Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

Objective:To examine the distribution of pathogens that cause postoperative nosocomial infections in patients with rectal cancer(RC)and to construct a predictive nomogram for nosocomial infection.Methods:The clinical data of 1537 RC patients admitted to Sir Run Run Shaw Hospital between January 2021 and December 2022 were collected.Patients were assigned 1∶1 by propensity score matching(PSM)to the infection group(n=83)and control group(n=83)based on the occurrence of nosocomial infection.The dis-tribution and drug resistance of bacteria in patients with nosocomial infection were analyzed.Risk factors for postoperative nosocomial infection were identified by least absolute shrinkage and selection operator(LASSO)regression,and a predictive nomogram was con-structed using multivariate logistics regression.The predictive performance of the model was evaluated by receiver operating character-istic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results:A total of 93 strains of pathogens were isolated from the 83 infected patients,including 62 strains of Gram-negative bacteria(66.67%;predominantly Escherichia coli and Pseudomonas ae-ruginosa),25 strains of Gram-positive bacteria(26.88%;mainly Enterococcus faecalis),and 6 strains of fungi(6.45%;all Candida albicans).LASSO and multivariate logistics regression showed that smoking(odds ratio[OR]=3.97,95%CI=1.27-12.43),the dwelling time of drainage tube(OR=1.19,95%CI=1.08-1.30),difference in preoperative and postoperative neutrophil counts(OR=1.23,95%CI=1.01-1.49),and difference between preoperative and postoperative C-reactive protein levels(OR=1.05,95%CI=1.03-1.07)were inde-pendent risk factors for postoperative nosocomial infection in RC patients.The area under the ROC curve of the nomogram constructed based on the above factors was 0.933(95%CI=0.896-0.969).The calibration curve showed that the predicted risk was in good agree-ment with the actual observed risk of infection.In addition,DCA demonstrated that the nomogram has good clinical utility and high net clinical benefits in predicting nosocomial infection.Conclusion:The nomogram constructed in this study has a good predictive perfor-mance in postoperative nosocomial infection in RC patients.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objectives:To investigate the distribution and change of the burden of cardiovascular diseases attributable to tobacco consumption in China and the world from 1990 to 2021.Methods:Based on Global Burden of Disease(GBD)2021 database,age standardized mortality and age standardized disability-adjusted life year(DALY)rates and estimated annual percentage change(EAPC)from cardiovascular disease(including ischemic heart disease,stroke,atrial fibrillation and flutter,aortic aneurysm,peripheral artery disease)attributable to tobacco consumption were analyzed.The association of the human development index(HDI)and social demographic index(SDI)with age-standardized mortality was also analyzed.Results:Compared to 1990,the global burden of cardiovascular diseases attributable to smoking declined in 2021,age-standardized mortality decreased from 57.2/100 000 to 26.3/100 000(EAPC=-1.81%,95% CI:-2.00% to-1.63% ).The global burden of cardiovascular diseases attributable to second-hand smoke also decreased,age-standardized mortality decreased from 11.4/100 000 to 8.3/100 000(EAPC=-1.72%,95% CI:-1.91% to-1.53% ).In China,the burden of cardiovascular diseases attributable to smoking also decreased,age-standardized mortality decreased from 52.2/100 000 to 39.6/100 000(EAPC=-1.23%,95% CI:-1.44%-1.02% );the burden of cardiovascular diseases attributable to second-hand smoke decreased,age-standardized mortality decreased from 15.3/100 000 to 14.7/100 000(EAPC=-1.26%,95% CI:-1.63% to-0.90% ).Notably,the decrease in cardiovascular diseases burden attributable to second-hand smoke among Chinese women was more significant than the global level,the age-standardized mortality rate of Chinese women decreased from 17.9/100 000 to 14.5/100 000(EAPC=-2.24%,95% CI=-2.78%～-1.86% ).Among the five types of cardiovascular diseases attributable to tobacco consumption globally and in China,the age-standardized mortality and age-standardized DALY rates of aortic aneurysm,ischemic heart disease and peripheral artery disease were higher.Globally,ischaemic heart disease is the leading cause of death,accounting for 60.2% in 1990 and 61.7% in 2021,while stroke is the leading cause of death in China,accounting for 68.1% and 51.4% in 1990 and 2021,respectively.In addition,HDI and SDI are the two main factors affecting the disease burden.In regions and countries with SDI>7.2,age standardized mortality is below our forecast line.In the later part of the forecast,China's age standardized mortality showed a downward trend,possibly due to changes in tobacco control measures.Conclusions:Over the past 30 years,the burden of cardiovascular diseases attributed to tobacco consumption has decreased globally and in China.The decline in disease burden has been most pronounced among women.However,in countries and regions with an SDI below 7.2,the burden of disease remains significant high.Therefore,it is necessary to take tobacco control measures in key regions(China,East Asia,Central Europe,Central Asia and Southeast Asia)to actively reduce smoking rates and exposure to secondhand smoke in public places,so as to reduce the burden of cardiovascular diseases.

Follicular lymphoma(FL)is a type of non-Hodgkin's lymphoma,and its treatment options face many challenges.This paper discusses the pathogenesis and treatment of FL based on the clear-turbid theory in traditional Chinese medicine(TCM)."The clear and the turbid being related,and the rise and fall of qi being disorderly"is the basic pathogenesis of FL.As the disease progres-ses,"evil qi being blocked inside,and turbid evil harming the clear"aggravates,and finally"evil qi is strong and the disease progres-ses,and evil poison is generated inside".Based on this theory,the method of raising the clear and lowering the turbid and the method of dispersing the clear and removing the turbid are proposed to treat FL.The emphasis of raising the clear and lowering the turbid is to take raising and lowering as the key,movement and stillness as the pivot,and to treat the middle jiao;the emphasis of dispersing the clear and removing the turbid is to clear the triple jiao,warm the yang and invigorate the qi,and harmonize the spleen and kidney.Ca-ses are attached to illustrate,providing new ideas for the TCM treatment of FL.

Objective To investigate the distribution characteristics of Klebsiella pneumoniae(KP),hyperviru-lent Klebsiella pneumoniae(hvKP),carbapenem-resistant Klebsiella pneumoniae(CRKP),and hypervirulent car-bapenem-resistant Klebsiella pneumoniae(hv-CRKP/CR-hvKP)in the environment of general intensive care unit(ICU)at medical institutions,and provide reference for environment assessment as well as healthcare-associated in-fection(HAI)prevention and control in ICU.Methods A total of 3 336 environmental specimens were collected from general ICUs of medical institutions in Shanghai in 2019 and 2023.After strain isolation,antimicrobial suscep-tibility testing and whole genome sequencing were conducted.Results The detection rate of KP was 1.59％(n=53),among which hvKP,CRKP,and hv-CRKP/CR-hvKP accounted for 37.74％(20/53),52.83％(28/53),and 24.53％(13/53)of the total detected strains,respectively.The main types of hvKP were ST11-KL64 and ST11-KL25,CRKP were ST15-KL19 and ST11-KL25,hv-CRKP/CR-hvKP were ST11-KL25 and ST11-KL64.The main carried resistance genes included fosA,oqx AB,tet(A),blaTEM-1B,blaKPC-2,qnrS11,etc.All strains carried viru-lence genes fimH,iutA,ent A,entB,entC,entD,entE,and entF,with only one strain carrying rmp A gene.Conclusion KP contamination is widespread in general ICU environment of medical institutions,predominantly ST11 and ST15,presenting a polymorphic distribution.CRKP and hvKP account for a relatively high proportion,and multidrug resistance is serious.Co-evolution of drug resistance and virulence presents in KP,and poses signifi-cant infection and pathogenic risks to patients,necessitating enhanced clinical vigilance and preparedness for poten-tial outbreaks.

Objectives:To investigate the distribution and change of the burden of cardiovascular diseases attributable to tobacco consumption in China and the world from 1990 to 2021.Methods:Based on Global Burden of Disease(GBD)2021 database,age standardized mortality and age standardized disability-adjusted life year(DALY)rates and estimated annual percentage change(EAPC)from cardiovascular disease(including ischemic heart disease,stroke,atrial fibrillation and flutter,aortic aneurysm,peripheral artery disease)attributable to tobacco consumption were analyzed.The association of the human development index(HDI)and social demographic index(SDI)with age-standardized mortality was also analyzed.Results:Compared to 1990,the global burden of cardiovascular diseases attributable to smoking declined in 2021,age-standardized mortality decreased from 57.2/100 000 to 26.3/100 000(EAPC=-1.81%,95% CI:-2.00% to-1.63% ).The global burden of cardiovascular diseases attributable to second-hand smoke also decreased,age-standardized mortality decreased from 11.4/100 000 to 8.3/100 000(EAPC=-1.72%,95% CI:-1.91% to-1.53% ).In China,the burden of cardiovascular diseases attributable to smoking also decreased,age-standardized mortality decreased from 52.2/100 000 to 39.6/100 000(EAPC=-1.23%,95% CI:-1.44%-1.02% );the burden of cardiovascular diseases attributable to second-hand smoke decreased,age-standardized mortality decreased from 15.3/100 000 to 14.7/100 000(EAPC=-1.26%,95% CI:-1.63% to-0.90% ).Notably,the decrease in cardiovascular diseases burden attributable to second-hand smoke among Chinese women was more significant than the global level,the age-standardized mortality rate of Chinese women decreased from 17.9/100 000 to 14.5/100 000(EAPC=-2.24%,95% CI=-2.78%～-1.86% ).Among the five types of cardiovascular diseases attributable to tobacco consumption globally and in China,the age-standardized mortality and age-standardized DALY rates of aortic aneurysm,ischemic heart disease and peripheral artery disease were higher.Globally,ischaemic heart disease is the leading cause of death,accounting for 60.2% in 1990 and 61.7% in 2021,while stroke is the leading cause of death in China,accounting for 68.1% and 51.4% in 1990 and 2021,respectively.In addition,HDI and SDI are the two main factors affecting the disease burden.In regions and countries with SDI>7.2,age standardized mortality is below our forecast line.In the later part of the forecast,China's age standardized mortality showed a downward trend,possibly due to changes in tobacco control measures.Conclusions:Over the past 30 years,the burden of cardiovascular diseases attributed to tobacco consumption has decreased globally and in China.The decline in disease burden has been most pronounced among women.However,in countries and regions with an SDI below 7.2,the burden of disease remains significant high.Therefore,it is necessary to take tobacco control measures in key regions(China,East Asia,Central Europe,Central Asia and Southeast Asia)to actively reduce smoking rates and exposure to secondhand smoke in public places,so as to reduce the burden of cardiovascular diseases.

Objective To investigate the distribution characteristics of Klebsiella pneumoniae(KP),hyperviru-lent Klebsiella pneumoniae(hvKP),carbapenem-resistant Klebsiella pneumoniae(CRKP),and hypervirulent car-bapenem-resistant Klebsiella pneumoniae(hv-CRKP/CR-hvKP)in the environment of general intensive care unit(ICU)at medical institutions,and provide reference for environment assessment as well as healthcare-associated in-fection(HAI)prevention and control in ICU.Methods A total of 3 336 environmental specimens were collected from general ICUs of medical institutions in Shanghai in 2019 and 2023.After strain isolation,antimicrobial suscep-tibility testing and whole genome sequencing were conducted.Results The detection rate of KP was 1.59％(n=53),among which hvKP,CRKP,and hv-CRKP/CR-hvKP accounted for 37.74％(20/53),52.83％(28/53),and 24.53％(13/53)of the total detected strains,respectively.The main types of hvKP were ST11-KL64 and ST11-KL25,CRKP were ST15-KL19 and ST11-KL25,hv-CRKP/CR-hvKP were ST11-KL25 and ST11-KL64.The main carried resistance genes included fosA,oqx AB,tet(A),blaTEM-1B,blaKPC-2,qnrS11,etc.All strains carried viru-lence genes fimH,iutA,ent A,entB,entC,entD,entE,and entF,with only one strain carrying rmp A gene.Conclusion KP contamination is widespread in general ICU environment of medical institutions,predominantly ST11 and ST15,presenting a polymorphic distribution.CRKP and hvKP account for a relatively high proportion,and multidrug resistance is serious.Co-evolution of drug resistance and virulence presents in KP,and poses signifi-cant infection and pathogenic risks to patients,necessitating enhanced clinical vigilance and preparedness for poten-tial outbreaks.

Follicular lymphoma(FL)is a type of non-Hodgkin's lymphoma,and its treatment options face many challenges.This paper discusses the pathogenesis and treatment of FL based on the clear-turbid theory in traditional Chinese medicine(TCM)."The clear and the turbid being related,and the rise and fall of qi being disorderly"is the basic pathogenesis of FL.As the disease progres-ses,"evil qi being blocked inside,and turbid evil harming the clear"aggravates,and finally"evil qi is strong and the disease progres-ses,and evil poison is generated inside".Based on this theory,the method of raising the clear and lowering the turbid and the method of dispersing the clear and removing the turbid are proposed to treat FL.The emphasis of raising the clear and lowering the turbid is to take raising and lowering as the key,movement and stillness as the pivot,and to treat the middle jiao;the emphasis of dispersing the clear and removing the turbid is to clear the triple jiao,warm the yang and invigorate the qi,and harmonize the spleen and kidney.Ca-ses are attached to illustrate,providing new ideas for the TCM treatment of FL.