Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

Objective:To evaluate the efficacy of combined cricopharyngeal myotomy (CPM) and autologous fat injection laryngoplasty (AFIL) in the management of dysphagia secondary to glossopharyngeal and vagal nerve injury.Methods:This retrospective cohort study collected the clinical data of 18 patients with persistent dysphagia due to glossopharyngeal and vagus nerve injuries, who underwent concurrent cricopharyngeal myotomy (CPM) and autologous fat injection laryngoplasty (AFIL) at the Department of Otolaryngology, Peking Union Medical College Hospital, from January 2017 to December 2024. Pre-and postoperative assessments included electronic flexible laryngoscope, the Chinese version of Swallow Quality-of-Life Questionnaire (CSWAL-QOL), videofluoroscopic swallowing study (VFSS), body weight changes, and nasogastric tube (NGT) removal status with routine follow-up. The comparison of swallowing function before and after surgery was conducted using paired samples t-test and χ2 test. Results:The study cohort comprised 10 male and 8 female patients, with ages ranging from 33 to 70 years (mean±SD: 53.8±10.5). All surgical procedures were completed successfully without complications. During the 6-to 24-month follow-up period, 10 of the 13 patients who were initially nasogastric tube-dependent achieved successful decannulation. Compared with preoperative values, postoperative measurements demonstrated statistically significant improvements across all parameters: mean body weight increased from (56.95±9.14) kg to (59.22±8.72) kg ( t=3.689 , P<0.01), CSWAL-QOL scores improved from 91.89±17.81 to 130.83±25.42 ( t=6.921 , P<0.01), while, both VFSS scales showed marked reductions (VFSS-SWAL: 6.78±1.40 to 3.39±1.61, t=-8.001, P<0.01; PAS: 6.56±1.15 to 2.94±1.26, t=-10.114, P<0.01). Conclusions:Combined CPM and AFIL represents an effective surgical approach for dysphagia following glossopharyngeal and vagal nerve injury, thereby demonstrating significant improvements in both swallowing function and quality of life.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveTo analyze the correlation between the clinical symptoms， signs， syndrome characteristics and laboratory indicators of cough variant asthma （CVA） and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM， and the nature and location of CVA were extracted. Sample cluster analysis （Q clustering） and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough， accompanied by symptoms such as itchy throat， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， chest tightness， hoarseness， bitter mouth， poor appetite， and skin itching. Factor analysis showed that the disease was located in the lung， involving the liver， spleen， and kidney. The pathological factors involved Yin deficiency， Yang deficiency， wind factor， dampness factor， Yin factor， and Qi stagnation. Cluster analysis revealed four syndrome types： Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion， followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage， fractional nasal nitric oxide （FnNO） level， and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide （FeNO） in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA， accompanied by pharyngeal itching， foreign body sensation in the throat， dry throat， shortness of breath， dry mouth， and allergic manifestations. The disease involves the lung， liver， spleen， and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome， Shixie Neiyun syndrome， Tanyin Zufei syndrome， and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Objective:To evaluate the efficacy of combined cricopharyngeal myotomy (CPM) and autologous fat injection laryngoplasty (AFIL) in the management of dysphagia secondary to glossopharyngeal and vagal nerve injury.Methods:This retrospective cohort study collected the clinical data of 18 patients with persistent dysphagia due to glossopharyngeal and vagus nerve injuries, who underwent concurrent cricopharyngeal myotomy (CPM) and autologous fat injection laryngoplasty (AFIL) at the Department of Otolaryngology, Peking Union Medical College Hospital, from January 2017 to December 2024. Pre-and postoperative assessments included electronic flexible laryngoscope, the Chinese version of Swallow Quality-of-Life Questionnaire (CSWAL-QOL), videofluoroscopic swallowing study (VFSS), body weight changes, and nasogastric tube (NGT) removal status with routine follow-up. The comparison of swallowing function before and after surgery was conducted using paired samples t-test and χ2 test. Results:The study cohort comprised 10 male and 8 female patients, with ages ranging from 33 to 70 years (mean±SD: 53.8±10.5). All surgical procedures were completed successfully without complications. During the 6-to 24-month follow-up period, 10 of the 13 patients who were initially nasogastric tube-dependent achieved successful decannulation. Compared with preoperative values, postoperative measurements demonstrated statistically significant improvements across all parameters: mean body weight increased from (56.95±9.14) kg to (59.22±8.72) kg ( t=3.689 , P<0.01), CSWAL-QOL scores improved from 91.89±17.81 to 130.83±25.42 ( t=6.921 , P<0.01), while, both VFSS scales showed marked reductions (VFSS-SWAL: 6.78±1.40 to 3.39±1.61, t=-8.001, P<0.01; PAS: 6.56±1.15 to 2.94±1.26, t=-10.114, P<0.01). Conclusions:Combined CPM and AFIL represents an effective surgical approach for dysphagia following glossopharyngeal and vagal nerve injury, thereby demonstrating significant improvements in both swallowing function and quality of life.