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.

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.

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*

ObjectiveTo construct a macro-evaluation tool for dampness syndrome （DS） animal model， which will provide a basis for experimental research on dampness syndrome in traditional Chinese medicine （TCM）. MethodsConceptual framework of this study was clarified through discussions within the core working group， and dimensions of the evaluation of the animal model of DS were identified according to TCM principles. We searched CNKI， Wanfang， VIP and SinoMed databases from the inception to June 30th， 2023， on experiments involving dampness syndrome animals to create a pool of items about DS animal models. The core items were selected and extracted for factor analysis and cluster analysis. An expert importance rating questionnaire was developed based on the results of the literature review， analyzing the distribution of item scores， importance averages， and coefficient of variation. Through a comprehensive analysis of literature， expert importance scoring， and specific expert opinions， items that did not meet anyone of the criteria of average importance rating ≥2.04， coefficient of variation ≤30%， or literature eva-luation frequency ≥2% were removed， thereafter， the macro-evaluation tool for DS animal model was preliminarily constructed. ResultsSpirit and body state， autonomic activity state， body surface characteristics， diet， urination and defecation， tongue manifestation， and motor behavior assessment were constructed as the seven dimensions in the evaluation of DS animal model. A total of 348 papers about animal experiments were included and analyzed， resulting in a saturated pool of 72 items， which was refined to 38 core items of DS animal models. Factor analysis obtained 16 common factors， which were further clustered into two categories， named dampness transforming from heat syndrome and dampness transforming from cold syndrome. The expert importance scoring showed that the Kendall harmony coefficient was 0.359 （P＜0.05） indicating a high level of agreement， coordination and reliability among the experts. Notably， 50% or more of the experts considered the items thick and greasy tongue coating， unclean perianal area， loose stools， lethargy， unformed stools， and listless expression as very important. The median scores for all items were 2.04（1.73， 2.37）， with a coefficient of variation ranging from 19.73% to 53.38%. After expert evaluation， the macro-evaluation tool for DS animal model in TCM with 33 items and corresponding criteria for assessing the formation of DS models was finally contructed. ConclusionThe Macro-evaluation tool for DS animal model in TCM is highly scientific， credible， and operable， and can be utilized in DS animal experiments after its characteristics are actually evaluated.

OBJECTIVE To investigate the effect of the medical intelligent dispensing machine in the dispensing of pharmacy intravenous admixture services（PIVAS） parenteral nutrition drugs. METHODS From December 1st to 31st， 2023， 14 PIVAS staff members in Shandong Provincial Hospital Affiliated to Shandong First Medical University were selected to participate in manual dispensing and dispensing with the medical intelligent dispensing machine in the form of rotation. Ten prescribed formulas are prepared daily by each of the two groups. The dispensing efficiency and quality of specified parenteral nutrition drugs were compared between 2 groups， and the effects of the introduction of medical intelligent dispensing machine on the cleanliness class were also compared. RESULTS The medical intelligent dispensing machine group prepared a total of 310 bags of parenteral nutrition solution， while the manual dispensing group prepared a total of 306 bags； the time for drug dispensing per bag， the residual amount of drug liquid， the number of dispensing punctures， the leakage rate of finished infusion inlet and desquamation rate of vial glue plug in the medical intelligent dispensing machine group were less or lower than manual dispensing group （P＜ 0.05）. Before and after the introduction of the medical intelligent dispensing machine， the qualified rate of sedimentation bacteria detection in mixing operation room and horizontal laminar flow clean workbench in both groups was 100%. CONCLUSIONS The application of medical intelligent dispensing machine in the dispensing of PIVAS parenteral nutrition drugs can improve the efficiency of drug dispensing and improve the quality of finished infusion without affecting the cleanliness level of operation room and horizontal laminar flow clean workbench.

A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.

Fever of unknown origin(FUO)is a difficulty in clinical diagnosis and treatment.Patients with FUO come to seek medical consultation usually with fever as the main complaint,and the accompanying symptoms and signs are generally atypical.The pathogenesis of FUO remains conflicting in the field of modern western medicine,and its treatment is still focused on empirical anti-inflammatory management,which has the deficiency of delayed diagnosis,limited therapeutic options,poor therapeutic effects,and obvious adverse reactions.In the field of traditional Chinese medicine(TCM),FUO generally results from the dysfunction of zang-fu organs and the imbalance of yin and yang,and has the clinical features of long duration of illness,unknown etiology,complexity of illness,recurrent attacks,and difficult to be cured.Based on the six-meridian syndrome differentiation,Chief Physician LI Chuang-Peng pointed out that the pathogenesis of FUO is characterized by the combined disease of shaoyin and yangming,and put forward the therapeutic principle of warming shaoyin and unblocking yangming.He proposed the use of Dahuang Fuzi Decoction(mainly composed of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata)plus Yiyi Fuzi Baijiang Powder(mainly composed of Coicis Semen,Aconiti Lateralis Radix Praeparata and Patriniae Herba)to subside fever and eliminate pathogen,together with Asari Radix et Rhizoma for guiding the medicine directly to the shaoyin.Moreover,therapies of strengthening and activating spleen and stomach,nourishing yin to produce fluid,and unblocking the blood vessels can be used for eliminating the pathogen and supporting the healthy qi.