OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

ObjectiveTo establish a high-performance liquid chromatography（HPLC） for the quantitative analysis of multiple components in Gegen Qinlian tablets， and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution（TOPSIS）， in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets. MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers， and taking the detection results as variables， SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis（CA）， principal component analysis（PCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） to identify key components affecting the quality. Then， TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method. ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation， the method was found to be stable and reliable， and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin， puerarin， 3′-methoxy puerarin， daidzein， coptisine hydrochloride， epiberberine， jatrorrhizine hydrochloride， berberine hydrochloride， palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35， 24.88-42.32， 4.20-9.36， 4.33-7.60， 2.52-6.44， 0.93-4.10， 0.58-3.05， 10.68-22.92， 0.82-4.82， 11.73-60.16 mg·g^-1， respectively. Among them， puerarin， berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories， PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%， and OPLS-DA screened out 4 differential markers with variable importance in the projection（VIP） values>1.0， namely baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride， which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index（C_i） values of different manufacturers were different. Among them， the C_i of manufacturer B was ranked higher， indicating potentially superior quality， while the C_i of manufacturer A was ranked lower， suggesting potentially inferior quality. ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets， and the content uniformity of the same manufacturer is good， while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis， it is found that the content differences of Gegen Qinlian tablets may be related to baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride.

BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.

BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.

Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.

OBJECTIVE: To construct a longitudinal trajectory model of arterial oxygen tension (PaO₂) within 24 hours after cardiac arrest (CA). METHODS: A retrospective cohort study was conducted. CA patients admitted to the ICU from 2014 to 2015 were selected from the eICU Collaborative Research Database (eICU-CRD). Data about patients' demographic characteristics, history of comorbidities, laboratory test indicators within 24 hours of intensive care unit (ICU) admission [including all PaO₂ data and arterial carbon dioxide tension (PaCO₂)], vasopressor use, and clinical outcomes were extracted from the database. The primary outcome variable was all-cause in-hospital mortality. Group-based trajectory model (GBTM) were built based on the changes in PaO₂ within 24 hours of ICU admission, and patients were grouped according to their initial static PaO₂ values upon ICU admission. Multivariable adjusted Poisson regression analysis was used to compare the in-hospital mortality risk among patients in different PaO₂ dynamic trajectory groups. Sensitivity analyses were performed using multivariable logistic regression and multivariable adjusted Poisson regression without imputation of missing values. RESULTS: A total of 3 866 CA patients were included. Three GBTM trajectory groups were identified based on PaO₂ changes within 24 hours of ICU admission: Group-1 (low level first increased then decreased, 148 cases), Group-2 (sustained low level, 3 040 cases), and Group-3 (first high level then decreased, 678 cases). Significant differences were found among the three groups in age, body weight, maximum serum potassium, maximum PaCO₂, minimum hemoglobin (Hb), vasopressor use, total hospitalization time, ICU stay, and hospital mortality. After incorporating variables with significant differences into the multivariable adjusted Poisson regression model, results showed that compared to Group-2 patients, patients in Group-1 and Group-3 had an increased risk of all-cause in-hospital mortality [Group-1 adjusted relative risk (aRR) = 1.20, 95% confidence interval (95%CI) was 1.02-1.41; Group-3 aRR = 1.11, 95%CI was 1.01-1.24]. Based on initial static PaO₂ values at ICU admission, patients were divided into four groups: PaO₂ < 100 mmHg (1 mmHg = 0.133 kPa; 1 217 cases), PaO₂ 100-200 mmHg (569 cases), PaO₂ 201-300 mmHg (547 cases), and PaO₂ > 300 mmHg (1 082 cases). Multivariable adjusted Poisson regression analysis indicated a significant upward trend in aRR for the latter three groups compared to the PaO₂ < 100 mmHg group. Sensitivity analyses revealed that compared to Group-2, patients in Group-1 and Group-3 had a significantly increased risk of all-cause in-hospital mortality (both P < 0.05). CONCLUSIONS Within 24 hours after return of spontaneous circulation in CA patients, PaO₂ exhibits different dynamic trajectories, and patients with hyperoxia have an increased risk of in-hospital mortality.
Humans ; Retrospective Studies ; Hospital Mortality ; Heart Arrest/blood* ; Prognosis ; Oxygen/blood* ; Intensive Care Units ; Cardiopulmonary Resuscitation ; Male ; Female ; Middle Aged

This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L^-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
Animals ; Mice ; RANK Ligand/genetics* ; RAW 264.7 Cells ; Osteoclasts/metabolism* ; Benzopyrans/isolation & purification* ; Osteogenesis/drug effects* ; Macrophages/metabolism* ; Molecular Structure ; Pigments, Biological/isolation & purification* ; Ascomycota/chemistry* ; NF-kappa B/genetics* ; Cell Differentiation/drug effects*

Objective To investigate a technical approach suitable for the clarification and concentration of Coxackievirus A16(CA16) harvest solution, aiming to effectively remove impurity particles and proteins while achieving high antigen concentration.Methods The virus harvest solution underwent two-stage filtration pretreatment. Antigen recovery rate,membrane flux, and turbidity were utilized as evaluation metrics at each stage to examine the effects of various membrane materials, pore sizes, and structures on clarifying efficacy. Subsequently, clarified harvest liquid was concentrated using a100 KD polyether sulfone membrane, and the changes in antigen content and protein content were analyzed to determine the optimal concentration multiples, washing cycles, and sampling intervals. The sample size was scaled up for pilot testing where the harvested liquid was clarified, filtered and subjected to ultrafiltration based on the optimized parameters. The linear scalability of this process was assessed using antigen recovery rates and protein removal rates as indicators.Results In the first stage, 0. 45 ??m glass fiber membranes were employed while in the second stage 0. 45 ??m polyether sulfone membranes were used. The optimal conditions for ultrafiltration concentration included a concentration factor ranging from 30 to50 times with four washing filtrations followed by four sampling collections. At pilot scale testing, post-clarification resulted in a turbidity reduction of CA16 virus by 96. 00%, with an antigen recovery rate of 89. 49%. Following ultrafiltration concentration yielded an antigen recovery rate of 87. 23% alongside a protein removal rate reaching 91. 17%.Conclusion The optimized ultrafiltration concentration technology not only reduces protein content but also achieves high levels of antigen recovery while demonstrating excellent potential for linear amplification.

Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

Objective: To analyze the epidemiological characteristics and trends of other infectious diarrhea among children under 18 years old in Guangzhou City from 2014 to 2020, and to explore the correlation between climatic factors and the incidence of the disease, so as to provide reference for the early prevention of infectious diseases. Methods: The data of cases of other infectious diarrhea and meteorological data of children under 18 years old in Guangzhou City from 2014 to 2020 were collected through the Chinese Infectious Disease Reporting System and the Guangzhou Meteorological Bureau. The correlation between meteorological factors and the incidence of other infectious diarrhea was analyzed using negative binomial regression. Results: A total of 104 566 cases of other infectious diarrhea among children under 18 years old were reported in Guangzhou City from 2014 to 2020, with a male to female ratio of 1.48∶1. The incidence rate was the highest in 2017 (980.83 per 100 000) and the lowest in 2020 (388.22 per 100 000). The peak of incidence occurred from October to March of the following year. Children under 5 years old accounted for 87.95% of all cases. The number of cases of other infectious diarrhea was negatively correlated with the temperature of the previous 6 days ( IRR = -0.07 ), and positively correlated with the temperature difference on the day of onset ( IRR =0.02) (both P <0.05). It was also positively correlated with the wind speed of the previous 7 days ( IRR=0.07, P <0.05), but there was no statistically significant correlation with the relative humidity on the day of onset ( IRR=-0.00, P >0.05). Conclusions Low temperature, large temperature difference, and high wind speed can increase the risk of other infectious diarrhea. It is necessary to strengthen the prediction and early warning in conjunction with meteorological changes, and warn kindergartens and schools to enhance preventive measures against the clustering of other infectious diarrhea cases.