Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective:To construct a primary health care institutions performance evaluation index system from the perspective of health value orientation under the background of countywide medical alliances construction.Methods:From May 2021 to February 2022, preliminary screening was made on core performance evaluation indexes via literature review; purposive sampling was used to select the dean/vice dean, persons in charge of medical service, and those in charge of public health service responsible for performance evaluation at the community health service center. Then semi-structured interviews were made on the existing performance evaluation and assessment plans as well as existing problems of primary medical and health institutions. Based on the " input-process-output" performance evaluation model, the thematic framework analysis method was used to analyze the interview data, and combined with literature research results, a preliminary performance evaluation index system for primary medical and health institutions was built under the guidance of health value. From March to May 2022, the Delphi expert consultation method was used to evaluate the importance and operability of indexes. The threshold method was used to screen indexes, and analytic hierarchy process was used to calculate the weights of evaluation indexes.Results:The health value oriented performance evaluation index system for primary healthcare institutions included 3 first-level indexes, 9 second-level indexes, and 50 third-level indexes. The first-level indexes were output (0.377 3), input (0.336 3), and process (0.286 4) in descending order of weight. The top three weighted second-level indexes were health manpower(0.177 8), health literacy and health outcomes (0.157 6), as well as responsiveness and satisfaction (0.142 6). The third-level indexes included 17 medical indexes, 16 prevention indexes, and 17 medical prevention integration indexes. The top three weighted indexes for inpatient services were resident satisfaction with medical treatment (0.052 4), medical staff satisfaction (0.050 1), and responsiveness of residents seeking medical treatment (0.040 1); The top three weighted third-level indexes excluding inpatient services were resident satisfaction with medical treatment (0.052 4), medical staff satisfaction (0.050 1), and surplus funds used for personnel incentives (0.045 5).Conclusions:The performance evaluation index system of primary health care institutions built under the health value orientation is scientific, conducive to promoting the health-orientated transformation and improving the efficiency of primary health care services.

Objective:Hidden hunger remains a severe public health problem that affects millions of people worldwide.In China,challenges related to dietary imbalance and hidden hunger persist.Micronutrient inadequacy deserves more attention among adolescents,given its vital role in their growth and development;however,this problem appears to have been largely ignored.High school students,in particular,are often at a high risk of hidden hunger but have limited assessment tools available.Therefore,this study aims to revise the hidden hunger assessment scale for high school students(HHAS-HSS)in China and assess its reliability and validity.Methods:Based on a literature review,expert consultation,pre-experiment,and formal survey,a hidden hunger assessment scale was revised for high school students.The formal survey involved 9 336 high school students in 11 of the 16 cities in Anhui Province,China,and 9038 valid questionnaires were collected and included in the analysis.The item analysis,internal consistency reliability,test-retest reliability,content validity,exploratory factor analysis,and confirmatory factor analysis of the HHAS-HSS were examined.Results:The HHAS-HSS included a total of 4 dimensions and 12 items:"vegetables and food diversity"(three items),"fruits and dairy products"(three items),"micronutrient-dense foods"(four items),and"health condition and eating habits"(two items).The results showed a Cronbach's alpha of 0.758,a split-half reliability of 0.829,and a test-retest reliability of 0.793,indicating good internal consistency.Using the Bartlett's test and Kaiser-Meyer-Olkin test(KMO)to test the exploratory factor analysis presented a four-factor model of the HHAS-HSS,the KMO value was 0.820(P＜0.001),which indicated the possibility for factor confirmatory factor analysis.Using the maximum variance rotation method,four factors were obtained,and the cumulative variance explained rate was 57.974％.Confirmatory factor analysis also supported the division of the scale into four dimensions,and the fitting indices were x2=1417.656,x2/df=29.534,goodness-of-fit index=0.974,adjusted goodnesss-of-fit index=0.958,parsimonious goodness-of-fit index=0.600,normed fit index=0.938,incremental fit index=0.940,Tucker-Lewis index=0.917,comparative fit index=0.939,and root mean square error of approximation=0.056.Except for x2/df,all the indices reached the fitting standard,and the above results showed that the construct validity of the scale reached an acceptable level.Conclusions:The HHAS-HSS has good validity and reliability for Chinese high school students.It is a convenient self-report measure of hidden hunger risk.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Objective:To explore the relationships between serum lipids, CA153 level and breast cancer incidence and clinicopathological features of patients.Methods:A total of 198 patients with breast cancer diagnosed and treated at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were enrolled as the case group, and 198 healthy women were selected with 1∶1 age pairing as controls. Five milliliters of fasting venous blood was collected to measure serum lipids levels in all subjects and CA153 levels in breast cancer patients. The difference of serum lipids levels between the two groups was compared. Logistic regression model was used to analyze the risk factors of breast cancer. For 165 breast cancer patients who did not receive neoadjuvant chemotherapy, independent sample t-test was used to compare serum lipids and CA153 levels in breast cancer patients with different pathological features, and Pearson correlation analysis was used to calculate the correlation between variables and CA153. Results:The triglyceride (TG) levels in the case group and the control group were (1.22±0.73) mmol/L and (1.06±0.52) mmol/L respectively, and the difference was statistically significant ( t=2.559, P=0.011); the total cholesterol (TC) levels were (4.47±0.86) mmol/L and (4.99±0.80) mmol/L respectively, and the difference was statistically significant ( t=-6.228, P<0.001); the high-density lipoprotein cholesterol (HDL-C) levels were (1.32±0.34) mmol/L and (1.53±0.38) mmol/L respectively, and the difference was statistically significant ( t=-5.913, P<0.001). Higher TC and HDL-C levels were independent protective factors for breast cancer ( OR=0.350, P<0.001; OR=0.531, P=0.013). The TC levels in lymph node positive and lymph node negative patients were (4.36±0.73) mmol/L and (4.67±0.83) mmol/L respectively, and the difference was statistically significant ( t=-2.518, P=0.013); low-density lipoprotein cholesterol (LDL-C) levels were (2.53±0.58) mmol/L and (2.77±0.70) mmol/L respectively, and the difference was statistically significant ( t=-2.312, P=0.022). The TC levels in patients with stage Ⅰ and stage Ⅱ/Ⅲ were (4.90±0.89) mmol/L and (4.46±0.76) mmol/L respectively, and the difference was statistically significant ( t=2.855, P=0.005); LDL-C levels were (2.95±0.71) mmol/L and (2.60±0.63) mmol/L respectively, and the difference was statistically significant ( t=2.705, P=0.008). The level of CA153 in triple-negative breast cancer patients [(14.94±7.45) U/ml] was significantly higher than that in non-triple-negative breast cancer patients [(11.96±5.96) U/ml], and the difference was statistically significant ( t=2.359, P=0.020). The level of CA153 was positively correlated with the level of TG ( r=0.167, P=0.032). Conclusion:Dyslipidemia is associated with an increased risk of breast cancer. The levels of serum lipids vary among patients with different lymph node status and tumor stages. CA153 level is positively correlated with TG level to some extent.

Objective:To analyze the characteristics of cardio-metabolic risk factors coronary artery disease(CAD)patients with in-stent restenosis(ISR)after percutaneous coronary intervention(PCI).Methods:A total of 169 patients undergone primary(T1)PCI and followed up and rechecked by coronary angiography(T2)in our hospital from 2010 to 2017 were enrolled.According to the results of coronary angiography during follow-up, patients were divided into the ISR group(n=66)and the control group(non-ISR or NISR, n=103). Patients were sub-grouped into the elderly ISR group(the E-ISR group, n=17), the elderly non-ISR group(the E-NISR group, n=19), the young ISR group(the Y-ISR group, n=49)and the young non-ISR group(the Y-NISR group, n=84). Clinical data including medical history, laboratory results, and coronary angiography records during the two hospital stays were collected.Cardio-metabolic risk factors and clinical features of coronary artery disease were analyzed for the groups.Results:The levels of systolic blood pressure, glycated hemoglobin A1c(HbA1c), fasting blood glucose(FBG), the percentage of patients with diabetes or myocardial infarction(MI)history, the coronary Gensini score and the percentage of patients with triple vessel disease were higher in the ISR group than in the NISR group(128.6±16.4) mmHg vs.(123.4±10.7) mmHg, P=0.023; (7.0±1.6)% vs.(6.2±0.9)%, P<0.001; 6.6 mmol/L vs.5.7 mmol/L, P<0.001; 53.0% vs.31.1%, P=0.004; 36.4% vs.20.4%, P=0.022; 40 vs.29, P=0.01; 57.6% vs.40.8%, P=0.033). The E-ISR group had higher systolic blood pressure and a lower glomerular filtration rate than the E-NISR group(135.9±27.2) mmHg vs.(124.1±10.8) mmHg, P=0.013; 77.5±14.4 ml·min -1·1.73 m -2vs.(84.8±9.4) ml·min -1·1.73 m -2, P=0.033), but the Y-ISR group had longer hypertension history, higher levels of low-density lipoprotein and HbA1c, and higher Gensini scores than the Y-NISR group[129.7 months vs.83.1 months, P=0.008; (2.78±1.08) mmol/L vs.(2.31±0.65) mmol/L, P=0.002; (7.2±1.7)% vs.(6.1±0.9)%, P<0.001; 41 vs.29, P=0.009]. Conclusions:Clinical features are different between elderly CAD patients and young and middle-aged CAD patients with ISR after PCI, and metabolic risk factors such as blood pressure, blood lipid and blood glucose levels should be proactively controlled

Objective: To investigate the influence of mandibular distraction osteogenesis on masticatory function by analyzing the maximal bite force before and after surgery. Methods: From May 2014 to November 2015, 22 hemifacial microsomia cases, ageing from 6 to 10 years old, underwent mandibular distraction osteogenesis and their biting force data were collected. The maximal bite forces in incisor area, bilateral premolar area and molar area were measured before surgery and 1 year after surgery. Results: The average maximum bite forces in the molar area of the affected side, premolar area of the affected side, incisor area, premolar area of the unaffected side, molar area of the unaffected side were (170.6±42.8)N, (141.9±34.9)N, (89.7±18.8)N, (169.3±29.0)N and (230.2± 56.4)N respectively before surgery. Statistics indicated that most patients had uneven distribution of bite force between the affected side and unaffected side before surgery. And they changed to (198.8±44.0)N, (151.8±31.1)N, (88.9±18.0) N, (167.8±26.1)N and (234.3±52.5)N respectively 1 year after surgery, showing that the bite force in the molar area of the affected side was significantly improved by the surgery(P<0.05). Regression analysis showed that the postoperative bite force distribution had a tendency to become more symmetrical in hemifacial microsomia patients. Conclusions Mandibular distraction osteogenesis can improve the bite force of the affected side in hemifacial microsomia patients and enhance the balance of masticatory in the long-term postoperatively.

Objective: To present the overall therapy to correct mandible deformities and modify facial contour of patients who have been diagnosed as auriculo—condylar syndrome (ACS) in our hospital. Methods: We formulate effective therapeutic plan for every single patient based on digital surgical techniques. Three patient received individualized therapy, which include bilateral Distraction osteogenesis, orthodontic treatment, genioplasty, LeFort Ⅰ osteotomy, Chin augmentation with porous polyethylene implant, or mandibular contour correction with porous polyethylene implant. Results: All three patients gained satisfactory surgical results. Occlusal function and sleeping quality in 2 severe patients was significantly improved. Conclusions Clinical features of ACS is complex, which may range from mild to severe in different patients. Individualized therapeutic plan of comprehensive treatment should be established after facial deformity evaluation and surgical simulation based on surgical techniques.

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.
Aging ; genetics ; Animals ; Astrocytes ; cytology ; metabolism ; Brain ; cytology ; metabolism ; Cell Differentiation ; genetics ; Cell Division ; genetics ; Cell Proliferation ; genetics ; Gene Expression Regulation ; genetics ; Mice ; Neural Stem Cells ; metabolism ; Single-Cell Analysis ; Stem Cells ; cytology ; metabolism ; Transcriptome ; genetics