95% CI 1.480-26.207, P = 0.014), preoperative sphenoid sinusitis ( OR = 12.392, 95% CI 2.927-52.462, P = 0.001), frequency of multiple transsphenoidal surgery ( OR = 14.758, 95% CI 2.431-89.584, P = 0.003) and perioperative cerebrospinal fluid leakage ( OR = 11.644, 95% CI 2.175-62.344, P = 0.004) were independent risk factors for postoperative sphenoid sinusitis. Conclusions:The evolution of sphenoid sinus cavity contents has its own rules after microscopic transsphenoidal pituitary adenoma resection. Patients with growth-hormone pituitary adenoma, sinusitis before surgery, multiple transsphenoidal surgery and cerebrospinal fluid leakage during the surgery should receive enhanced anti-infection treatment and nasal care in perioperative period to reduce the possibility of sphenoid sinusitis after surgery. The staged time of reoperation for pituitary adenoma resection by transsphenoidal approach should be about 3 months after the previous operation.

Objective:To summarize the clinical characteristics, common images, pathogens, and gene mutation types of chronic granulomatosis disease (CGD) in 19 children.Methods:The clinical manifestations, laboratory findings, treatment, and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results:The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases), and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection (19/19 cases), Bacillus Calmette Guerin (BCG)-osis (14/19 cases), lymphadenitis (14/19 cases), perianal abscess (9/19 cases), skin abscess (5/19 cases) and ulcerative colitis (2/19 cases). There were 59 positive cultures.Pathogens included fungi (9 cases), Klebsiella pneumonia (8 cases), mycobacteria (7 cases), Streptococcus Viridans (5 cases), Escherichia coli (3 cases), gram-positive bacteria (3 cases), Staphylococcus aureus (3 cases), and Burkholderia cenocepacia (2 cases). Gene mutations were found in all 19 patients, including 17 cases of CYBB, 1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations (6 cases), deletion mutations (5 cases, including 2 large fragment deletions), splice mutations (3 cases) and missense mutations (5 cases). Five mutations were novel.Splice mutations in 3 cases often led to skin abscess, perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients. Conclusions:In China, CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD, and fungi are dominant pathogens of CGD.The most common infection is respiratory infection. Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.