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.

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

The pathogenesis of male infertility is intricate and complex,and now,Western medicine is primarily based on empirical drug treatment.Male infertility is one of the advantageous diseases of traditional Chinese medicine,and traditional Chinese medicine has obvious effect in improving male reproductive function,which is one of the important means of clinical treatment of this disease.Based on the classical ancient books and modern research,and based on the traditional tonifying kidney method,we have innovatively put forward the concept of treating male infertility with the principle of"deficiency of kidney essence as the root,tonifying kidney and benefiting essence as the method,and regulating yin and yang mildly as the rule",which has achieved good clinical efficacy.At the same time,combined with the long-term clinical practice of our team,we have proposed five major diagnosis and treatment strategies for male infertility,i.e.,combining disease identification with syndrome identification,combining macroscopic with microscopic approaches,combining holistic with localized treatments,combining traditional Chinese medicine with surgery,and combining treatment of the disease and treatment of the person.In addition,we have summarized some of the current problems in the treatment of male infertility with traditional Chinese medicine and put forward corresponding suggestions,with a view to promoting the development and application of traditional Chinese medicine in the treatment of male infertility.

Talents are the main force for the development of traditional Chinese medicine（TCM）， and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present， we are still exploring and developing in the fields of the formulation， implementation and evaluation indicators of TCM talent evaluation system. However， there are shortcomings and difficulties. For instance， insufficient stratification in the evaluation， excessive emphasis on the quantity of achievements， neglecting the quality of the achievements and the actual contribution， imperfect assessment indicators， and the weak characteristics of TCM. Therefore， national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard， in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value， ability and contribution. For the evaluation of TCM clinical talents， China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM（CCCL-TCM）， which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry， and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.

The pathogenesis of varicocele infertility is complex, and currently, there is no specific drug for clinical treatment, traditional Chinese medicine (TCM) has certain advantages in improving clinical symptoms of patients and improving sperm quality. Based on the theory of deficiency and stasis in TCM and modern related research, we believe that static blood blocking collaterals is the initiating factor of this disease, and kidney essence deficiency is the immanent trend of this disease. The pathogenesis and treatment method of this disease are studied on the basis of "soil theory". Guilu Tongqu Decoction is a formula developed by our team based on "soil theory" for the treatment of varicocele infertility. It is a modified version of the classic formula Zuogui Pill , which has the effects of tonifying the kidney, nourishing essence, and promoting blood circulation for removing blood stasis. Its clinical efficacy is good. At the same time, based on our team's extensive clinical practice, we propose three treatment strategies for varicocele infertility, namely, the combination of systemic and local treatment, the combination of radial and symptomatic treatment, and the combination of TCM and surgical procedures. These methods can effectively improve the overall therapeutic effect and provide a reference for the treatment of varicocele infertility with TCM.

OBJECTIVE To analyze the difference between the payment limitations of anti-cancer drugs and application scope of drug instructions， so as to better implement the payment policy of medical insurance drugs. METHODS The differences between the payment limitations of anti-cancer drugs and application scope of drug instructions in the National Catalogue of Drugs for Basic Medical Insurance， Industrial Injury Insurance and Maternity Insurance （2022） were compared and analyzed； the evidence-based basis of the difference was discussed， and the scope of limited payment was interpreted. RESULTS Totally 118 drugs had payment limitations； limitations scope mainly included limited evidence of gene detection results， limited indications， limited second-line and above treatment， limited payment duration， limited specialist prescription， limited medical institution grade， etc. Among them， 43 drugs had differences between the payment limitations and drug instructions， and the indications of 31 drugs were greater than payment limitations； for seven drugs， the drug indications beyond the payment limitations were recommended by the guidelines. The payment limitations of 75 drugs were consistent with drug instructions. The second-line and multi-line treatment was ineffective or intolerable with first-line drugs. There was a certain relationship between locally advanced， advanced or metastatic tumor and tumor stage， but different tumors had different criteria. Systemic treatment mainly referred to systemic treatment with drug. The results of limited genetic test required that the result was positive or negative. In addition， six kinds of TCM injections were limited to the level of medical institutions； the payment of two drugs did not exceed 12 months； when lenalidomide was combined with isazomide citrate， the medical insurance only paid for one of the drugs. CONCLUSIONS The payment limitations of some anti- cancer drugs are inconsistent with the drug indications. The drug payment limitations should be expanded according to the actual situation of clinical medication and the recommendations of guidelines. At the same time， the payment limitations should be formulated accurately and in detail， thus clinical and medical insurance staff can understand it and fully protect the interests of patients.

Objective:To investigate various clinical treatment measures for thoracolumbar fractures and provide new diagnosis and treatment methods.Methods:The case data of 5 patients(3 males, 2 females, and the age ranged from 39 to 59 years with an average of 51 years) with thoracolumbar fractures were treated with Waveflex semi-rigid internaI fixation system from May 2020 to December 2021 were retrospectively analyzed, imaging indexes and clinical effects were followed up, and analyzed and summarized in combination with relevant literatures.Results:The operations of all 5 patients were successfully completed, and the follow-up period was 6 months. At the last follow-up, the internal fixation position was good, the height of the injured vertebra was maintained satisfactorily, and the clinical effect was satisfactory.Conclusion:Waveflex semi-rigid internal fixation system combines the advantages of fusion and non-fusion, providing a new idea for the treatment of thoracolumbar fractures, but its long-term effect still needs further follow-up.

Objective:To investigate the clinical and genetic characteristics of families with myotonic dystrophy type I.Methods:Two families with myotonic dystrophy type I admitted to Department of Neurology, First Affiliated Hospital of He'nan University of Science and Technology in September and October 2021 were chosen; their clinical data were retrospectively analyzed. The muscle pathological changes were confirmed by electromyography and muscle MRI. Repeat-primed PCR assay was used to detect the number of CTG repeats in the 3' end non-coding region of DMPK gene. Results:Clinical heterogeneity existed among the two families of patients; muscle weakness and muscular atrophy of the skeletal muscle were the main clinical manifestations; limb weakness, axe face, percussion myotonia and myoglobular sign were noted; systemic multi-system symptoms included palpitation and chest tightness, cataracts, gastrointestinal symptoms, fatigue/lethargy, and cognitive impairment. Electromyography showed myotonic potential and myogenic damage. Muscle fatty infiltration and atrophy were noted in muscle MRI, and lesions were predominantly in the gastrocnemius. All patients had abnormal amplification of DMPK gene CTG (number of CTG repeats> 50 or 100). Conclusion:In addition to skeletal muscle involvement, systemic multi-system involvement such as cardiac, eye, respiratory, endocrine, and nervous system should also be noted by clinicians in patients with myotonic dystrophy type I.

OBJECTIVE To evaluate the effectiveness and safety of trastuzumab biosimilars and original drugs in the treatment of human epidermal growth factor receptor -2（HER-2）positive breast cancer systematically ，and to provide evidence -based basis for the selection of clinical treatment . METHODS Retrieved from PubMed ，Embase，Web of Science ，Cochrane Library ，CNKI， CBM，VIP，Wanfang database ，ClinicalTrials and Clinical Trial Center of China ，randomized controlled trials （RCTs）about trastuzumab biosimilars （trial group ）versus original drugs （control group ）in the treatment of HER -2 positive breast cancer were collected. After data extraction and quality evaluation ，RevMan 5.4 statistical software was used for meta -analysis. RESULTS Totally 11 RCTs were enrolled ，involving 5 812 patients. Results of meta -analysis showed that there was no significant difference in objective response rate （based on whether intention -to-treat population nor per -protocol population ），pathologic complete response ， proportion of progression free survival population ，proportion of overall survival population ，anti-drug antibody positive rate ， neutralizing antibody positive rate ，and incidence of adverse drug reactions between 2 groups（P＞0.05）. CONCLUSIONS The effectiveness and safety of trastuzumab biosimilars are equivalent to those of trastuzumab original drugs .