OBJECTIVE To compare the long-term cost-effectiveness of gonadotrophin-releasing hormone analogue （GnRHa） combined with recombinant human growth hormone （rhGH） （combination therapy regimen） versus GnRHa monotherapy （monotherapy regimen） in the treatment of central precocious puberty （CPP）. METHODS From the societal perspective and based on a real-world study conducted at West China Second Hospital of Sichuan University， the cost-effectiveness analysis was performed to compare the long-term cost-effectiveness of two pharmacotherapy regimens for CPP girls， with final height as outcome indexes， using per capita disposable income of rural residents and urban residents （20 133-49 283 yuan） in 2022 as the social willing-to-pay （WTP） threshold. The robustness of the basic analysis result was verified by using one-way sensitivity analysis and probability sensitivity analysis， and the cost-effectiveness of different combinations of long-acting preparations was compared using scenario analysis. RESULTS The basic analysis result showed that the combination therapy regimen required an additional cost of 25 193.49 yuan for every one-centimeter improvement in the final height of girls with CPP compared with the monotherapy regimen， which was not cost-effective for residents in rural areas， but it was cost-effective for residents in urban areas. One-way sensitivity analysis showed that the uncertain factors with potential impacts on the results were， in order， the price of rhGH， the final height of pediatric patients in the combination therapy regimen group， the course of rhGH in the combination therapy regimen group， and the final height of pediatric patients in the monotherapy regimen group. Probabilistic sensitivity analysis indicated that the probability of the combination therapy regimen being cost-effective was higher than that of the monotherapy regimen when WTP was more than 26 010 yuan/cm. When GnRHa long-acting preparation was used for intramuscular injection every 3 months， the combination therapy regimen was not cost-effective for rural residents， but was cost-effective for urban residents； when rhGH long-acting preparation was injected subcutaneously once a week， the combination therapy regimen was not cost-effective for residents in both rural areas and urban areas. CONCLUSIONS The combination of GnRHa and rhGH is only recommended for CPP children with better affordability to improve final height. The benefits， risks， and affordability of treatment should be comprehensively considered before the decisions on pharmacotherapy， to avoid abuse of rhGH due to the blind pursuit of height growth.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)％,(61.91±4.40)％and(118.07±10.01)％;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.

Objective To explore the role of Panax notoginseng saponins(PNS)in regulating the expression of sortilin and ATP-binding cassette transporter A1(ABCA1)in macrophages,and the effect of PNS on inhibiting formation of foam cells and the potential mechanism of PNS adjusting sortilin expression and cholesterol metabolism.Methods The macrophages were divided into five groups as follows:group A(only added with cell culture),group B(transfected with negative control lentivirus),group C(transfected with lentivirus-mediated sortilin overexpression),group D(transfected with lentivirus-mediated sortilin overexpression+60 μg·mL-1PNS),group E(transfected with lentivirus-mediated sortilin overexpression+10 μmol·L-1 mitogen-activated protein kinase kinase(MEK)inhibitor PD98059+60 μg·mL-1 PNS).The protein contents of sortilin,ABCA1,extracellular signal-regulated kinase(ERK)and phosphorylated-ERK(p-ERK)were evaluated with Western blot.All the cells in five groups were cultured with 50 μg·mL-1ox-LDL to form foam cells.The lipid in macrophages was investigated with red O assay.Results The relative expression levels of sortilin protein were 1.00±0.08,0.91±0.15,2.28±0.13,1.62±0.09 and 2.01±0.08;the relative expression levels of ABCA1 protein were 1.00±0.01,0.92±0.07,0.29±0.04,0.66±0.09 and 0.44±0.07;the ratios of p-ERK/ERK protein were 1.00±0.09,0.92±0.05,1.03±0.12,2.00±0.12 and 1.64±0.14;the contents of lipid in macrophages were(4.82±2.19)％,(6.70±0.88)％,(44.56±4.15)％,(27.66±3.25)％and(41.67±5.45)％.Except the ratios of p-ERK/ERK,the other parameters between group C and group A were statistically significant difference(all P＜0.01).Meanwhile,there were also statistically significant difference between group D and group C as well as group D and group E(P＜0.05,P＜0.01).Conclusion PNS inhibits the lipid accumulation in macrophages through upregulating ABCA1 and downregulating sortilin,and ERK signaling pathway may be as one of important mechanisms influencing the expression of sortilin and ABCA1 mediated by PNS.

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury （MIRI） in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group， normal administration group， MIRI control group and MIRI administration group， with 5 rats in each group. After drug intervention or modeling and drug intervention， chromatographic separation plasma samples were collected， and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps， the maps of each plasma sample， and the relevant literature. At the same time， the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis， the differential transitional components were screened out according to the value of variable importance in the projection （VIP）＞1， to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group， MIRI group， positive control group （Compound danshen tablets 0.2 g/kg， 3 times a day）， and potentially active compound groups （10 mg/kg， twice a day）， with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically， for 3 consecutive days. The activity of superoxide dismutase （SOD）， the leakages of lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower， and 14 of them were determined， including gallic acid， catechin， protocatechuic acid and so on. There were fifteen （including 6 absorbed prototype components and 9 metabolites） and nineteen transitional components （including 6 absorbed prototype components and 13 metabolites） in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats， and the VIP values of kaempferol glucuronidation metabolites， quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group， the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group （P＜0.01）， and the leakages of LDH， CK-MB， and cTnⅠ in the plasma of MIRI rats were reduced significantly （P＜0.01）. CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine， quercetin， kaempferol and kaempferol-3-O-β-D-glucoside.

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.