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.

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.

Objective:To investigate the impacts of 1,25-dihydroxyvitamin D 3 (VD) and Lactobacillus plantarum (LP) on intestinal flora in animals with metabolic dysfunction-associated fatty liver disease (MAFLD) and their possible mechanisms. Methods:A methionine- choline-deficient (MCD) diet-induced rat model of MAFLD was created. Forty 10-week-old male Sprague-Dawley rats were randomized into methionine-choline-sufficient (MCS) group, MCD group, VD group, LP group, and VD-LP group, with 8 rats in each group. The intervention groups (VD group, LP group, and VD-LP group) were gastrically fed with VD peanut oil solution (6 ng/100 g daily), Lactobacillus plantarum solution (2×10 9CFU/100 g daily), and a combination of these two solutions, respectively. MCS group, MCD group, and LP group were given the same volume of peanut oil on a daily basis. Fecal samples from rats were collected at week 4 and analyzed using 16S rRNA gene sequencing for fecal flora structure. Portal vein blood samples were collected to detect liver biochemistry and lipopolysaccharide (LPS) levels. Pathological changes in liver and terminal ileum tissues were observed using hematoxylin and eosin (H&E) staining. Results:Compared with the MCS group, the MCD group exhibited massive steatosis and lipid infiltration in liver tissues, markedly thinned ileum mucosa, severely damaged villi structure, excessive necrotic and shedding of epithelial cells, and infiltration of inflammatory cells. Compared with the histopathological changes in the MCD group, the steatosis and lipid infiltration of liver tissue, the damage to the ileal mucosa structure and epithelial cells, and the infiltration of inflammatory cells were alleviated in the VD group, LP group, and VD-LP group. Compared with MCS group, the MCD group had significantly higher serum alanine aminotransferase (ALT) (158.50±14.03 U/L vs. 20.38±7.39 U/L), aspartate aminotransferase (AST) (43.88±11.36 U/L vs. 25.75±5.90 U/L), total bile acid (TBA) (140.60±11.77 μmol/L vs. 19.96±4.31 μmol/L), and LPS (16.57±1.19 pg/ml vs. 7.43±0.95 pg/ml) (All P<0.001),which confirmed the successful establishment of rat models of MAFLD. Serum ALT, AST, TBA, and LPS levels in all the three intervention groups were significantly lower than those in MCD group, and the most significant reductions in ALT (51.38±9.05 U/L vs. 158.50±14.03 U/L), AST (55.88±12.19 U/L vs. 143.88±11.36 U/L), TBA (21.00±8.17 μmol/L vs. 140.60±11.77 μmol/L), and LPS (9.72±0.71 pg/ml vs. 16.57±1.19 pg/ml) were seen in the VD-LP group. The microbiota in the MCD group predominantly featured Muribaculaceae, while the MCS group and other intervention groups primarily harbored Lactobacillus. Firmicutes and Lactobacillus were significantly decreased in the MCD group ,while Bacteroidete, Proteobacteria, Verrucomicrobiota, Prevotellaceae UCG-003, Escherichia coli, Bacteroides, and Enterococcus increased significantly. The opposite was true for each intervention group. There were significant differences in Lactobacillus between MCD group and the other four groups. Conclusion:VD and LP can remarkably improve lipid deposition in MAFLD by regulating intestinal flora.

In July 2024,the Diagnosis Related Groups(DRG)2.0 is released based on the Notice from the National Healthcare Security Administration on Issuing the DRG 2.0 and Deepening the Relevant Work.Compared with DRG 1.1,version 2.0 was established based on a wider range of suggestions regarding the Adjacent Diagnosis Related Groups(ADRG),Major Comorbidity or Complication(MCC),and Comorbidity or Complication(CC)from various institutions.A list of disease diagnoses and surgical operations that are not used as grouping rules was compiled,and grouping efficacy was further improved by upgrading the algorithms for MCC and CC with the help of AI.Meanwhile,it is necessary to pay more attention to the number of cases of ADRG,the better methods to list the MCC/CC,the suggestions of various doctors and continuously standardize the data and update the grouping scheme of DRG.

OBJECTIVE To compare the clinical and microbiological characteristics of patients with bloodstream in-fection(BSI)and to summarize the risk factors for death in these patients.METHODS Clinical data of 528 patients with BSI admitted to Xijing Hospital,the Fourth Military Medical University from Jul.2018 to Feb.2023 were collected.The clinical characteristics,pathogens,antibacterial drug therapy and 28-day case-fatality rate of the pa-tients with BSI were analyzed.RESULTS Among the 528 patients with BSI,there were 139 patients with commu-nity-associated infection,69 patients with health care-associated infection,and 320 patients with hospital-associat-ed infection.The predominant pathogens isolated from patients with community-associated infection and health care-associated infection were Escherichia coli(53.96％and 42.03％,respectively),while Klebsiella pneumoni-ae was the main pathogen in patients with hospital-associated infection(24.38％),with a wide variety of major pathogens identified.The drug resistance profiles of E.coli and K.pneumoniae isolated from patients with health care-associated infection were similar to those isolated from patients with hospital-associated infection but were significantly low compared to those isolated from patients with community-associated infection.Compared to pa-tients with community-associated infection,those with health care-associated infection and hospital-associated in-fection had high 28-day case-fatality rates.Thrombocytopenia(HR=1.764,95％CI:1.275-2.440,P=0.001),hypoalbuminemia(HR=2.320,95％CI:1.595-3.374,P＜0.001),coagulation dysfunction(HR=1.605,95％CI:1.141-2.258,P=0.007),procalcitonin＞2.0 ng/ml(HR=3.747,95％CI:1.339-10.485,P=0.012),Charlson comorbidity index ≥5(HR=1.578,95％CI:1.110-2.244,P=0.011)and central ve-nous catheterization(HR=1.848,95％CI:1.322-2.583,P＜0.001)were risk factors for 28-day mortality,while appropriate targeted antibacterial drug therapy(HR=0.399,95％CI:0.291-0.546,P＜0.001)was a protective factor.CONCLUSION Antibacterial drug therapy for patients with health care-associated infection should be guided by their unique pathogens and resistance profiles,and individualized regimens should be devel-oped based on the site and source of infection,regional microbiological characteristics and disease severity to re-duce unnecessary use of antibacterial drug.

Objective:To investigate the impacts of 1,25-dihydroxyvitamin D 3 (VD) and Lactobacillus plantarum (LP) on intestinal flora in animals with metabolic dysfunction-associated fatty liver disease (MAFLD) and their possible mechanisms. Methods:A methionine- choline-deficient (MCD) diet-induced rat model of MAFLD was created. Forty 10-week-old male Sprague-Dawley rats were randomized into methionine-choline-sufficient (MCS) group, MCD group, VD group, LP group, and VD-LP group, with 8 rats in each group. The intervention groups (VD group, LP group, and VD-LP group) were gastrically fed with VD peanut oil solution (6 ng/100 g daily), Lactobacillus plantarum solution (2×10 9CFU/100 g daily), and a combination of these two solutions, respectively. MCS group, MCD group, and LP group were given the same volume of peanut oil on a daily basis. Fecal samples from rats were collected at week 4 and analyzed using 16S rRNA gene sequencing for fecal flora structure. Portal vein blood samples were collected to detect liver biochemistry and lipopolysaccharide (LPS) levels. Pathological changes in liver and terminal ileum tissues were observed using hematoxylin and eosin (H&E) staining. Results:Compared with the MCS group, the MCD group exhibited massive steatosis and lipid infiltration in liver tissues, markedly thinned ileum mucosa, severely damaged villi structure, excessive necrotic and shedding of epithelial cells, and infiltration of inflammatory cells. Compared with the histopathological changes in the MCD group, the steatosis and lipid infiltration of liver tissue, the damage to the ileal mucosa structure and epithelial cells, and the infiltration of inflammatory cells were alleviated in the VD group, LP group, and VD-LP group. Compared with MCS group, the MCD group had significantly higher serum alanine aminotransferase (ALT) (158.50±14.03 U/L vs. 20.38±7.39 U/L), aspartate aminotransferase (AST) (43.88±11.36 U/L vs. 25.75±5.90 U/L), total bile acid (TBA) (140.60±11.77 μmol/L vs. 19.96±4.31 μmol/L), and LPS (16.57±1.19 pg/ml vs. 7.43±0.95 pg/ml) (All P<0.001),which confirmed the successful establishment of rat models of MAFLD. Serum ALT, AST, TBA, and LPS levels in all the three intervention groups were significantly lower than those in MCD group, and the most significant reductions in ALT (51.38±9.05 U/L vs. 158.50±14.03 U/L), AST (55.88±12.19 U/L vs. 143.88±11.36 U/L), TBA (21.00±8.17 μmol/L vs. 140.60±11.77 μmol/L), and LPS (9.72±0.71 pg/ml vs. 16.57±1.19 pg/ml) were seen in the VD-LP group. The microbiota in the MCD group predominantly featured Muribaculaceae, while the MCS group and other intervention groups primarily harbored Lactobacillus. Firmicutes and Lactobacillus were significantly decreased in the MCD group ,while Bacteroidete, Proteobacteria, Verrucomicrobiota, Prevotellaceae UCG-003, Escherichia coli, Bacteroides, and Enterococcus increased significantly. The opposite was true for each intervention group. There were significant differences in Lactobacillus between MCD group and the other four groups. Conclusion:VD and LP can remarkably improve lipid deposition in MAFLD by regulating intestinal flora.

Objective:To investigate the effects of baicalin on ferroptosis of mouse fibroblasts (Fbs) under high glucose treatment and its mechanism, and to provide a basis for the treatment of diabetic wounds.Methods:The study was an experimental study. Mouse Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at final molarity of 30.0 mmol/L, and low baicalin group and high baicalin group pretreated with baicalin at final molarties of 5 and 10 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counting kit-8, the reactive oxygen species level in cells was detected by the fluorescent probe method, the levels of malondialdehyde, glutathione, and ferrous ion in cells were detected by colorimetry, and the protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in cells and nuclear factor-erythroid 2-related factor 2 (Nrf2) in cytoplasm and nucleus were detected by Western blotting. Another batch of mouse Fbs were collected and divided into control group, high glucose group, high baicalin group, and high baicalin+ML385 group. The cells in the first three groups were treated as before, the cells in the last group were pretreated with baicalin and ML385 of Nrf2 inhibitor at final molarties of 10 μmol/L and then treated as that in high glucose group. After 48 h of culture, the protein expression levels of SLC7A11 and GPX4 in cells and the protein expression level of Nrf2 in cytoplasm and nucleus were detected as before. Except that the sample number in detecting SLC7A11 and GPX4 was 4, the sample number in detecting other indexes was 3.Results:After 48 h of culture, the cell survival rates in control group, high glucose group, low baicalin group, and high baicalin group were (100.0±10.7)%, (70.0±5.0)%, (80.9±3.2)%, and (91.4±1.9)%, respectively. Compared with those in control group, the cell survival rate, the glutathione level, and SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level were significantly decreased in high glucose group ( P<0.05), and the levels of reactive oxygen species, malondialdehyde, and ferrous ion in cells, and cytoplasmic Nrf2 protein expression level were significantly increased in high glucose group ( P<0.05). Compared with those in high glucose group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in low baicalin group and high baicalin group were significantly increased ( P<0.05), the reactive oxygen species and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in low baicalin group and high baicalin group were significantly decreased ( P<0.05), and the malondialdehyde level in cells in high baicalin group was significantly decreased ( P<0.05). Compared with those in low baicalin group, the cell survival rate, glutathione level, SLC7A11 and GPX4 protein expression levels in cells, and nuclear Nrf2 protein expression level in high baicalin group were significantly increased ( P<0.05), and the reactive oxygen species, malondialdehyde, and ferrous ion levels in cells, and cytoplasmic Nrf2 protein expression level in high baicalin group were significantly decreased ( P<0.05). After 48 h of culture, compared with those in control group, the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased ( P<0.05), and the cytoplasmic Nrf2 protein expression level was significantly increased in high glucose group ( P<0.05); compared with those in high glucose group, the cytoplasmic Nrf2 protein expression level was significantly decreased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly increased in high baicalin group ( P<0.05); compared with those in high baicalin group, the cytoplasmic Nrf2 protein expression level was significantly increased ( P<0.05), and the nuclear Nrf2 protein expression level and SLC7A11 and GPX4 protein expression levels in cells were significantly decreased in high baicalin+ML385 group ( P<0.05). Conclusions:Baicalin can inhibit the occurrence of ferroptosis in cells by activating the Nrf2 signaling pathway and up-regulating the expressions of proteins related to SLC7A11/GPX4 axis in Fbs in high glucose treatment, thus increasing the cell survival rate.

Serotonin syndrome (SS), also known as serotonin toxicity, is a rare but life-threatening drug reaction syndrome. This case involves a 17-year-old female patient who developed tremors, fatigue, and tachycardia after taking fluoxetine combined with bupropion and tandospirone for five days. SS was highly suspected, and her symptoms improved following treatment targeted at serotonin syndrome. This case is reported to raise awareness among clinicians about the potential adverse reactions of drug combinations, the importance of early identification of SS symptoms, and precautions when prescribing combined medications to avoid serious consequences.