BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

Objective To explore the value of CT signs and quantitative parameters of artificial intelligence (AI) in predicting the efficacy of neoadjuvant chemotherapy for colorectal cancer. Methods A total of 349 colorectal cancer patients who received neoadjuvant chemotherapy at Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province from January 2022 to January 2025 were selected and and divided into the effective group (n = 267) and the ineffective group (n = 82) according to the evaluation criteria for the efficacy of solid tumors. Conduct a CT examination and extract AI quantitative parameters from the CT images based on the lesion. The data were analyzed using SPSS21.0 software, Logistic regression was used to screen the influencing factors of ineffective neoadjuvant chemotherapy in patients with colorectal cancer, and separate and combined models of CT signs and AI quantitative parameters were established. The predictive effect of the model was verified by using the ROC curve, calibration curve and decision curve. Results Compared with the effective group, the proportion of regular tumor morphology and the proportion of non-enlarged lymph nodesin the ineffective group were smaller. The tumor volume, peak value and entropy value were larger (P < 0.05). Multivariable analysis showed that irregular shape (OR= 4.216), presence of lymph node enlargement (OR = 8.998), larger tumor volume (OR = 1.109), higher average CT value (OR = 1.120), elevated peak value (OR = 2.528), and increased entropy value (OR = 1.390) were independent risk factors for ineffective neoadjuvant chemotherapy in colorectal cancer (P < 0.05). The areas under the ROC curves of the individual and combined models of CT signs and AI quantitative parameters were 0.777, 0.818, and 0.877, respectively(P < 0.05). The calibration curve showed a Brier score of 0.091. The decision curve showed that the threshold was between 0.10 and 0.85, and the combined model achieved a relatively high net clinical benefit. Conclusion CT signs combined with AI quantitative parameters has a predictive value for the efficacy of neoadjuvant chemotherapy in colorectal cancer. To provide evidence-based basis for clinical screening of the population benefiting from chemotherapy and optimization of treatment strategies.

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

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*

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.

Objective To investigate the feasibility of using Cariostat test for caries risk assessment in adult outpatients and provide a reference basis for caries prevention and treatment in adult outpatients of different ages.Methods Fifty-two adult patients of different ages(18-24,25-34,35-44,45-54,and≥55 years old)attending outpatient clinics of The Affiliated Stomatological Hospital of Nanjing Medical University were tested for caries activity using the Cariostat test.Oral examinations were conducted according to the criteria of the 5th edition of the Basic Methods of Oral Health Surveys of the World Health Organization,and on-site questionnaire sur-veys were performed for the Cariogram assessment system.Oral examinations included assessments of dental arch conditions and caries status,while questionnaire surveys covered dietary habits,oral health care habits,etc.The caries status of adult outpatients of different age groups was analyzed,and caries activity was assessed using the Cariostat test.The caries risk levels were determined,and the con-sistency between the Cariostat test and the Cariogram assessment system was evaluated.Results It was found that there was a differ-ence in mean decayed,missing and filled surfaces(DMFS)between the low-risk group of adult outpatients with different caries risk levels classed by the Cariostat test and the intermediate and high-risk groups(P＜0.05).There was a difference in mean decayed,missing and filled teeth(DMFT)and mean DMFS between the low-risk group of adult outpatients with different caries risk levels classed by Cariogram and the intermediate and high-risk groups(P＜0.05).The evaluation results of caries risk levels in adult outpa-tients classed by the Cariostat test and the Cariogram assessment system showed a Kappa value of 0.467(P＜0.05)in the≥55 years old group,indicating moderate consistency.Conclusion The Cariostat test is useful in understanding the caries activity of adult outpa-tients and is particularly accurate and effective in patients at the age of 55 or older.

Ion mobility spectroscopy(IMS)has many advantages such as fast detection speed,high sensitivity,and portability,and thus plays an important role in on-site detection of chemical agents,explosives,drugs,environmental pollutants,and other pollutants.As a key component of IMS,the ion number density and temporal width of the injected ion packets directly determine the IMS detection sensitivity and resolution.In yhis study,the dual-parallel-grid structure of Tyndall-Powell gate(TPG),which could effectively isolate the electric fields within the ionization region,gate region,and drift region,was utilized to develop a dual effect TPG gating method for simultaneously enhancing the mobility discrimination reduction and ion packet temporal width compression,thereby improving the IMS performance.A TPG-IMS platform was thus built up and the effects of parameters such as gate opening pulsed width,gate penetration voltage,and ion injection voltage on the sensitivity and resolving power of IMS were systematically investigated using the dual-effect TPG gating method.The results demonstrated that,when detecting diethyl phosphate(DEP)and diethyl methylphosphate(DEMP)mixture using the dual effect TPG gating method,the peak currents of(DEP)2H+and(DEP·DEMP)H+ions with low K0 values were increased by 18 and 45 times respectively,while maintaining a high resolution of about 90.The limits of detection for DEP and DEMP were decreased from 4 ppb(10-9)to 235 ppt(10-12)and from 5 ppb to 156 ppt,respectively.This gating method only regulated the potential of the TPG grid adjacent to the drift region,without changing the structure of the ion mobility tube,making it convenient to apply on existing commercial instruments.

Objective To investigate the relationship between serum chemokine C-X-C-motif ligand 16(CXCL16),CC chemokine ligand 20(CCL20)and inflammatory factors and mucosal healing in patients with ulcerative colitis(UC).Methods A total of 170 UC patients admitted to Chengdu Shuangliu District First People's Hospital/West China Airport Hospital of Sichuan University from January 2021 to October 2022 were selected as the study group,and 100 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.The levels of serum CXCL16,CCL20 and inflamma-tory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-17(IL-17),tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in the two groups were compared.The correlation between serum CX-CL16,CCL20 and inflammatory factors in UC patients was analyzed.According to the prognosis of mucosal healing after treatment,UC patients were divided into good healing group and poor healing group.Serum CX-CL16 and CCL20 levels of patients with different prognosis were compared.Univariate and multivariate Logis-tic regression analysis models were used to analyze the risk factors of poor mucosal healing in UC patients af-ter treatment,and the predictive value of serum CXCL16 and CCL20 in poor mucosal healing in UC patients after treatment was analyzed by receiver operating characteristic(ROC)curve.Results The levels of serum CXCL16,CCL20,IL-1β,IL-6,TNF-α,IL-17 and CRP in the study group were significantly higher than those in the control group,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum CX-CL16 and CCL20 were positively correlated with IL-1β,IL-6,TNF-α,IL-17 and CRP in UC patients,respec-tively(P＜0.05),and serum CXCL16 was positively correlated with CCL20(P＜0.05).The levels of CX-CL16 and CCL20 in poor healing group were significantly higher than those in good healing group,and the difference was statistically significant(P＜0.05).Multifactor Logistic regression analysis showed that in-creased CXCL16 level,CCL20 level,drinking history,severity of disease classification,erythrocyte sedimenta-tion rate(ESR)level and CRP level were risk factors for poor mucosal healing in UC patients after treatment(P＜0.05).ROC curve results showed that the combined detection of serum CXCL16 and CCL20 predicted a larger area under the curve(AUC)for poor mucosal healing after treatment in UC patients,and the combined detection of serum CXCL16 and CCL20 with ESR and CRP predicted the largest AUC for poor mucosal heal-ing after treatment in UC patients.Conclusion The serum levels of CXCL16 and CCL20 in UC patients are closely related to inflammatory factors,and the combined detection have high predictive value for poor muco-sal healing in UC patients after treatment.