Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Mild cognitive impairment （MCI） is a critical precursor stage of Alzheimer’s disease， and the development of MCI is closely associated with liver function. As a core metabolic organ， the liver regulates cognitive function through the liver-brain axis. Epidemiological studies have shown the association between liver function parameters and MCI. The liver affects cognitive function by clearing peripheral β-amyloid （mainly via the PPARα-LRP-1 pathway）， secreting hepatic factors such as FGF21 and sEH to modulate neuronal energy metabolism， and mediating oxidative stress and systemic inflammatory responses. Anti-inflammatory/antioxidant measures， dietary pattern adjustments， and aerobic exercise are currently effective strategies for regulating liver function and mitigating mild cognitive impairment. This article systematically reviews the role and mechanism of the liver-brain axis in MCI， in order to provide new perspectives for developing liver-targeted therapies for cognitive impairment.

The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Imidazoles/administration & dosage* ; Lung Neoplasms/pathology* ; Mutation ; Neoplasm Metastasis ; Oximes/administration & dosage* ; Proto-Oncogene Mas ; Proto-Oncogene Proteins B-raf/genetics* ; Pyridones/administration & dosage* ; Pyrimidinones/administration & dosage*

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

[Objective]To summarize Professor LIN Xianming's clinical experience in treating tic disorders(TD)based on the"promoting Yang to relieve stagnation"approach.[Methods]Through clinical observation,literature review,and analysis of Professor LIN's theoretical discussions and medical case records,this study systematically elaborates the etiology and pathogenesis of TD,and further explores the unique diagnostic and therapeutic approach of"promoting Yang to relieve stagnation"by supporting clinical case.[Results]Professor LIN believes that TD often arises from the gradual stagnation of Yang Qi,leading to internal Yang stasis,which further exacerbates the condition.Manifestations arise either from Yang Qi failing to nourish the mind and sinews,or from the offensive surge of constrained Yang.The traditional"calming the liver and extinguishing wind"method may hinder the development of Yang Qi in children.Therefore,he proposes the"promoting Yang to relieve stagnation"method,combining Cinnamomi Ramulus-based formulas with acupuncture at back-Shu points,which facilitates the dispersal of Yang Qi and restores proper function,thereby nourishing the mind and tendons and alleviating the tics.The differentiated application of various Cinnamomi Ramulus-based formulas,combined with the"quick and slow needling technique"applied to back-Shu points,can effectively treat TD.The attached TD case presents a pattern of depressed Yang Qi failing to flowing smoothly,accompanied with offensive surge of constrained Yang Qi,along with Yang Qi deficiency.The treatment employed Guizhi Gegen Decoction combined with stimulation of the back-Shu acupoints to disperse stagnation and activate Yang,elevate Yang and restore Yin balance,resulting in favorable therapeutic outcomes.[Conclusion]Professor LIN's approach of treating TD through"promoting Yang to relieve stagnation"has shown remarkable efficacy and is worth promoting in clinical practice.

Background Polycyclic aromatic hydrocarbons represented by benzo[a]pyrene are among the most significant occupational and environmental pollutants. Exposure to benzo[a]pyrene during pregnancy can cause delayed intellectual development in offspring, and the mechanism may be related to the expression of protocadherin (Pcdh), a key molecule for learning and memory. Objective To explore the possible role of Pcdh in impaired learning and memory function of pups caused by benzo[a]pyrene exposure during pregnancy by establishing an animal model of cognitive impairment in pups caused by benzo[a]pyrene exposure during pregnancy, and detecting the expression of Pcdh and its transcription-related factors in the hippocampal tissues of pups at different developmental stages. Methods Sixty female and male SPF-grade rats were caged in a 1:1 ratio overnight, and the successfully mated female mice were randomly divided into blank control, 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups, with 6 mice in each group. They were intraperitoneally injected with benzo[a]pyrene from the 17th to the 19th day of pregnancy to establish an exposure model. Learning and memory functions of the offspring were tested through Morris water maze on the 45th day after the birth (PND) of the pups. On the PND45 and PND75 of the pups, hippocampal tissues of 6 pups (per group) were collected respectively. The expression levels of PcdhαC1 and wings apart-like homolog (WAPL) genes and proteins were detected by fluorescence quantitative polymerase chain reaction (PCR) and Western blotting. Results The results of Morris water maze showed that there was no interaction between the escape latency time of the pups and the dose groups of 0 mg·kg⁻¹, 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ (F _{time × group}=0.515, P>0.05). The escape latency of pups decreased with increase of training time (F _time=24.678, P<0.001, F _group=12.803, P<0.001). The PCR results showed that at PND45, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). At PND75, compared with the blank group, the relative expression levels of PcdhαC1 mRNA in the 20 mg·kg⁻¹ and 40 mg·kg⁻¹ groups decreased (P<0.05), and the relative expression levels of WAPL mRNA increased (P<0.05). The Western blotting results showed that at PND45, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). At PND75, compared with the blank group, the expression levels of PcdhαC1 protein in the 10 mg·kg⁻¹, 20 mg·kg⁻¹, and 40 mg·kg⁻¹ groups decreased (P<0.05), and the expression levels of WAPL protein increased (P<0.05). Conclusion Exposure to benzo[a]pyrene during pregnancy can cause impairment in the learning and memory abilities of PND45 offspring and may alter the expression of PcdhαC1 and WAPL genes and proteins.

Objective To analyze the effect of Physio Space balance board motor control training on rehabilitation of ankle joint injuries in a prospective randomized controlled study.Methods A total of 96 patients with ankle joint injuries treated at Yunnan Provincial Hospital of Traditional Chinese Medicine from May 2022 to May 2023 were selected and randomly divided into the study group(n=48)and the control group(n=48).Both groups received conventional physical therapy.The control group underwent standard rehabilitation training,while the study group added Physio Space balance board exercise control training on top of the control group's regimen.The therapeutic effect,ankle stability[Cumberland Ankle Instability Tool(CAIT)score],ankle joint range of motion(dorsoextension,plantar flexion),pain levels,balance ability of the affected limb[mean displacement on the X-axis(Mcd)and mean displacement on the Y-axis(Msd)scores],and serum inflammatory pain factor levels[Substance P(SP),Tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),Neuropeptide(NPY)]were compared between the two groups.Results The rate of excellent and good treatment in the study group(93.75%vs.79.17%)was higher than that in the control group(P<0.05).After 1,2,3 and 4 weeks of treatment,the CAIT score of the study group was higher than that of the control group,and the VAS score was lower than that of the control group(P<0.05).After 2 and 4 weeks of treatment,the dorsiflexion and plantarflexion range of motion in the study group were higher than those in the control group(P<0.05).The Mcd and Msd scores in the study group were lower than those in the control group after 2 and 4 weeks of treatment(P<0.05).After 2 and 4 weeks of treatment,the serum levels of TNF-α,IL-6,SP and NPY in the study group were lower than those in the control group(P<0.05).Conclusion Physio Space balance board motion control training shows significant efficacy in the rehabilitation treatment of ankle joint injuries and is worthy of promotion and application.

Objective To analyze the difference of diseases between the coal mine workers and the general population inpatients by the disease spectrum in Datong City. Methods A total of 282 639 hospitalized patients in Datong City in 2023 were included as the study subjects. Participants were divided into a general population group and a coal mine workers group based on health insurance types, with 247 897 and 34 742 cases, respectively. The disease spectrum of participants in both groups was coded and analyzed according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The standardized constituent ratios of disease categories were calculated and compared between the two groups. Results Patients aged 60-<70 years had the largest standardized proportion in both cohorts (29.02% in the general population group and 33.08% in coal mine workers group). Circulatory system diseases had the highest standardized proportion in both groups. Within the top six disease categories ranked by standardized composition ratio in the coal mine workers, three demonstrated a higher burden, including neoplasms (C00-D48), symptoms, signs and abnormal clinical/laboratory findings not elsewhere classified (R00-R99), and factors influencing health status/contact with health services (Z00-Z99), compared with the general population (11.82% vs 10.44%, 12.99% vs 8.03%, and 6.17% vs 2.04%, respectively). In both groups, male workers had higher standardized constituent ratios of circulatory, respiratory, and digestive system diseases than females (coal mine workers group, 19.53% vs 14.31%, 13.56% vs 9.10%, 10.61% vs 8.43%; general population group, 26.15% vs 22.42%, 15.45% vs 11.87%, 11.52% vs 10.41%). Conversely, the ratios for conditions classified under symptoms, signs and abnormal clinical/laboratory findings not elsewhere classified (R00-R99). and factors influencing health status/contact with health services (Z00-Z99) were higher in females than males (coal mine workers group, 13.31% vs 12.68%, 7.26% vs 5.13%; general population group, 8.91% vs 7.18%, 2.35% vs 1.74%). Mental and behavioral disorders (F00-F99) were most prevalent in the 22-<50-year age group in the general population (9.92%) and in the 50-<60-year age group in coal mine workers (8.58%). The standardized proportion of respiratory system diseases ranked first in≥80-year age workers in general population group and coal mine workers group (29.54% and 26.46%, respectively). Regarding specific malignancies, unspecified malignant neoplasm of the bronchus or lung was the most common cancer among males in both groups (3.44% and 3.62%). Among females, the standardized proportion of unspecified malignant neoplasm of breast was higher in coal mine workers group than in the general population group (2.60% vs 2.09%). Conclusion Neoplasms, abnormal symptoms, and mental health disorders should be prioritized in disease prevention strategies for coal mine workers. Greater attention should be paid to mental health screening in younger populations, and medical resource allocation should be optimized according to sex-specific high-incidence cancers.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.