Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

To review the clinical characteristics, short-term outcomes, and risk factors of patients with infective endocarditis(IE) who underwent surgical treatment at a single center, and to summarize treatment experience.

OBJECTIVE: To investigate the clinical characteristics and prognostic of venetoclax (VEN) combined targeted therapy in acute leukemia (AL) patients with PICALM∷MLLT10 fusion gene positivity. METHODS: A retrospective analysis was conducted on 16 PICALM∷MLLT10-positive AL patients treated at the First Affiliated Hospital of Soochow University from January 2021 to August 2024. These patients were diagnosed by targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR, including newly diagnosed and relapsed/refractory (R/R) cases. The immunophenotypes, genetic features, gene mutations, and the efficacy of VEN combination targeted therapy of patients were evaluated. RESULTS: Among the 16 cases, 3 were confirmed by reverse transcription multiplex PCR, and 13 were detected through targeted RNA-seq among 528 AL patients, with a detection rate of 2.46%. The averge age of patients was (28.0±8.58) years. Patients exhibited diverse immunophenotypes, including 7 cases of acute myeloid leukemia, 5 of acute T-lymphoblastic leukemia, 1 of acute B-lymphoblastic leukemia, 1 of acute undifferentiated leukemia, and 2 of mixed-phenotype acute leukemia. Among them, 11 had extramedullary disease (EMD), 14 expressed CD7, and 12 expressed CD33. Major co-occurring mutations included PHF6 (6 cases), NOTCH1 (5 cases), and 7 cases with complex karyotypes. Of the 12 patients who received standard induction therapy, 7 did not achieve remission (PR+NR). All 4 patients treated with VEN combination therapy achieved complete remission (CR). Among the 7 induction failure cases, 4 achieved CR upon re-induction with VEN, while the remaining 3 re-induced with standard therapy, did not achieve CR. Thirteen patients received allogeneic hematopoietic stem cell transplantation, including 6 who received maintenance therapy with hypomethylating agents (HMA) alone or in combination with VEN, and seven were followed up. Survival analysis showed that the overall survival was better in the maintenance therapy group (P =0.044). CONCLUSION PICALM∷MLLT10-positive AL involves multiple lineages and demonstrates poor response to conventional chemotherapy. VEN combination therapy shows promising efficacy in both newly diagnosed and R/R patients. Post-transplant maintenance therapy with HMA alone or combined with VEN may extend survival; however, further clinical validation is required.
Humans ; Sulfonamides/therapeutic use* ; Retrospective Studies ; Prognosis ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Adult ; Male ; Female ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis* ; Risk Assessment ; Minerals/chemistry* ; Fossils ; Humans ; Drug Contamination ; Mass Spectrometry

OBJECTIVE: To evaluate the clinical efficacy of self-made anatomical tower-shaped pads combined with splint plaster fixation in the treatment of unstable 2nd to 5th metacarpal fractures and to provide a reference for clinical practice. METHODS: A retrospective analysis was conducted on 98 patients with unstable 2nd to 5th metacarpal fractures treated with self-made anatomical tower-shaped pads combined with splint plaster fixation between January 2019 and December 2022. There were 74 males and 24 females, aged from 19 to 63 years old with an average of (41.58±7.23) years old. The total active movement (TAM) score was used to evaluate the metacarpophalangeal joint function. Complications and fracture healing time were recorded. RESULTS: All patients were followed up for a period ranging from 1 to 5 months, with an average duration of (3.45±1.03) months. Among the 98 patients, anatomical alignment was achieved in 75 patients, with 68 patients still maintaining anatomical alignment after fixation removal. Functional alignment was achieved in 23 patients, with 20 patients maintaining functional alignment even after fixation removal. There were 10 patients with displacement after reduction. The average fracture healing time was (5.78±1.14) weeks, and the fracture healed well without any angular or rotational deformities. TAM score was utilized to assess the hand function of patients 3 months post-treatment. The extension range of motion (10.72±1.35)° and flexion range of motion (83.19±4.08)° of the metacarpophalangeal joint were significantly higher than the pre-treatment values of (8.25±0.68)° and (70.35±2.36)°, respectively. These differences were statistically significant (P<0.05). TAM outcomes were excellent in 92 cases, good in 5, fair in 1, and poor in none. CONCLUSION The implementation of self-made anatomical tower-shaped pad combined with splint plaster fixation is effective for the conservative management of unstable 2nd to 5th metacarpal fractures.
Humans ; Male ; Female ; Adult ; Middle Aged ; Metacarpal Bones/surgery* ; Splints ; Retrospective Studies ; Fractures, Bone/therapy* ; Casts, Surgical ; Young Adult ; Fracture Fixation, Internal/instrumentation*

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To explore the deubiquitination modification of the deubiquitinase BRCC3 in rats with neuropathic pain (NPP) treated with meridian tuina of Zhuang medicine and its analgesic molecular mechanism.Methods:Rats were divided into normal group, sham-operation group, model group, sham-tuina group, and meridian tuina of Zhuang medicine group using a random number table method, with 9 rats in each group. Except for the normal and sham operation groups, spinal nerve ligation models were prepared in all other groups. On the first day after surgery, intervention was carried out on the meridian tuina of Zhuang medicine and sham-tuina groups for 14 days, while the other three groups were not intervened; the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) of each group of rats were measured at 0 days before operation, 1, 7, and 14 days after operation. Western blot was used to detect the expressions of BRCC3 and NLRP3 proteins in spinal cord tissue, and ELISA was used to detect the level of IL-1β in serum.Results:On postoperative 7 and 14 d, compared with the model group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLPR3 and BRCC3 expression in spinal cord tissue, and a decrease in serum IL-1β levels ( P<0.05). Compared with the sham-tuina group, the meridian tuina of Zhuang medicine group showed an increase in PWMT and PWTL, a decrease in NLRP3 protein expression in spinal cord tissue, and a decrease in IL-1β levels in serum ( P<0.05). Conclusion:Meridian tuina of Zhuang medicine can alleviate pain sensitivity in SNL model rats, and its mechanism is related to the inhibition of the expression of deubiquitinase BRCC3 by meridian massage of Zhuang medicine, which increases the ubiquitination level of NLRP3 and hinders its activation, thereby blocking the immune inflammatory response mediated by inflammatory factors.