Under the background of climate change, the escalating air pollution and extreme weather events have been identified as risk factors for chronic respiratory diseases (CRD), causing serious public health burden worldwide. This review aims to summarize the effects of changed atmospheric environment caused by climate change on CRD. Results indicated an increased risk of CRD (mainly COPD, asthma) associated with environmental factors, such as air pollutants, adverse meteorological conditions, extreme temperatures, sandstorms, wildfire, and atmospheric allergens. Furthermore, this association can be modified by factors such as socioeconomic status, adaptability, individual behavior, medical services. Potential pathophysiological mechanisms linking climate change and increased risk of CRD involved pulmonary inflammation, immune disorders, oxidative stress. Notably, the elderly, children, impoverished groups and people in regions with limited adaptability are more sensitive to respiratory health risks caused by climate change. This review provides a reference for understanding risk factors of CRD in the context of climate change, and calls for the necessity of adaptive strategies. Further interdisciplinary research and global collaboration are needed in the future to enhance adaptability and address climate health inequality.
Climate Change ; Humans ; Air Pollution/adverse effects* ; Risk Factors ; Respiratory Tract Diseases/etiology* ; Chronic Disease ; Air Pollutants/adverse effects* ; Environmental Exposure/adverse effects*

Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

Objective:To explore the value of high resolution computed tomography（HRCT） combined with Magnetic Resonance Imaging（MRI） in the diagnosis of inner ear malformation. Methods:HRCT and MRI data of 82 patients with inner ear malformations were analyzed retrospectively. HRCT MPR and CPR reconstruction of the inner ear structure, facial nerve canal and oblique sagittal MRI reconstruction of the internal auditory canal were performed. The inner ear malformations were classified, the conditions of facial nerve canal and cochlear nerve were evaluated. The association between inner ear malformation and cochlear nerve dysplasia were analyzed by Chi-square test with continuity correction. Results:Among the 82 patients with inner ear malformations,there were 49 cases of bilateral symmetry, 11 cases of bilateral asymmetry and 22 cases of unilateral inner ear malformations. Respectively, the most prevalent types were IP-Ⅱ（42.96%）, dilatation of atrium aqueduct（18.31%） and malformations of atrium and semicircular canal 19.72%. Out of 50 cases of cochlear malformations,only 3 were isolated cochlear malformations, and the rest were accompanied by other malformations of varying degrees. In the 67 ears examined by MRI, 26（38.81%） had cochlear nerve deficiency（CND）, and the incidence of CND varied with different types of inner ear malformations. Out of 142 ears, 28（19.72%） had abnormalities of the facial nerve canal. Conclusion:HRCT combined with MRI can accurately distinguish the types of inner ear malformation and effectively evaluate the facial nerve canal and cochlear nerve, and further provides the important finger and Guide value for the clinician to formulate the reasonable treatment and the operation plan.
Humans ; Ear, Inner/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Child ; Adolescent ; Adult ; Child, Preschool ; Cochlear Nerve/diagnostic imaging* ; Facial Nerve/abnormalities* ; Cochlea/abnormalities* ; Infant ; Young Adult

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To investigate the application effect of problem-based learning (PBL) combined with scenario simulation in nursing teaching of needlestick injuries.Methods:A total of 123 undergraduates majoring in nursing were selected as research subjects from the classes of 2020 and 2021 in a medical university. The 60 undergraduates in the class of 2020 were established as control group and were given PBL teaching, and the 63 undergraduates in the class of 2021 were established as experimental group and were given PBL combined with scenario simulation. The two groups were compared in terms of theoretical score, skill examination score, and knowledge-attitude-practice (KAP) score of needlestick injury knowledge. SPSS 25.0 was used to perform the t-test, the chi-square test, and the rank sum test. Results:Compared with the control group, the experimental group had significantly higher scores of theoretical examination [(84.43±5.03) vs. (80.30±4.81), P<0.001] and skill examination [(88.40±4.26) vs. (83.55±5.84), P<0.001], as well as significantly higher scores of knowledge [(14.46±1.03) vs. (13.18±1.23), P<0.001], attitude [(52.59±3.09) vs. (48.05±3.06), P<0.001], and practice [(67.37±4.28) vs. (62.17±3.92), P<0.001] in KAP questionnaire. Conclusions:PBL combined with scenario simulation teaching can effectively improve the knowledge of protection against needlestick injuries and related skills in nursing students, enhance their awareness of needlestick injuries, and promote the protective behavior against needlestick injuries.

Objective To explore the differences in MRI signs between traumatic and non-traumatic rotator cuff tears and their correlation with the degree of rotator cuff tears.Methods A retrospective analysis was conducted on the clinical data and MRI man-ifestations of 82 patients in the trauma group and 80 patients in the non-trauma group with rotator cuff tears confirmed by arthroscopy.MRI indicators included 10 parameters:the degree of rotator cuff tear,tendon kinking-sign,tendon retraction,muscle edema,fatty degeneration,muscle atrophy,long head of the biceps tendon injury,acromion type,acromio-humeral distance(AHD),and lateral acro-mion angle(LAA).The clinical data and MRI indicators of the two groups were compared,and the correlation between MRI indica-tors and the degree of rotator cuff tears was analyzed.Results There were no significant difference in age and gender between the trauma group and the non-trauma group(P＞0.05),but the onset time of symptoms was significantly shorter in the trauma group compared to the non-trauma group(30 d vs 135 d,P＜0.001).Muscle edema,tendon kinking-sign,and long head of the biceps tendon injury were more common in the trauma group(P＜0.05),while fatty degeneration and type Ⅲ acromion were more common in the non-trauma group.The average AHD was smaller in the non-trauma group compared to the trauma group(P＜0.001).In addition,type Ⅲ acromion was more commonly seen in full-thickness rotator cuff tears,and AHD value was negatively correlated with the degree of rotator cuff tears(P＜0.05).Conclusion Muscle edema,tendon kinking-sign,and long head of the biceps tendon injury on MRI are highly suggestive of traumatic rotator cuff tears,while fatty degeneration,type Ⅲ acromion and smaller AHD indicate non-traumatic rotator cuff tears.Type Ⅲ acromion and decreased AHD increase the risk of full-thickness rotator cuff tears.

Objective:This study is to investigate the relationship of parental anger expression and symptoms in children with oppositional defiant disorder(ODD).Methods:Forty-six children with ODD and 46 age-gender-matched normal children participated.The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),guided the diagnoses.Parental anger expression and children's anger management were assessed using the State-Trait Anger Expression Inventory-2 and Children Emotion Management Scales.Results:ODD symptoms were directly predicted by maternal anger index(AI)(β=0.13,P＜0.05)and anger expression-out(AX-O)(β=0.25,P＜0.05).Children's anger cope(AC)played a mediating function to maternal AI through ODD symptoms,occupying 13％of the total effect;their AC and anger dysregulation(AD)played a mediating function to maternal AX-Othrough ODD symptoms,accounting for 29％and 18％of the total effect,respectively.Conclusion:It sug-gests that anger cope and anger dysregulation in children with oppositional defiant disordermay may play a media-ting role between maternal anger expression and oppositional defiant disorder symptoms.

OBJECTIVE To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.

Objective:To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference.Methods:It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023.Results:The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments.Conclusion:Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.