ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

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

Objective To explore the protective mechanism of baicalin regulating NOD like receptor thermal protein domain associated protein 3(NLRP3)inflammasomes against acne.Methods Compound acne models were prepared by intradermal injection of Propionibacterium acnes into the auricle.Rats were randomly divided into control group(normal rats were given physiological saline by gavage),model group(acne model rats were given physiological saline by gavage),experimental-L,-M,-H groups(acne model rats were given 25,50,and 100 mg·kg-1 of baicalin by gavage),and positive control group(acne model rats were given 3.125 mg·kg-1 of isotretinoin by gavage),with 10 rats in each group.Observe the morphology of rat auricles;enzyme linked immunosorbent assay(ELISA)was used to detect the level of inflammation in serum;hematoxylin-eosin staining was used to detect pathological changes in rat auricle tissue;Western blotting was used to detect the protein expression level in the auricle tissue.Results After drug treatment,the auricular thickness of rats in the control,model,experimental-H and positive control groups were(0.42±0.05),(0.75±0.10),(0.49±0.05)and(0.50±0.05)mm;the serum levels of tumor necrosis factor-α were(20.46±2.13),(62.32±5.47),(23.27±2.26)and(25.41±2.28)pg·mL-1;interleukin-1 β levels were(11.38±1.26),(31.62±2.58),(15.61±1.35)and(16.72±1.38)pg·mL-1;interleukin-6 levels were(10.62±1.02),(25.43±2.51),(13.27±1.15)and(14.01±1.17)pg·mL-1;NLRP3 protein expression levels in auricular tissues were 0.23±0.03,0.81±0.08,0.30±0.04 and 0.32±0.04;and Caspase-1 protein expression levels were 0.31±0.04,0.76±0.08,0.39±0.04 and 0.41±0.04;matrix metalloproteinase-2 protein expression levels were 0.35±0.04,0.86±0.10,0.40±0.05 and 0.42±0.05.Compared with the model group,the above indexes in the experimental-H group were statistically significant(all P＜0.05).Conclusion Baicalin can inhibit the inflammatory response in acne rats,and its mechanism of action may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

Background The threshold limit values (TLVs) established and regularly updated by the American Conference of Governmental Industrial Hygienists (ACGIH) are widely adopted and referenced globally, serving as a crucial reference for China's occupational exposure limits (OELs). It is necessary to track it regularly and compare it with China's OELs. Objective To compare the OELs stipulated in Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) and the ACGIH TLVs (2024) and to provide references for subsequent formulation and revision of OELs in China. Methods The OELs specified in GBZ 2.1—2019 and the TLVs issued by ACGIH were used to establish a database using Microsoft Excel 2019 software. Cross verification was conducted through matching Chemical Abstracts Service Registry Numbers (CAS Rn) and both Chinese and English names to ensure accuracy. Then, comparisons and analyses were carried out based on the type of limit values, which were matched as follows: permissible concentration-time weighted average (PC-TWA) with threshold limit value-time weighted average (TLV-TWA), permissible concentration-short term exposure limit (PC-STEL) with threshold limit value-short term exposure limit (TLV-STEL), and maximum allowable concentration (MAC) with threshold limit value-ceiling (TLV-C). Comparisons included types, quantities, and sizes of limits. Results The GBZ 2.1—2019 OELs and the ACGIH TLVs (2024) were generally consistent in terms of types and definitions, but there were differences in the number and size of the limits. In terms of the number of limits, GBZ 2.1—2019 specified 365 OELs for 358 chemical hazardous agents, while ACGIH TLVs (2024) included 316 corresponding limits. Among these, 148 (46.9%) limits were consistent, 38 (12.0%) were basically consistent, and 130 (41.1%) were inconsistent. In terms of the size of the limits, out of the 130 inconsistent limits, 51 OELs were lower than the corresponding TLVs, 67 OELs were higher than the corresponding TLVs, and 12 were under different limit types. For some chemical hazardous agents, their OELs were significantly lower or higher than their TLVs. Conclusion Some of the OELs for chemical hazardous agents specified in GBZ 2.1—2019 are significantly lower or higher than the TLVs. For these chemical hazardous factors, it is recommended to prioritize their inclusion in research projects and to complete the revisions as soon as possible based on the latest scientific evidence.

Objective To evaluate the efficacy,safety,and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia(IDA)by rapid health technology assessment,and to provide evidence for clinical decision-making.Methods PubMed,Embase,the Cochrane Library,CNKI,WanFang,SinoMed,and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports,systematic reviews/Meta-analysis,and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose(IS),iron dextran(ID),ferric carboxymaltose(FCM),and iron isomaltoside(IIM)from the inception to August 15,2024.Two researchers independently screened the studies,extracted data and assessed the quality of included studies.The results were then qualitatively described and analyzed.Results A total of 32 studies were included,including one health technology assessment report,16 systematic reviews/Meta-analysis,and 15 pharmacoeconomic evaluations.In terms of effectiveness,FCM had a higher response rate than that of IS(P＜0.05),FCM and IIM had no statistical difference(P＞0.05).Regarding hemoglobin level change,patients treated with FCM had higher hemoglobin levels than those treated with IS(P＜0.05);the improvement in hemoglobin levels between IIM and FCM was inconclusive.In terms of ferritin level change,FCM might be superior to the other three intravenous iron formulations.In terms of safety,the adverse event rates for FCM,IS,ID and IIM were 12.0％,15.3％,12.0％and 17.0％,respectively;IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS(P＜0.05);FCM had the highest rate of hypophosphatemia among the four formulations(P＜0.05),and there was no significant difference among IIM,IS and ID(P＞0.05);IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS.In terms of economy,FCM and IIM had an economic advantage compared to IS.The economic efficiency ranking among IS,ID,and FCM was in the order of FCM,ID,and IS,the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.Conclusion FCM and IIM have good efficacy,safety and economy in the treatment of IDA,but most of the included economy studies based on foreign populations,and domestic economic studies need to be further demonstrated.

Objective The equilibrium solubility and oil-water partition coefficient of caffeic acid in different pH environments were determined,and its biopharmaceutical classification system(BCS)classification was speculated.The dissolution curve of caffeic acid tablets was determined,and the above parameters were substituted into the rat PBPK model for modeling.Gastroplus software was used to predict the in vitro and in vivo correlation of caffeic acid tablets.Methods Quantitative analysis of caffeic acid was performed by a high-performance liquid chromatography in this research,the chromatographic column was Agilent Eclipse Plus C18(4.6 mm×250 mm,5 &mu;m),the mobile phase was 0.32%glacial acetic acid solution-methanol(70∶30),the flow rate was 1.0 mL·min-1,the detection wavelength was 323 nm,the column temperature was 25℃,the injection volume was 10 &mu;L.The equilibrium solubility,solubility volume(DSV)and oil-water partition coefficient(P)of caffeic acid in different pH buffers were measured by the shake flask method and n-octanol-water system,and its BCS classification was speculated.The dissolution curves of caffeic acid tablets in water,pH1.2,pH4.5 and pH6.8 were determined.The Z-Factor values of these dissolution curves were analyzed using Gastroplus software.The relevant parameters were substituted into the physiological pharmacokinetic(PBPK)model of rats to simulate the in vivo pharmacokinetic(PK)curve of rats.Compared with the measured PK curve that was reported previously,the correlation between in vivo and in vitro was speculated.Results The equilibrium solubility of caffeic acid in pH1.2,pH4.5 and pH6.8 were 0.676,1.266 and 4.624 mg·L-1,and the DSV were 443 787,236 967 and 64 879 mL,which showed that caffeic acid was an insoluble drug which had a strong pH dependence in dissolution;The oil-water partition coefficients(P)of caffeic acid in water,pH1.2 buffer,pH4.5 buffer and pH6.8 buffer were 4.33(logP=0.64),28.87(logP=1.46),19.77(logP=1.30)and 0.28(logP=-0.56),which indicated that caffeic acid was a BCS Ⅱ drug with high permeability.The results of the Cmax,tmax and AUC of caffeic acid in rats obtained by a software simulation was 0.358 &mu;g·mL-1,0.39 h and 0.320 &mu;g·h-1·mL-1,which was basically matched with the results[Cmax∶(0.250±0.037)&mu;g·mL-1、tmax∶(0.33±0.12)h、AUC∶(0.303±0.024)&mu;g·h-1·mL-1]that reported previously,so was the PK curves.Conclusion Caffeic acid is a drug with low solubility and high permeability.It is speculated that caffeic acid is a BCS Ⅱ drug,and its tablets show a high correlation in vivo and in vitro in rats.

Objective To investigate the safety and effectiveness of colon polypectomy in patients taking antithrombotic drugs.Methods Polyps treated with endoscopic polypectomy at the Department of Gastroenterology,Fu Wai Hospital,Chinese Academy of Medical Sciences,from August 2022 to August 2023 were retrospectively analyzed for the site of polyp,postoperative delayed hemorrhage,perforation,and the completeness of resection,specimen retrieval,and the occurrence of postoperative ischemic events.Results A total of 103 polyps were included in the study,which were divided into two groups according to whether the diameter of the polyp was＞10 mm(87 cases in the small polyp group vs 16 cases in the large polyp group),and there was no statistically significant difference between the two groups in terms of the site of the polyp,its morphology,the type of antithrombotic drug taken,the rate of curative resection,the rate of postoperative hemorrhagic events,and the incidence of postoperative ischemic events;the large polyp group chose more often to undergo EMR treatment(small polyp group vs.large polyp group,4.6％vs.45.5％,P=0.004);postoperative pathology was more adenomatous polyps in the large polyp group(small polyp group vs.large polyp group,77.0％vs.93.8％,P=0.027).Conclusion Endoscopic polypectomy can be used safely and effectively in patients taking antithrombotic drugs.

Objective To investigate the causes of a cluster of suspected neonatal carbapenem-resistant Klebsiella pneumoniae(CRKP)bloodstream infection(BSI)in the neonatal department of a hospital,and provide references for the effective control of the occurrence of healthcare-associated infection(HAI).Methods Epidemiological in-vestigation on 3 neonates with CRKP BSI in the neonatal department from January 31 to February 6,2023 was per-formed.Specimens from environmental object surfaces were taken for environmental hygiene monitoring,and effec-tive control measures were taken according to the risk factors.Results From January 31 to February 6,2023,a to-tal of 60 neonates were admitted in the neonatal department,including 16 with peripherally inserted central venous catheter(PICC).Three neonates had CRKP BSI,with a incidence of 5.00％.There were 33 hospitalized neonates on the day(February 7)when the cluster of HAI was reported,with a prevalence rate of 9.09％(3/33).CRKP BSI rate in the neonatal department of this hospital from January 31 to February 6,2023 was higher than that in 2022(P＜0.001).The incubators of the 3 neonates with CRKP BSI were in the same ward and adjacent to each other.The first neonate with CRKP BSI(who developed BSI on January 31)underwent PICC maintenance on Feb-ruary 4,and the other 2 neonates with PICC maintenance immediately following the first one also developed CRKP BSI.CRKP were isolated from blood culture of all 3 neonates,and antimicrobial susceptibility testing results were consistent.Conclusion The occurrence of the cluster event of neonatal CRKP BSI may be related to the failure of strict implementation of aseptic procedures during PICC maintenance and cross contamination among items.