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 understand the current status of traditional Chinese medicine(TCM)systematic reviews/Meta-analysis over the past 10 years.Methods Cochrane Database of Systematic Reviews,PubMed,Web of Knowledge,CNKI,SinoMed,WanFang Data,VIP databases,as well as the Cochrane Register and PROSPERO registration platform were searched to collect TCM-related systematic reviews/Meta-analysis published between January 2015 and December 2024.Literature was screened,and standardization of institutions,countries,and journals was performed.Data cleaning was conducted,and trends in publication years,high-frequency diseases,journals,institutions,and highly cited papers were analyzed.Results A total of 11,174 papers were included,involving approximately 56,656 authors from 1,422 institutions across 44 countries,covering 1,300 journals and 1,070 diseases.The top five institutions in terms of publications were Beijing University of Chinese Medicine(954 papers),Guangzhou University of Chinese Medicine(928 papers),China Academy of Chinese Medical Sciences(537 papers),Tianjin University of Chinese Medicine(460 papers),and Chengdu University of Chinese Medicine(393 papers).Foreign institutions with the highest publication volumes were concentrated in South Korea,Iran,and Australia.The most frequently published Chinese journal was Zhongyi Clinical Research with 332 papers,while the most published English journal was Evidence-Based Complementary and Alternative Medicine with 311 papers.There were 282 single-author papers involving 271 authors,and the most cited paper was referenced 323 times,The three most frequently studied diseases were diabetes(267 papers,2.39％),angina pectoris(214 papers,1.92％),and osteoarthritis(210 papers,1.88％).Non-pharmacological interventions such as acupuncture(1,265 papers,11.32％),auricular therapy(101 papers,0.90％),and Tai Chi(98 papers,0.88％)were most frequently reported.In pharmacological interventions,studies on Tripterygium wilfordii tablets(76 papers,0.68％)and Danhong injection(54 papers,0.48％)were more common.Conclusion The systematic reviews/Meta-analysis method is widely used in the field of TCM,and the field continues to grow.Active academic teams,institutions,and journals have emerged.Over the past decade,there has been a considerable body of evidence in Chinese systematic reviews on TCM for chronic diseases such as diabetes,angina pectoris,and osteoarthritis.In English-language studies,non-pharmacological therapies like acupuncture have been more widely reported,and some high-impact studies have emerged.However,challenges remain,such as issues with research transparency and methodological standardization.Future efforts should focus on establishing transparent systems and quality control mechanisms to further enhance the reliability,accuracy,and dissemination of TCM evidence-based research.

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.

OBJECTIVE To comparatively analyze tumor staging versus clinical staging in reimbursement scope restrictions under medical insurance for antineoplastic agents in order to better implement the medicare drug payment policy. METHODS Antineoplastic agents included in the National Basic Medical Insurance， Workers’ Compensation Insurance and Maternity Insurance Drug Catalogue （2024） （hereinafter referred to as the “Medical Insurance Catalog”） were used as research subject to compile and analyze reimbursement scope restrictions regarding tumor staging. By consulting clinical diagnosis and treatment guidelines and relevant literature， the tumor staging in reimbursement scope restrictions of the Medical Insurance Catalog was mapped and compared with clinical staging. RESULTS & CONCLUSIONS A total of 89 antineoplastic agents’ medical insurance payments had tumor staging. Among these， there were 86 western drugs （including 17 ordinary western drugs， 68 negotiated drugs， and 1 competitive drug） and 3 Chinese patent medicines （including 1 ordinary Chinese patent medicine and 2 negotiated drugs）. Non-small cell lung cancer involved the most restricted payment drugs， with 36 drugs. The tumor staging in reimbursement scope restrictions was mostly “metastatic” and “locally advanced”， involving 67 and 48 drugs respectively. Tumor staging in most reimbursement scope restrictions could correspond to the clinical staging of the tumor. However， mid-advanced esophageal cancer， unresectable gastrointestinal stromal tumors， unresectable locally advanced neuroendocrine tumors， locally advanced basal cell carcinoma， and unresectable neurofibromatosis type Ⅰ did not have a corresponding clinical staging mentioned in authoritative guidelines or high-quality clinical studies and need to be determined by the clinic according to the actual situation of the patient. Therefore， it is recommended that the interpretation of tumor staging in reimbursement scope restrictions should be accurately defined and standardized， so as to improve the accuracy of the drug payment policy in the actual implementation process.

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.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Objective To investigate whether ginsenoside Rh1(G-Rh1)can alleviate liver fibrosis induced by a choline-deficient,L-amino acid-defined,high-fat diet(CDAHFD)and to explore its underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into 6 groups(n=8 in each group),including a standard diet group(or the control group),a high-fat diet group(or the CDAHFD group),a silymarin group(given silymarin at 5 mg/kg),a low-dose G-Rh1 group(given G-Rh1at 5 mg/kg),a medium-dose G-Rh1 group(given G-Rh1at 10 mg/kg),and a high-dose G-Rh1 group(given G-Rh1 at 20 mg/kg).The control group was given a standard feed,while the other groups were fed CDAHFD for 7 weeks to establish the mouse model of liver fibrosis.Starting from the first week,the mice in the treatment groups were administered the corresponding drugs by intragastric gavage once daily for 7 weeks in succession.After the administration of the final drug treatment,the body mass and organ mass of the mice in different groups were measured,and the organ index was obtained according.Liver tissues were examined using HE staining,Sirius red staining,and immunohistochemistry(IHC)staining.Western blot was performed to measure α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1),two liver fibrosis-related proteins,and fibroblast growth factor 12(FGF-12),a pathway-related protein.The serum biochemical indicators,including aspartate transferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Additionally,RAW246.7 cells were randomly divided into 5 groups,including a control group,a lipopolysaccharide(LPS)group,and 3 G-Rh1 treatment groups.The control group had only RAW246.7 cells in the culture medium.The other groups were given LPS(500 ng/mL),and the 3 treatment groups received G-Rh1 at 10,20,and 40 μmol/L in addition.The supernatants from the 5 groups of RAW246.7 cells were collected and cocultured with HSC-T6 cells for 24 hours to observe and compare the effects of G-Rh1 and LPS on the expression of fibrosis-related proteins,including α-SMA,Col1a1,etc,in HSC-T6 cells and on the expression of fibrotic signaling pathway-related proteins,including fibroblast growth factor 12(FGF-12)and signal transducer and activator of transcription 3(STAT3)/phosphorylated STAT3(p-STAT3),in RAW264.7 cells.Flow cytometry was conducted to analyze the phenotypes of RAW246.7 cells,and ELISA was performed to measure fibrosis-related factors,including monocyte chemoattractant protein-1(MCP-1)and transforming growth factor-β(TGF-β).Results Compared with the control mice,the mice in the CDAHFD group exhibited obvious liver fibrosis.Compared with CDAHFD mice,mice in the G-Rh1 treatment groups all showed alleviation of liver fibrosis of was alleviated to some extent in a dose-dependent manner,and the improvement effect was superior to that of silymarin,a reference drug.G-Rh1 also alleviated CDAHFD-induced body mass loss(P＜0.01),reduced the liver index(P＜0.01),and significantly decreased the serum levels of AST,ALT,DBIL,and TBIL(P＜0.0001).Significant differences in the protein expression ofα-SMA,TGF-β1,and FGF-12 in the liver were observed(P＜0.01).Compared with the LPS group,the LPS+G-Rh,groups exhibited significant differences in the expression of FGF-12 and p-STAT3/STAT3 in RAW246.7 cells,and α-SMA and Col1a1 in HSC-T6 cells(P＜0.001).In the LPS+G-Rh,groups(the 20 μmol/L and 40 μmol/L treatment groups),the conversion ratio of Ly6C-low expressing RAW246.7 cells into Ly6C-high expressing RAW246.7 cells decreased significantly(P＜0.0001),while the secretion of fibrosis-related factors MCP-1 and TGF-β decreased(P＜0.0001),which was consistent with the trend of the activation levels of HSC-T6 cells.Conclusions G-Rh1 can prevent and improve CDAHFD-induced liver fibrosis in mice,potentially through mechanisms involving the reduction of RAW264.7 phenotype transformation mediated by FGF-12 overexpression.

Objective To understand the current status of traditional Chinese medicine(TCM)systematic reviews/Meta-analysis over the past 10 years.Methods Cochrane Database of Systematic Reviews,PubMed,Web of Knowledge,CNKI,SinoMed,WanFang Data,VIP databases,as well as the Cochrane Register and PROSPERO registration platform were searched to collect TCM-related systematic reviews/Meta-analysis published between January 2015 and December 2024.Literature was screened,and standardization of institutions,countries,and journals was performed.Data cleaning was conducted,and trends in publication years,high-frequency diseases,journals,institutions,and highly cited papers were analyzed.Results A total of 11,174 papers were included,involving approximately 56,656 authors from 1,422 institutions across 44 countries,covering 1,300 journals and 1,070 diseases.The top five institutions in terms of publications were Beijing University of Chinese Medicine(954 papers),Guangzhou University of Chinese Medicine(928 papers),China Academy of Chinese Medical Sciences(537 papers),Tianjin University of Chinese Medicine(460 papers),and Chengdu University of Chinese Medicine(393 papers).Foreign institutions with the highest publication volumes were concentrated in South Korea,Iran,and Australia.The most frequently published Chinese journal was Zhongyi Clinical Research with 332 papers,while the most published English journal was Evidence-Based Complementary and Alternative Medicine with 311 papers.There were 282 single-author papers involving 271 authors,and the most cited paper was referenced 323 times,The three most frequently studied diseases were diabetes(267 papers,2.39％),angina pectoris(214 papers,1.92％),and osteoarthritis(210 papers,1.88％).Non-pharmacological interventions such as acupuncture(1,265 papers,11.32％),auricular therapy(101 papers,0.90％),and Tai Chi(98 papers,0.88％)were most frequently reported.In pharmacological interventions,studies on Tripterygium wilfordii tablets(76 papers,0.68％)and Danhong injection(54 papers,0.48％)were more common.Conclusion The systematic reviews/Meta-analysis method is widely used in the field of TCM,and the field continues to grow.Active academic teams,institutions,and journals have emerged.Over the past decade,there has been a considerable body of evidence in Chinese systematic reviews on TCM for chronic diseases such as diabetes,angina pectoris,and osteoarthritis.In English-language studies,non-pharmacological therapies like acupuncture have been more widely reported,and some high-impact studies have emerged.However,challenges remain,such as issues with research transparency and methodological standardization.Future efforts should focus on establishing transparent systems and quality control mechanisms to further enhance the reliability,accuracy,and dissemination of TCM evidence-based research.

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.