Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To study the activity of ten kinds of antipyretic-antidotal traditional Chinese medicine(TCM),including radix tinosporae.herb of blin conyza and turmeric,against extensively drug-resistant Acineto-bacter baumannii(XDR-AB)infection,screen out the extracts of antipyretic-antidotal TCM which have in vivo anti-infection activity,provide a research basis for the discovery of novel antimicrobials against XD-RAB infection.Methods Ten antipyretic-antidotal TCM were extracted with water,50％ethanol and 95％ethanol respectively,and TCM extracts with different concentrations were prepared,which were co-incubated with the model of XDR-AB-infected Caenorhabditis elegans previously optimized by the research group.The in vivo activity of antipyretic-antidotal TCM against XDR-AB infection was judged through the survival rate of Caenorhabditis elegans.Results With the increase of concentration of turmeric and cortex pseudolaricis extracts,the survival rate of XDR-AB-infec-ted nematodes continued to improve.The water extract,50％ethanol extract,and 95％ethanol extract of turmeric at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 54.2％(compared to the negative control group,P＜0.001),18.8％,and 13.3％,respectively.The water ex-tract,50％ethanol extract,and 95％ethanol extract of cortex pseudolaricis at a concentration of 1 000 μg/mL could increase the survival rates of XDR-AB-infected Caenorhabditis elegans to 47.4％(compared to the negative control group,P＜0.001),23.8％,and 15.8％,respectively.Conclusion The water extracts of turmeric and cortex pseudolaricis have good activity against XDR-AB infection,and their main chemical components can be tested for in vitro antimicrobial efficacy to discover novel antimicrobial agents against XDR-AB infection.

Pancreatic cancer (PC) is a highly fatal disease which originated from pancreatic epithelial and acinar cells, and the survival rate of pancreatic cancer patients is only about 12%. Approximately 95% of pancreatic cancer presents as ductal adenocarcinoma (PDAC). Pancreatic cancer is characterized by high aggressiveness, rapid progression and progression, and high resistance to treatment. Common somatic mutated genes in the early stage of pancreatic cancer include KRAS, CDKN2A, TP53, and SMAD4. Most pancreatic cancer patients are affected by environmental risk factors such as age, sex and diet. Malignant pancreatic cancer is associated with non-invasive, preneoplastic lesions that are thoughted to be precursors, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma (MCN). In recent years, people have gradually improved the therapy and diagnosis of pancreatic cancer, and the contribution of imaging technology, which enhancing the usage of minimally invasive pancreatectomy that typically includes pancreaticoduodenectomy and distal pancreatectomy. However, combined administration of the chemotherapeutic gemcitabine and erlotinib is still considered a potential first-line treatment for advanced pancreatic cancer, but the development of chemoresistance often leads to poor therapeutic outcomes. Based on the current research progress for pancreatic cancer, its treatment currently remains one of the most important challenges in the medical field. Although some new treatment options have been provided, there were minor clinical success achieved and therefore new safe and effective therapies of pancreatic cancer are still an urgent need for patients. Among these new therapies for pancreatic cancer, short peptide-based treatment protocols have attracted great attention. Peptide is a compound formed by linking α-amino acids together in peptide chains. It is also an intermediate product of proteolysis. The short peptide-based therapy has many advantages such as precise targeting, easy preparation and low toxicity. Short peptides usually act as tumor suppressors by targeting and recognizing tumor-specific expressed proteins. Currently, there is an increased interest in peptides in pharmaceutical and development research, and approximate 140 peptide therapeutics are currently being evaluated in clinical trials. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity and simplicity of modification. Peptides have high bioactivity and excellent biodegradability. Clinically, short peptides are increasingly used as combination drugs with chemotherapy for tumor treatment. Peptides can induce cancer cell death by numerous mechanisms and peptides have emerged as a promising drug for the treatment of pancreatic cancer. Here we mainly review the roles of peptides on Wnt/β-catenin, NF-κB, autophagy, and the use of peptides as tracer in pancreatic cancer. We also analyzed the benefits and disadvantages existing in the development process of short peptides, which provide the feasibility of targeted short peptides to become new therapeutic approaches for cancer therapy.

The limitations of traditional image reconstruction algorithms of electrical impedance tomography(EIT)and the advantages of deep learning in nonlinear image reconstruction were introduced.The research progress of three EIT image reconstruction algorithms based on deep learning was summarized,including direct reconstruction method,indirect recon-struction method and implicit reconstruction method.The deficiencies of EIT image reconstruction algorithms based on deep learning were analyzed,and it's pointed out that EIT image reconstruction algorithms based on deep learning should realize further technical breakthroughs in increasing the quality of datasets,enhancing the image interpretability and improving the imaging resolving power.[Chinese Medical Equipment Journal,2024,45(4):98-103]

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the mod-ulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theo-retically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(p-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electro-phoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while pre-senting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Objective To study the efficiency of 3D-STI technology on trastuzumab (TRA) treatment related early myocardial toxicity.Methods In a retrospective study,120 breast cancer postoperative patients receiving TRA treatment and maintenance therapy in this hospital from January 2020 to December 2022 were selected and conducted the routine ultrasound and 3D-STI technological examinations before chemotherapy,in 2,4,6 cycles of chemotherapy.Follow-up continued until October 2023.The patients were divided into the my-ocardial toxicity group and non-myocardial toxicity group according to whether or not developing myocardial toxicity.By combining with the baseline data,the univariate and multivariate logistic regression were em-ployed to analyze and determine the influencing factors of myocardial toxicity.The predictive value of 3D-STI parameters at different time points for myocardial toxicity was evaluated by using the receiver operating char-acteristic (ROC) curve.Results There was no statistically significant difference in 3D-STI technical parame-ters such as GLS,GAS,GCS and GRS before chemotherapy and in 2 cycles of chemotherapy between the myo-cardial toxicity group and the non-myocardial toxicity group (P>0.05);GLS,GAS and GRS after 4,6 cycles of chemotherapy in the myocardial toxicity group were lower than those in the non-myocardial toxicity group (P<0.05).The logistic regression analysis results showed that GLS (OR=0.542,95％CI:0.424-0.694),GAS (OR=0.580,95％CI:0.360-0.936) and GCS (OR=1.699,95％CI:1.035-2.790) after 4 cycles of chemotherapy,and GLS (OR=0.534,95％CI:0.440-0.648),GAS (OR=0.559,95％CI:0.347-0.901) and GCS (OR=1.613,95％CI:1.131-2.300) after 6 cycles of chemotherapy were the influencing factors of myocardial toxicity in TRA treatment after breast cancer surgery (P<0.05).The results of the ROC curve showed that after 4 cycles of chemotherapy,the diagnostic critical value of GLS was-17.23％ and the area under the curve (AUC) was 0.645 (95％CI:0.541-0.749);the diagnostic critical value of GCS was-19.22％ and AUC was 0.556 (95％CI:0.444-0.668).The GLS diagnostic critical value after 6 cycles of chemotherapy was-17.82％,and AUC was 0.856 (95％CI:0.786-0.927);the GAS diagnostic critical value was-27.17％,and AUC was 0.994 (95％CI:0.983-<1.000);the diagnostic critical value of GCS was-18.38％,and AUC was 0.842 (95％CI:0.771-0.913).Conclusion The 3D-STI parameters in 4,6 cycles of chemotherapy could predict the myocardial toxicity after TRA treatment after breast cancer surgery.