Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.

Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.

[Research progress in clinical diagnosis and treatment of osteosarcoma of the jaw].

Osteosarcoma of the jaw (JOS), is a relatively rare type of osteosarcoma, with a unique pathogenesis and pathological manifestations. The clinical manifestation of JOS is not characteristic, and it often needs to be diagnosed by combining radiological and pathological examination. At present, the conventional treatment of JOS is a comprehensive treatment based on surgery and supplemented by radiotherapy and chemotherapy. Recently, the emergence of new therapies such as immunotherapy, gene therapy, phototherapy and traditional Chinese medicine has provided more choices for treatment and brought new hope to patients with JOS. Therefore, this article summarized the current understanding of diagnosis and the latest treatment development of JOS.

[Clinical analysis of adult oculomoclonus-myoclonus syndrome with vertigo].

The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.

Effect of mechanical ventilation guided by transpulmonary pressure in acute respiratory distress syndrome patients: a systematic review and meta-analysis of randomized control trials.

OBJECTIVE: This study aimed to investigate the effect of mechanical ventilation guided by transpulmonary pressure in patients diagnosed with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Randomized control trials of ARDS patients that received mechanical ventilation guided by transpulmonary pressure vs. mechanical ventilation guided by traditional lung protective ventilation strategies in adults were retrieved by two reviewers independently from PubMed, EMBASE, The Cochrane Library, The China National Knowledge Infrastructure, and WanFang database before October 2022. The protocol has been registered on PROSPERO (CRD42022307816). The primary outcome was mortality. The secondary outcomes included mechanical ventilation days, oxygenation function and ventilation parameters, hemodynamics, and cytokines level. RESULTS: Thirteen articles (819 patients) were finally included through our search strategy. The total mortality (RR, 0.68; 95% CI, 0.54-0.85; p = 0.0006) and mechanical ventilation days (MD, -2.77; 95% CI, -4.60 - -0.94; p = 0.003) reduced when compared with the control group. Patients in the transpulmonary pressure group had higher oxygen index (MD, 40.74; 95% CI 9.81-71.68, p = 0.010) and lung compliance (MD, 7.98; 95% CI 4.55-11.41, p < 0.00001). Positive end-expiratory pressure (PEEP) was higher in the transpulmonary pressure group (MD, 5.47; 95% CI, 3.59 - 7.35; p < 0.00001). The Interlukin-6 (IL-6) level in the control group decreased obviously compared with that in the transpulmonary pressure group (SMD, -2.03; 95% CI, -3.50 - -0.56; p = 0.007). CONCLUSIONS: Mechanical ventilation guided by transpulmonary pressure tended to have a beneficial prognosis on ARDS patients. Oxygenation and lung mechanics parameters were also improved. The clinical effect of mechanical ventilation directed by transpulmonary pressure was superior to the traditional lung protective ventilation strategies in ARDS patients.

[Analysis of the clinical characteristics of 25 cases with parenchymal neuro-Behcet's disease].

Objective: To retrospectively investigate the clinical data, radiological characteristics, treatment, and outcome of patients with parenchymal neuro-Behcet's disease (P-NBD) with particular emphasis on dizziness. Methods: This was a cross-sectional study of clinical data from 25 patients with a confirmed diagnosis of P-NBD who were admitted to the Department of Neurology of the First Medical Center of Chinese People's Liberation Army General Hospital between 2010 and 2022. The median age of the population was 37 years (range: 17-85 years). Clinical data were retrospectively analyzed, including gender, age of onset, disease duration, clinical manifestations, serum immune indicators, cerebrospinal fluid (CSF) routine biochemical and cytokine levels, cranial and spinal magnetic resonance imaging (MRI) findings, treatment, and outcome. Results: The majority of patients were male (16 cases; 64.0%), the mean age of onset was (28±14) (range: 4-58 years), and the disease course was acute or subacute. Fever was the most common clinical presentation, and the complaint of dizziness was not uncommon (8/25 patients). Analysis of serum immune indices, including complement (C3 and C4), erythrocyte sedimentation rate, interleukin-1 (IL-1), IL-6, IL-8 and tumor necrotic factor-alpha were abnormal in 80.0% of patients (20/25). Most of the 16/25 patients who underwent lumbar puncture tests had normal intracranial pressure and increased CSF white cell count and protein [median values were 44 (15-380) ×106/L and 0.73 (0.49-2.81) g/L, respectively]. Of the five patients who underwent CSF cytokine tests, four patients had abnormal results; of these, an elevated level of IL-6 was most common, followed by IL-1 and IL-8. The most common site of involvement in cranial MRI was the brainstem and basal ganglia (60.0% respectively), followed by white matter (48.0%) and the cortex (44.0%). Nine cases (36.0%) showed lesions with enhancement and six cases (24.0%) showed mass-like lesions. Three patients (12.0%) patients had lesions in the spinal cord, most frequently in the thoracic cord. All patients received immunological intervention therapy; during follow up, the majority had a favorable outcome. Conclusions: P-NBD is an autoimmune disease with multiple system involvement and diverse clinical manifestations. The symptom of dizziness is not uncommon and can be easily ignored. Early treatment with immunotherapy is important and can improve the outcome of these patients.

Application analysis of cognitive nursing in thyroid surgery patients.

OBJECTIVE: The aim of the study was to explore the effect of cognitive nursing service on stress response in patients undergoing thyroid tumor surgery. PATIENTS AND METHODS: From January 2018 to June 2019, 60 patients with thyroid tumor were selected. The patients were divided into control group and experimental group with 30 cases each. Cognitive nursing was used in the observation group and routine nursing was used in the control group. RESULTS: The scores of SDS and SAS in the observation group were significantly lower than those in the control group (p < 0.05). The nursing satisfaction of the observation group was significantly higher than that of the control group (p < 0.05). The levels of systolic blood pressure, diastolic blood pressure, angiotensin Ⅱ and cortisol in cognitive nursing group were better than those in conventional group (p < 0.05). The incidence of pain and other complications in the cognitive nursing group was lower than that in the conventional group (p < 0.05). After nursing, the anxiety and depression in the study group was (34.1 ± 4.9) and (18.1 ± 5.1) respectively; the anxiety and depression of the control group were (42.8 ± 7.3) and (25.4 ± 5.9) respectively; the anxiety and depression in the study group were significantly lower than those in the control group (p < 0.05). The improvement of diastolic pressure, systolic pressure and heart rate in the study group was better than that in the control group (p < 0.05). CONCLUSIONS: The application of cognitive nursing can effectively improve the patients' cognition of disease and treatment, reduce the patients' bad mood, improve the treatment compliance, reduce the occurrence of stress reaction, and improve the safety of anesthesia and operation. Cognitive nursing intervention provides guarantee for patients' prognosis recovery, helps patients recover and discharge as soon as possible, and also has high application value, which is worth promoting and applying in major hospitals.

[The characteristics and risk factors of cardiovascular diseases and psychological status in science and technologyists].

Objectives: To investigate the prevalence and related factors of cardiovascular diseases (CVD) and psychological problems in Chinese science and technology workers. Methods: The investigation was organized and conducted by the Innovative and Development Institute of China Association of Senior Scientists and Technologists and Capital Medical University Affiliated Beijing Anzhen Hospital, and included science and technology workers from research institutions and medical institutions in China by random sampling methods through face-to-face and online questionnaire investigation from July 1, 2019 to March 31, 2021. Information including age, sex, work stress status, CVD history, sleep, depression, and anxiety were included in the questionnaire. Results: This survey included 14 552 subjects. Among them, 25.5% were suffered from CVD, 48.6% were with insomnia, 28.8% experienced depression/anxiety (including only depression, only anxiety, depression combined with anxiety), and 15.6% had CVD in combined with depression/anxiety. Taking those without CVD and depression/anxiety as reference group, multiple logistic regression analyses showed that work stress increased the risk of depression/anxiety in subjects without CVD (manageable work stress, OR=2.253, 95%CI 1.583-3.206, overwhelming work stress OR=7.899, 95%CI 5.094-12.250), and drinking increased the risk of CVD (OR=1.978, 95%CI 1.382-2.833). Moreover, overwhelming work stress (OR=4.012, 95%CI 2.515-6.399) and smoking (OR=2.342, 95%CI 1.603-3.421) increased the risk of depression/anxiety in subjects with CVD (all P<0.001). Conclusion: The high morbidities of depression/anxiety, CVD, and CVD in combination with depression/anxiety urge us to take actions to protect the heart and mental health of scientific and technological workers.

[Effects of reduced portosystemic flow on hepatic myelopathy in patients with cirrhosis after TIPS].

Objective: To investigate the impact of a reduced portacaval shunt on hepatic myelopathy (HM) in patients with cirrhosis after a transjugular intrahepatic portosystemic shunt (TIPS). Methods: Patients who developed HM after receiving TIPS at the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to June 2018 were retrospectively analyzed. HM severity was quantified by clinical spasticity index (CSI) and Fugl-Meyer Assessment (FMA) of the lower extremity. Clinical manifestations were combined with grades Ⅰ-Ⅳ. HM patients were divided into drug treatment (group A) and flow restriction group (group B) according to different treatment methods. The changes in CSI and FMA of the lower extremity after treatment were statistically analyzed in the two groups. P<0.05 was considered a statistically significant difference. Results: A total of 421 cases of cirrhosis who underwent TIPS were enrolled. Among them, 30 developed HM, with 22 in group A and 8 in group B. The incidence of HM after TIPS surgery was about 7.13%. After treatment, CSI was gradually increased and FMA of lower extremity was gradually decreased in group A, while vice-versa in group B. CSI in the two groups were differed significantly at 6, 12, 18, and 24 months after treatment (P<0.05), while the difference in FMA of the lower extremity was statistically significant at 12, 18, and 24 months after treatment (P<0.05). CSI was decreased and FMA of lower extremity was increased after treatment in patients with group A HM grade I. CSI, and FMA of lower extremity changes were statistically significant (P<0.05) when compared with patients with HM grades Ⅱ-Ⅳ. The incidence of hepatic encephalopathy was significantly lower in group B than that in group A (P=0.034), but there was no statistically significant difference between the two groups in the incidence of gastrointestinal bleeding, ascites, infection, MELD score and mortality. Conclusion: A reduced portacaval shunt can improve HM in patients with liver cirrhosis after TIPS, and drug therapy alone is effective for patients with early HM grade I.

[Epidemiological characteristics of novel coronavirus pneumonia in Shijiazhuang, China].

Objective: To analyze the epidemiological characteristics of an outbreak of novel coronavirus pneumonia (COVID-19) in Shijiazhuang, Hebei Province in 2021 and to provide scientific basis for developing improved strategies to prevent and control the outbreak of COVID-19. Methods: Descriptive analysis of the outbreak of COVID-19 in Shijiazhuang, Hebei Province was performed with SPSS 21.0 and Excel software. The statistical analysis of the incubation period was performed using the rstan package in R4.0.4. Results: As of February 14th 2021, a total of 942 local confirmed cases were reported in Hebei Province, 869 cases in Shijiazhuang, of which 847 cases were available for case information. This outbreak was mainly in rural areas, with the largest number of confirmed cases in Xiaoguozhuang village, 249 (29.4%); followed by Nanqiaozhai village, 128 (15.1%); and Liujiazuo village, 85 (10.0%). The outbreak lasted from January 2nd, 2021 to February 14th, 2021, and was mainly transmitted among the farmers as well as the students through dining parties, public gatherings and family contacts, showing an obvious time and occupation concentration trend. An analysis of 116 local confirmed cases in this outbreak with specific exposure time and onset time indicated that the median incubation period was 6 [interquartile range(IQR): 3.3, 10.0] days; whereas another report including 264 local confirmed cases with specific exposure time window showed that a median incubation period was 8.5 [95% confidence interval (CI): 1.8-18.8] days. Conclusions: This outbreak was mainly related to rural areas, and was associated with parties, public gatherings and family gatherings. Self-protection and isolation of key areas and populations at risk should be effectively implemented to avoid close contact and other measures to reduce the occurrence of COVID-19 aggregation. Based on the results of the incubation period of this outbreak, the isolation period could be recommended to be extended to three weeks.

[Prognostic analysis of patients with T1 stage high grade of bladder urothelial carcinoma and glandular differentiation].

Objective: To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation. Methods: We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes. Results: The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group (P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size (P=0.030), UCGD (P=0.003) and lymphovascular invasion (LVI) (P=0.032) were associated with disease recurrence. UCGD (P=0.036) and LVI (P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD (P=0.001), LVI (P=0.038) were the independent factors of disease recurrence. UCGD (P=0.007) and LVI (P=0.037) were also found to be the independent factors of disease progression. Conclusions: Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

[Three-dimensional movement of posterior teeth after losing the interproximal and occlusal contacts in adults].

OBJECTIVE: To observe the movement of posterior teeth after losing the interproximal and occlusal contacts in adults from the amount and speed of mesial-distal, buccal-lingual, occlusal-gingival and three-dimensional movements. METHODS: Twenty cases of metal post-core restoration from the Department of Prosthodontics, Peking University School and Hospital of Stomatology were recruited into this study, which was an observational study. The restored teeth had complete mesial, distal, and occlusal contacts before treatment. All the interproximal and occlusal contacts were removed during the preparation for the post-core. The three-dimensional positions of the post-core preparation were obtained by the intraoral scanner at the day of tooth preparation and that of post-core placement. The amounts of mesial-distal, buccal-lingual and occlusal-gingival tooth movement were measured in the software. On this basis, the amount of three-dimensional tooth movement was calculated. The speed of tooth movement was calculated based on the elapsed time between the two scans. RESULTS: Ten females and ten males with an average age of (29.5±4.9) years were recruited. The average elapsed time was (10.9±2.7) days. The amount of the mesial-distal tooth movement was (134.8±61.2) µm, of the buccal-lingual tooth movement was (110.3±39.5) µm, of the occlusal-gingival tooth movement was (104.8±57.5) µm, and of the three-dimensional tooth movement was (211.4±71.0) µm, respectively. The amounts of mesial-distal, buccal-lingual and three-dimensional tooth movements were larger in female than in male (P < 0.05). The speed of the mesial-distal tooth movement was (13.1±7.8) µm/d, of the buccal-lingual tooth movement was (10.6±4.5) µm/d, of the occlusal-gingival tooth movement was (10.1±6.8) µm/d, and of the three-dimensional tooth movement was (20.5±9.7) µm/d, respectively. The speed of mesial-distal and buccal-lingual tooth movements were larger in female than in male (P < 0.05). The speed of three-dimensional tooth movement was slightly larger in female than in male, while there was no significant difference between different genders (P>0.05). CONCLUSION: The three-dimensional position of posterior teeth changed after losing the interproximal and occlusal contacts in adults. The female had more significant and faster tooth movement than the male.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

[The analysis of clinical phenotypes and autoantibodies in juvenile dermatomyositis].

Objective: To elucidate the relationship between the myositis autoantibodies and clinical phenotypes of juvenile dermatomyositis (JDM). Methods: A total of 76 JDM patients admitted to the Children's Hospital of Chongqing Medical University from January 2017 to May 2020 were tested for myositis autoantibodies, including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). Kruskal-Wallis test and logistic regression were used to analyze the relationship between the antibodies and clinical characteristics. Results: In the 76 cases, 37 were females and 39 males. Forty-three cases (53%) were MSAs positive, among which the most common subtypes were autoantibodies against nuclear matrix protein 2 (NXP2) (15/76, 20%), melanoma differentiation-associated protein 5 (MDA5) (13/76, 17%) and transcription intermediary factor 1 gamma (9/76, 11%). While 20 cases (26%) were positive for MAAs, among which anti-Ro-52 antibody (17/76, 22%) was the most common subtype. Sixteen patients (21%) had both MAAs and MSAs. The incidences of arthritis (9 cases), fever (8 cases), skin ulcers (5 cases) and macrophage activation syndrome (MAS) (1 case) were significantly higher in the patients with anti-MDA5 antibody among the antibody groups. Dysphasia (6 cases) and edema (8 cases) mainly occurred in patients with anti-NXP2 antibody. Children with anti-MDA5 antibody were more likely to develop arthritis (OR=10.636, 95%CI: 2.770-40.844, P=0.001), skin ulcers (OR=12.500, 95%CI: 2.498-62.522, P=0.002), fever (OR=5.600, 95%CI: 1.580-19.849, P=0.008) and interstitial lung disease (ILD) (OR=23.333, 95%CI: 4.750-114.616, P<0.01). In the patients with different subtypes of MSAs, the creatine kinase value was significantly lower in the anti-MDA5 group than those in the anti-aminoacyl-tRNA synthetase (P=0.03), anti-NXP2 (P<0.01), and MSAs-negative group (P=0.013). Conclusions: Most children with JDM have positive myositis autoantibodies, and will present with different clinical phenotypes based on different autoantibodies. And children with anti-MDA5 antibodies are likely to develop ILD and MAS. Therefore the detection of myositis-specific autoantibodies is important.