Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background The positive rate of work-related musculoskeletal disorders (WMSDs) among coal mine workers remains high, which seriously affects the quality of life of the workers. Objective To estimate the prevalence of WMSDs among coal miners in Shanxi Province and analyze their influencing factors. Methods From May to December 2023, 2315 coal miners from a coal mine enterprise inShanxi Province were selected by convenience sampling, and the self-administered Basic Situation Survey Scale, Musculoskeletal Disorders Questionnaire, Effort-Reward Imbalance Questionnaire, and Pittsburgh Sleep Quality Scale were used to evaluate general demographic characteristics, work organization characteristics, living habits, sleep quality, occupational stress, and occurrence of WMSDs symptoms and the corresponding absences (sickness absence) in past 1 year. The positive rate and absenteeism rate of WMSDs were caculated, and Pearson's chi-square test was used for identify influencing factors of WMSDs, and finally a binary logistic regression method was used to further studying the factors. Results A total of 2577 questionnaires were distributed in this survey, and 2315 valid questionnaires were recovered, with an effective recovery rate of 89.9%. The positive rate of WMSDs symptoms was 48.7% (1127/2315), the absenteeism rate due to WMSDs was 22.6% (523/2315), and the waist (17.5%), neck (11.7%), and knee (9.0%) were the most common areas presenting WMSDs symptoms. The results of logistic regression showed that compared with ≤10 years of service, the risk of WMSDs was higher for those with > 20 years of service (OR=2.167, 95%CI: 1.419, 3.311). Compared with the daily working time of ≤8 h, the risk of WMSDs was higher for those >8 h daily working time (OR=1.463, 95%CI: 1.211, 1.767). A higher risk of WMSDs was reported in workers with moderate labor intensity (OR=1.247, 95%CI: 1.009, 1.542) or heavy labor intensity (OR=1.570, 95%CI: 1.215, 2.027) than those with light labor intensity. The higher the education level (OR _{high school and technical secondary school}=1.866, 95%CI: 1.435, 2.425; OR _{junior college/bachelor degree or above}=1.953, 95%CI: 1.445, 2.639), the higher the risk of WMSDs. The risk of WMSDs was higher in workers reporting smoking (OR=1.225, 95%CI: 1.021, 1.470) or alcohol consumption (OR=1.345, 95%CI: 1.122, 1.612). The risk of WMSDs in coal miners with high occupational stress (OR=1.229, 95%CI:1.030, 1.466) or those with sleep disorders (OR=3.616, 95%CI:2.824, 4.629) was higher than that in workers with low occupational stress or no sleep disorders respectively. Conclusion The positive rate of WMSDs among coal mine personnel in Shanxi Province is high, and education level, length of service, daily working hours, smoking, alcohol consumption, labor intensity, sleep disorders, and occupational stress are influencing factors for WMSDs.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Background Thyroid hormones are crucial for development and proper functioning of human physiological systems. Current research on the thyroid mainly focuses on the impacts of lifestyle factors on thyroid dysfunction, while less attention is paid to the factors affecting thyroid hormone levels, especially occupational hazards, which warrants further investigation. Objective To investigate the associations between occupational hazard exposure and thyroid-stimulating hormone (TSH) and thyroid hormone levels in male coal mine workers. Methods A cross-sectional study design was adopted. A total of 12564 workers who participated in the occupational health check-ups at the Xishan Coal Electricity (Group) Corporation Occupational Disease Prevention and Control Institute in 2023 and met the inclusion and exclusion criteria were selected as research subjects. A self-designed electronic questionnaire was used to collect basic information, occupational history, and lifestyle habits of all study subjects. Height, weight, thyroid function test results, and occupational hazard exposure of the study subjects were obtained through occupational health examinations and routine workplace occupational hazard detection records. Generalized linear regression was used to analyze the associations between occupational hazard exposure and the levels of TSH and thyroid hormones. Results The median (P₂₅, P₇₅) levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and TSH in the included 12564 male coal mine workers were 1.16 (1.03, 1.29) ng·mL⁻¹, 7.70 (6.70, 8.90) μg·dL⁻¹, 3.63 (3.40, 3.84) pg·mL⁻¹, 1.19 (1.08, 1.30) ng·dL⁻¹, and 1.93 (1.36, 2.78) μIU·mL⁻¹, respectively. The overall abnormality rate of thyroid hormones was 2.83%, with the highest rate for subclinical hypothyroidism (1.83%), followed by hyperthyroidism (0.37%), hypothyroidism (0.32%), and subclinical hyperthyroidism (0.31%). After adjustment for confounding factors, the generalized linear regression model showed that long working hours were associated with higher levels of T3 and FT3, with β (95%CI) values of 0.011 (0.003, 0.019) and 0.038 (0.019, 0.057) respectively. Night shift work was linked to increased TSH levels and decreased FT4 levels, with β (95%CI) values of 0.171 (0.016, 0.326) and −0.012 (−0.019, −0.006) respectively. Coal dust exposure was associated with decreased levels of T3 and T4, with β (95%CI) values of −0.022 (−0.037, −0.008) and −0.320 (−0.434, −0.207) respectively. Noise exposure was related to decreased levels of T4 and FT4, with β (95%CI) values of −0.102 (−0.166, −0.038) and −0.020 (−0.027, −0.013) respectively. Conclusion The TSH and thyroid hormone levels of coal miners are mostly within the normal reference ranges, with a low abnormality rate. Long work hours, night shift work, coal dust, and noise are associated with the levels of TSH and thyroid hormone levels in the male miners. Coal companies should reasonably arrange working hours, optimize the night shift scheduling system, and enhance protection against coal dust and noise to promote occupational health and safeguard the physical health of miners.

ObjectiveTo investigate the accuracy of multiple discriminant analysis （MDA） versus fibrosis-4 （FIB-4） in assessing liver fibrosis degree in patients with HBV infection， as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included， and their clinical data were collected. According to the results of pathological examination， they were divided into non-significant fibrosis group （F<2） with 126 patients and significant fibrosis group （F≥2） with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed， and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up， and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit， they were divided into progressive group with 21 patients and non-progressive group with 41 patients； the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up， and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic （ROC） curve was used to investigate the diagnostic efficacy of indicators， the Z-test was used for comparison of the area under the ROC curve （AUC）， and the paired chi-square test was used for comparison of the sensitivity， specificity， and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378， while the correlation coefficient between MDA and liver fibrosis degree was -0.325 （both P<0.001）. FIB-4 had an AUC of 0.688， a sensitivity of 64.96%， a specificity of 68.87%， a positive predictive value of 67.42%， a negative predictive value of 63.36%， an accuracy of 65.40%， and a cut-off value of 1.01， while MDA had an AUC of 0.653， a sensitivity of 52.55%， a specificity of 78.57%， a positive predictive value of 72.73%， a negative predictive value of 60.37%， an accuracy of 65.02%， and a cut-off value of 0.29， suggesting that compared with FIB-4， MDA had a lower sensitivity （P=0.004） and a higher specificity （P=0.001）. The progressive group had a significantly higher age than the non-progressive group at baseline （t=2.611， P=0.011）. For the progressive group， there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up （both P<0.001）， while the non-progressive group showed no significant changes （both P>0.05）. The multivariate Logistic regression analysis showed that aspartate aminotransferase （odds ratio ［OR］=0.940， 95% confidence interval ［CI］： 0.885‍ ‍—‍ ‍0.998， P<0.05） and MDA （OR=0.445， 95%CI： 0.279‍ ‍—‍ ‍0.710， P<0.001） were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis， and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis， which can help to reduce the need for liver biopsy in clinical practice.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Giant cell tumor of bone (GCTB) is a common locally aggressive junctional primary bone tumor, whose clinical treatment becomes more difficult once combined with pathological fracture. Extended curettage and en-bloc resection are common surgical procedures for treating GCTB, and drugs such as receptor activator of nuclear factor-κB ligand(RANKL) inhibitors and bisphosphonates have been successfully used. Curettage is recommended for patients with Campanaccigrade Ⅱor Campanaccigrade Ⅲ with localized soft tissue invasion only and simple fractures with intact bone structure. Resection may be considered for Campanaccigrade Ⅲ with extensive soft tissue invasion or complex fractures with incomplete bone structure. RANKL inhibitors such as denosumab may be recommended if surgery is not possible or before performing resection. This article summarizes the common treatment modalities of pathological fractures combined with giant cell tumors of extremities, including the current status of surgical and pharmacological treatments, analyzing the choice of surgical modalities in different clinical situations, in order to provide clinical inspirations for diagnosis and treatment.

Giant cell tumor of bone (GCTB) is a common locally aggressive junctional primary bone tumor, whose clinical treatment becomes more difficult once combined with pathological fracture. Extended curettage and en-bloc resection are common surgical procedures for treating GCTB, and drugs such as receptor activator of nuclear factor-κB ligand(RANKL) inhibitors and bisphosphonates have been successfully used. Curettage is recommended for patients with Campanaccigrade Ⅱor Campanaccigrade Ⅲ with localized soft tissue invasion only and simple fractures with intact bone structure. Resection may be considered for Campanaccigrade Ⅲ with extensive soft tissue invasion or complex fractures with incomplete bone structure. RANKL inhibitors such as denosumab may be recommended if surgery is not possible or before performing resection. This article summarizes the common treatment modalities of pathological fractures combined with giant cell tumors of extremities, including the current status of surgical and pharmacological treatments, analyzing the choice of surgical modalities in different clinical situations, in order to provide clinical inspirations for diagnosis and treatment.

ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.

To systematically review randomized controlled trials （RCTs） of traditional Chinese medicine （TCM） intervention in ulcerative colitis （UC）， and analyze the characteristics of these studies and their outcome indicators， thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， SinoMed， PubMed， Cochrane Library， EMbase， and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed， and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included， with a sample size of 44 853 participants. The largest sample size was 218 cases， and the smallest was 28 cases， with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types， the top three were large intestine dampness-heat syndrome （31.05%）， spleen and kidney yang deficiency syndrome （12.47%）， and spleen deficiency with dampness syndrome （9.17%）. The interventions， ranked by frequency of use， included internal Chinese medicine compounds/preparations （64.5%）， Chinese medicine compounds/preparations with retained enema （18.2%）， internal Chinese medicine compounds/preparations + external TCM treatment （5.95%）， and external TCM treatment alone （4.86%）. The treatment duration was mainly 4-8 weeks （64.86%）， with 61 studies （10.99%） reporting follow-up time. A total of 157 outcome indicators were used， with a frequency of 3 460 occurrences， classified into six domains： TCM syndromes and symptoms （346 occurrences， 10%）， symptoms/signs （541 occurrences， 15.64%）， physical and chemical examinations （2 119 occurrences， 61.24%）， quality of life （107 occurrences， 3.09%）， long-term prognosis （61 occurrences， 1.76%）， and safety events （284 occurrences， 8.21%）. The analysis reveals several limitations in the outcome indicators of TCM intervention in UC， including the lack of a basis for sample size calculation， non-standardized TCM syndrome classification， absence of trial design and registration， inadequate blinding and allocation concealment， adherence issues with interventions， imbalanced selection of surrogate and endpoint indicators， inconsistency in the timing of outcome measurements， design issues that require standardization， and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification， clear efficacy evaluation indicators， key endpoint indicators， and reasonable measurement time points. Long-term prognostic impacts， comprehensive assessments of patients' quality of life， and consideration of economic benefits should be emphasized， providing a basis for the clinical practice of TCM in the treatment of UC.