The incidence and mortality rates of lung cancer have been continuously rising. Smoking is a crucial modifiable factor contributing to the high incidence of lung cancer, and quitting smoking is of great significance for the treatment and prognosis of lung cancer patients. This article systematically reviews the harms of smoking to lung cancer patients, such as carcinogenic substances triggering lung cancer, affecting the course of the disease, and the improvement of prognosis after quitting smoking. It also analyzes the current situation of smoking cessation among lung cancer patients, who face numerous difficulties and have a relatively small number of successful quitters. Meanwhile, this article provides a detailed introduction to the clinical diagnosis and treatment methods for smoking cessation interventions. This includes the explanation of the pathophysiology of smoking cessation, psychological supportive therapies [brief psychological intervention and 5A’s model (Ask, Advise, Assess, Assist, Arrange) psychological counseling], and pharmacotherapies (nicotine-based and non-nicotine-based smoking cessation medications). In addition, it covers the behavioral intervention therapies for smoking cessation, including the PRECEDE-PROCEED model, cognitive behavior theory model, capacity opportunity motivation-behavior (COM-B) theoretical model, information-motivation-behavioral skills (IMB) model, timing is right (TIR) theoretical model, and the economic incentive intervention model. Although some of the current intervention methods lack the support of clinical randomized controlled studies, existing research and practice have confirmed their positive effects on smoking cessation among lung cancer patients. It is hoped that relevant intervention methods can be further improved in the future to help lung cancer patients improve their quality of life.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Sepsis is a life-threatening organ dysfunction caused by the body's dysregulated response to infection. Reversible myocardial dysfunction caused by sepsis is known as septic cardiomyopathy. A thorough understanding of the pathogenesis of septic cardiomyopathy is crucial for early intervention to prevent its progression and improve the success rate of sepsis treatment. At present, the research on the pathogenesis of septic cardiomyopathy mainly focuses on two aspects: the systemic neuroimmune mechanism and the local changes of cardiomyocytes. The former mainly includes the autonomic nervous dysfunction mainly caused by sympathetic overactivation and the inflammatory storm induced by immune response disorder. The latter covers the dysregulation of calcium homeostasis, mitochondrial dysfunction and energy metabolism disorder of cardiomyocytes. Immune dysfunction is one of the key factors that cause the poor prognosis of patients with septic cardiomyopathy. Macrophages are sentinel cells of the body's innate immunity. Cardiac macrophages have been confirmed to be one of the most heterogeneous immune cells in the heart. According to their origin and differentiation, they can be divided into bone marrow-derived tissue infiltrating macrophages and cardiac resident macrophages, which have roles of polarization, phagocytosis, regulation of inflammatory response, and participate in innate and adaptive immunity. In the occurrence and development of septic cardiomyopathy, cardiac macrophages recruited from the blood participate in balancing the inflammation and repair of myocardial tissue through the conversion of pro-inflammatory phenotype and anti-inflammatory phenotype. Cardiac resident macrophages mediate immune phagocytosis to maintain the local homeostasis of cardiomyocytes, and the glycometabolic reprogramming of macrophages regulates the release of inflammatory factors, while macrophage metabolic reprogramming regulates the release of inflammatory factors. A deeper understanding of the biological behavior of macrophages, and regulating the polarization, metabolism and phagocytosis of cardiac macrophages, could serve as new target for the prevention and treatment of septic cardiomyopathy. Therefore, this article reviews the key pathogenesis of septic cardiomyopathy and the role of macrophages of different origins and differentiation, revealing the possibility of developing new strategies for the prevention and treatment of septic cardiomyopathy.
Humans ; Cardiomyopathies/pathology* ; Macrophages/immunology* ; Sepsis/complications* ; Myocytes, Cardiac

BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

Objective:To summarize the progress in research of economic evaluation of HIV vaccination strategies in the world, and provide reference for future decision-making and research on HIV vaccination.Methods:The key words used for literature retrieval were "HIV/AIDS", and "vaccine/vaccination" and "economic evaluation/cost-effectiveness analysis/cost-utility analysis/cost-benefit analysis/HTA". Literatures about the economic evaluation of HIV vaccination strategies published as of July 31, 2022, were retrieved from Wanfang Data (Wanfang), China Hospital Knowledge Database (CHKD), and PubMed databases. The quality of the articles was evaluated and analyzed comprehensively.Results:A total of 17 study articles with good quality were included. Results from the comprehensive analysis showed that HIV vaccination is a cost-saving or cost-effective strategy for key populations or the whole population. HIV vaccination could effectively reduce new infections and improve the quality of life of population. Factors, such as vaccine efficiency, coverage rate, price, and risk behavior change after vaccination, would affect the vaccination effect in different targeted populations.Conclusions:There were limited high-quality research data about the economic evaluation of HIV vaccination strategies. It is necessary to conduct in-depth research based on real-world evidence.

Objective:To investigate the feasibility of conducting active surveillance (AS) for low risk papillary thyroid microcarcinoma (PTMC) in China and to examine the factors in association with disease progression during AS.Methods:This study was a prospective observational research conducted from Jun. 2018 to Aug. 2022 at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Seventy-three patients with cytologically confirmed low-risk PTMC were enrolled in this study. They were followed up by ultrasonography, and the observed nodules were re-assessed whether or not to have disease progression. Disease progression was defined as having nodule enlarged more than 3 mm in any of diameters measured on ultrasound, or/and presence of suspicious lymph node metastasis.Results:The median follow-up time was 33 months. At the time of last follow-up, 16 cases (21.9%) exhibited disease progression, including 9 cases (12.3%) with suspicious lymph nodes detected by ultrasound, and 8 cases (11.0%) with lesion enlargement; one case (1.3%) exhibited both situations. The univariate chi-square analysis revealed that young patients (≤45 years old, P=0.041), presence of microcalcifications ( P=0.032), initial larger nodule (diameter greater than 7 mm, P=0.003), and elevated thyroid autoantibody levels ( P=0.008) were associated with disease progression. Multiple regression analysis showed elevated thyroid autoantibodies ( OR=4.311, P=0.030) and initial larger nodule ( OR=6.196, P=0.034) were independent risk factors for PTMC progression,respectively. Conclusions:AS for low-risk PTMC is a feasible and effective. During the observation, ultrasound can reveal suspicious lymph nodes and nodule enlargement, which are crucial indicators for assessing disease progression. Patients with initially larger nodule size and elevated thyroid autoantibody level are more likely to exhibit disease progression and should receive closer attention.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.

Objective To investigate the overweight and obesity of primary and middle school students in Sijing area of Shanghai from 2020 to 2022,so as to provide scientific basis for the intervention of childhood obesity.Methods In October 2020 and October 2022,all primary and middle school students in Sijing area underwent physical examination by cluster sampling method.A cross-sectional study was conducted to investigate the obesity and overweight in primary and middle school students of different ages and genders in Sijing area.Results In 2020 and 2022,7 766 and 10 594 students completed physical examination,respectively,and 4 626 of them underwent two consecutive physical examinations.The incidences of overweight and obesity were 15.14%and 21.89%in 2020,respectively.The incidences of overweight and obesity were 15.41%and 21.11%in 2022,respectively.There were no significant differences in the incidences of overweight or obesity between 2020 and 2022(P>0.05).In 2020,the incidences of overweight and obesity of male students were 14.91%and 24.70%;the incidences of overweight and obesity of female students were 15.40%and 18.80%,respectively.In 2022,the incidences of overweight and obesity of male students were 15.04%and 24.14%;the incidences of overweight and obesity of female students were 15.82%and 17.82%,respectively.There was no significant difference in the overweight rate between males and females(P>0.05).The incidence of obesity of male students was significantly higher than that of female students in both 2020 and 2022(P<0.05).In the students aged 12 years old,the incidence of obesity was 27.42%in 2022,which was significantly higher than that in 2020(P<0.05).There was no significant difference in the incidence of obesity between other age groups(P>0.05).Among the 4 626 children who participated in two consecutive physical examinations,the overweight/obesity rates were 14.46%/21.25%in 2020 and 16.04%/21.78%in 2022;there was significant difference in the overweight rates(P<0.05),while no significant difference was found in obesity rates(P>0.05).Among the 4 626 children,there were 2 402 boys and 2 224 girls.In 2020,the overweight/obesity rates were 13.70%/24.48%in these boys and 15.29%/17.76%in these girls.In 2022,the overweight/obesity rates were 16.07%/25.44%in these boys and 16.01%/17.72%in these girls.There was no significant difference in the incidence of overweight between these girls and boys in 2020 and 2022(P>0.05),but the obesity rate of boys was significantly higher than that of girls(P<0.05).Conclusion There are high incidences of overweight and obesity among primary and middle school students in Sijing area of Shanghai,and dietary and exercise guidances should be strengthened.Meanwhile,the incidences of overweight and obesity are higher among boys,and obesity prevention and control measures should be strengthened for boys.

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15^CKO) or Tbc1d15 knockin (Tbc1d15^CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.

ObjectiveTo observe the recovery of proprioception of the affected ankle over time after lateral ankle sprain accepting routine rehabilitation. MethodsFrom June, 2020 to June, 2022, 18 patients with lateral ankle sprain in Kunshan Rehabilitation Hospital underwent routine rehabilitation for twelve weeks. They were measured active and passive position sense of bilateral ankles using an isokinetic dynamometer before treatment, and four, eight and twelve weeks after treatment, respectively. ResultsThe active presentation difference of affected ankle reduced after treatment (F = 22.533, P < 0.001), but it was more than that of the healthy ankle at the same time (t > 4.419, P < 0.001). No significant improvement was found in passive presentation difference of affected ankle after treatment (F = 1.175, P > 0.05), and it was not significantly different from those of the healthy ankle at the same time (|t| < 0.646, P > 0.05). ConclusionProprioception of affected ankle has been impaired after lateral ankle sprain, and it can be recovered after rehabilitation, but cannot achieve the healthy level even after three months of training. Passive position sense as an index of proprioception needs more researches.