Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

Objective:To study the clinical characteristics of congenital tuberculosis (CTB).Methods:From June 2016 to February 2021, the clinical data of infants with CTB admitted to the neonatal department of our hospital were retrospectively analyzed, including their clinical characteristics, diagnosis, treatment and prognosis.Results:A total of 7 infants with CTB were enrolled into the study. 4 mothers had in vitro fertilization embryo transfer (IVF-ET) due to tubal obstruction and 2 mothers who were diagnosed of tubal tuberculosis. The 7 infants included 1 male and 6 female, 6 preterm and 1 full-term. The median age of onset was 18 d (7~30 d).All of the 7 infants had fever, 6 had shortness of breath and poor response, 5 had apnea, 3 were coughing, 1 showed pale skin colour, 1 had bilateral rales in the lung, 6 had hepatomegaly, 3 splenomegaly and 1 lymphadenopathy. Chest X-ray showed patchy exudation in 3 infants, miliary pattern of opacification in 2 infants, patchy opacification in 1 infant, bilateral increased lung markings in 1 infant. The positive rate of acid-fast bacilli (AFB) was 50% in all sputum samples. Specimens from glottic and subglottic area showed higher positive rate than oropharyngeal specimen. PCR MTB-DNA tests of sputum samples were positive in all 7 cases. 1 infant received invasive respiratory support for 1 d and died after discharge. 2 infants improved significantly after initial treatment, received 1~2 months of anti-TB therapy outside the hospital and died of severe respiratory failure. Of the 4 infants survived, 1 was cured and 3 significantly improved.Conclusions:Mothers with tubal tuberculosis receiving IVF-ET may cause high risk of CTB. Sputum AFB test and sputum PCR MTB-DNA test are preferred diagnostic tests. Genetic test of drug-resistant TB may guide clinical drug use. Glottic or deeper throat specimens can increase the positive rate.

Objective:To study the intestinal mucosal state of ulcerative colitis (UC) through UC endoscopic scores and to investigate the correlation between the endoscopic scores and clinical activity and histological scores.Methods:A retrospective analysis was performed on data of 152 patients who underwent colonoscopy or sigmoidoscopy in Nanjing Drum Tower Hospital from January 2014 to September 2019. The results were graded with 7 endoscopic scores, namely, Mayo endoscopic score(MES), modified Baron score(MBS), endoscopic activity index(EAI) , Sutherland index(DAI or UCDAI) , Rachmilewitz endoscopic index(REI), Lemann endoscopic index (LEI), and ulcerative colitis endoscopic index of severity(UCEIS). Spearman correlation coefficients between endoscopic score and partial Mayo scores, Truelove-Witts disease severity score and Nancy index (NI), Robarts index (RHI) and Geboes score (GS) were calculated respectively. Consistency of each endoscopic score among different observers was analyzed.Results:Except for the weak correlation between DAI and Truelove - Witts classification ( r= 0.469, P < 0.001), all other endoscopic scores were moderately positively correlated with clinical activity scores with significance( all P<0.001). However, the correlation between 7 endoscopic scores and histological scores was weak ( P<0.001). Except that the consistency of MBS among observers was medium, those of MES, DAI and LEI among observers were poor, and those of UCEIS, EAI and REI among observers were worse ( P<0.001). Conclusion:Endoscopic scores were moderately correlated with clinical activity indexes and weakly correlated with histological scores. However, patients with endoscopic remission may have histologic inflammatory activity, so attention should be paid to histological mucosal healing after endoscopic remission. The consistency of all 7 endoscopic scoring stystems among observers was low, and the repeatability was poor.

Objective To investigate the prevalence of nonalcoholic fatty liver disease and the risk factors in Jingyuan county of Ningxia Autonomous Region.Methods The population proportionate sampling method was applied to enroll a representative sample of 10 639 adults in Jingyuan county and the study was conducted using questionnaires and physical examinations.A total of 10 553 people were included in the analysis after excluding those with missing data.High-resolution ultrasound was used to examine the liver and fasting blood was collected in the morning for measurement of blood glucose,blood lipid,and uric acid.The participants were divided into two groups of those with and without nonalcoholic fatty liver disease;the difference in blood biochemical indexes between fatty liver and non-fatty liver groups was compared,and the logistic regression model was used to explore the risk factors affecting the prevalence of fatty liver.Results The prevalence of nonalcoholic fatty liver disease was 7.60％.The prevalence of thyroid nodules was higher in men than in women (8.60％ vs.6.82％,x2=1 1.772,P=0.001).The prevalence rate of fatty liver increased with age (x2=57.336,P＜0.001),the prevalence rates among ≥18 years-＜29 years,≥30 years-＜39 years,≥40years-＜49 years,≥50 years-＜59 years,≥60 years-＜69 years,and above 70 years were 2.92％,6.50％,8.81％,9.59％,8.08％,and 4.77％ respectively.The detection rate of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were higher in nonalcoholic fatty liver disease group than in the normal group (P＜0.05).Logistic regression analysis showed that nonalcoholic fatty liver disease group had a higher risk for overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperurcemia,and dyslipidemia (OR=5.41,12.45,2.99,1.85,2.05,3.30,1.41,2.23,and 1.98).Conclusion The incidence of nonalcoholic fatty liver in Jingyuan county of Ningxia Autonomous Region was higher.The groups of overweight,obesity,abdominal obesity,impaired fasting glucose,impaired glucose tolerance,diabetes,hypertension,hyperuricemia,and dyslipidemia were high risk factors for nonalcoholic fatty liver disease.

Objective To investigate the prevalences of the obesity and hypertension in southern mountain regions of Ningxia. Methods A cross-sectional study was conducted among a representative sample of 10 639 adults using questionnaires, physical examinations, and blood pressure measurement in southern mountain areas with a population proportionate sampling method. Results The prevalences of overweight,obesity,central obesity,high percentage of body fat,and hypertension were 33.53%,10.71%,19.50%,27.69%,and 31.57% respectively, which were 30.31%,9.62%,16.70%,24.90%,and 27.61% after age-adjustment in rural areas of Ningxia,and increased with aging(Ptrend<0.05). The prevalences of overweight,obesity,and hypertension were higher in males than those in females(P<0.05),and that of central obesity was higher in females than in males(P=0.003).The prevalences of hypertension in subjects with overweight, obesity, central obesity, high percentage of body fat were 38. 14%, 53.75%,52.69%,and 48.90%,respectively. Body mass index,waist circumference,and percentage of body fat were positively correlated with systolic and diastolic blood pressure(P<0.05). The multivariable logistic model revealed that the risk of hypertension in different types of obesity increased about 1.5 times. Conclusion There is high prevalence of obesity and hypertension among the adults in southern mountain areas of Ningxia. The prevalence of hypertension in obesity,central obesity,and high percentage of body fat is closed to or more than half of the population investigated.

Objective To investigate the clinical effects of high-density micropulse photocoagulation (HD-SDM) combined with intravitreal injection of ranibizumab for diabetic macular edema (DME).Methods Thirty-one patients (31 eyes) with DME were randomly divided into two groups.Group A (15 eyes) received HD-SDM combined with intravitreal injection of ranibizumab.Group B (16 eyes) only received intravitreal injection of ranibizumab.The best corrected visual acuity (BCVA) and central macular thickness (CMT) of the two groups before and after treatment were analyzed,and the annual injection times of the two groups were compared.Results The average annual injection times was 3.67 ± 1.11 in group A,and 9.12 ±2.63 in group B.The difference was significant between the two groups (t =2.05,P ＜ 0.05).There were significant differences in CMT before and after treatment in both groups (all P ＜ 0.05).There was no significant difference in CMT between the two groups(t =1.19,P ＞ 0.05).There were significant differences in BCVA before and after treatment in both groups (all P ＜ 0.05),but there was no significant difference before and after treatment between the two groups(all P ＞ 0.05).Conclusion Both HD-SDM combined with intravitreal injection of ranibizumab and single intravitreal injection of ranlbizumab are effective for DME,but the combining treatment can remarkably decrease the annual injection times and had a good compliance of patients,is a good choice for DME patients.

Flashing light effect on microalgae could significantly improve the light efficiency and biomass productivity of microalgae. In this paper, the baffles were introduced into the traditional flat plate photobioreactor so as to enhance the flashing light effect of microalgae. Making Chlorella sp. as the model microalgae, the effect of light intensity and inlet velocity on the biomass concentration of Chlorella sp. and light efficiency were evaluated. The results showed that, when the inlet velocity was 0.16 m/s, with the increase of light intensity, the cell dry weight of Chlorella sp. increased and light efficiency decreased. With increasing the inlet velocity, the cell dry weight of Chlorella sp. and light efficiency both increased under the condition of 500 μmol/(m2 x s) light intensity. The cell dry weight of Chlorella sp. cultivated in the novel flat plate photobioreactor was 39.23% higher than that of the traditional one, which showed that the flashing light effect of microalgae could be improved in the flat plate photobioreactor with inclined baffles built-in.
Biomass ; Chlorella ; growth & development ; Culture Techniques ; instrumentation ; Light ; Microalgae ; growth & development ; Photobioreactors

ObjectiveContrast research the operative effect of the pulmonary artery banding (PAB) in the congenital heart disease with pulmonary artery hypertension,underwent the single ventricle repair procedure in different age.Methods 49 cases,male 31 and female 18.Age (7.8 ± 3.8 ) years old,weight ( 8.82 ± 4.24) kg,percutaneous blood oxygen saturation ( SPO2 ) 0.90 ± 0.04,preoperative mean pulmonary artery pressure (mPAP) ( 54.6 ± 16.8 ) mm Hg.single ventricle 13cases,tricuspid atresia 12 cases,double outlet of right ventricle with left ventricular dysplasia 11 cases,tricuspid stenosis 5 cases,ventricular imbalance type complete atrioventricular canal defect 5 cases and cross heart cases 3 cases.divided into three groups:≤0.5 years old of 17 cases,0.5 to 2.0 years old of 17 cases,≥2.0 years old 15 cases.All cases taken PAB under anesthesia and cpb,inhaled oxygen concentration 40％,SPO2 0.85,MPAP 20 mmHg.comparatively analysis postoperative SPO2,MPAP,Ventilator using time,ICU stay time and operation mortality of the three groups.ResultsThe postoperative PAP obviously decreased.Three groups of postoperative SPO2,mPAP,ventilator using time,ICU stay time were not significantly different.More than were followed up 6-72 months,1 cases ( 1-2 months) dead in aspiration two months postoperation.the other three cases had been completed Glenn and/or Fontan.ConclusionPAB can effectively reduce the pulmonary artery pressure in the different age children with congenital heart disease and pulmonary artery hypertension,the effect is good.more than 2 years old children still PAB feasible operation,and likely to complete the Glenn and/or Fontan procedure.

Activating transcription factor 4 ( ATF4),one of the activating transcription factors,belongs to the cyclic AMP response element binding protein family.The expression of ATF4 is up-regulated by tumor micro-environmental factors.And ATF4 regulates the processes of tumor growth,infiltration,metastasis,apoptosis and drug resistance.Therefore,ATF4 might serve as a potential therapeutic target in cancer.

Objective To construct an eukaryotic expression vector of human telomerase reverso transcriptase (hTERT) gene specific shRNA, and investigate the effect of pshRNA-hTERT combined with γ-irradiation on telomerase activity and DNA damage. Methods The recombinant expression plasmid pshRNA-hTERT was constructed and transfected into Hep-2 cells. The telomerase activity was examined by the PCR-hased telomeric repeat amplification protocol (TRAP). DNA single-stranded break (SSB) and the DNA double-stranded break (DSB) were detected by Comet assay. The xenograft model of human laryngeal carcinoma with the same genetic background and different radiosensitivity (Hep-2 and Hep-2R) was established in nude mice. The mixture of pshRNA-hTERT and liposome was injected to the transplanted tumor to observe the inhibition of the tumor growth. The cell apoptosis was detected by TUNEL. The hTERT protein expression was determined by streptavidin-peroxidase conjugated method (AP). Results Recombinant expression plasmid pshRNA-hTERT was successfully constructed and transfected into Hep-2 cells. The hTERT expression inhibition rate reached 60.78 %. pshRNA-hTERT not only inhibited telomerase activity of Hep-2 inehiding the increase of telomerase activity induced by γ-irradiation, but also inhibited the repair of the SSB and DSB induced by irradiation in the human laryngeal carcinoma xenograft in nude mice with the same genetic background and different radiosensitivity. The pshRNA-hTERT combined with γ-irradiation could inhibit the growth of transplanted tumor (Hep-2: EPO = 1.79; Hep-2R: EPO = 2.01) with reduced telomerase activity and hTERT protein expression. Conclusions The eukaryotic expression vector pshRNA-hTERT could enhance the radiosensitivity of Hep-2 cells in vitro and the human laryngeal carcinoma xenograft in nude mice which had the same genetic background with different radiosensitivity.