OBJECTIVE To evaluate the cost-effectiveness of ripretinib versus sunitinib as a second-line treatment option for patients with advanced gastrointestinal stromal tumors （GIST）. METHODS Based on the data of INTRIGUE study， a dynamic Markov model was constructed， with a cycle of 6 weeks； this model was used to simulate patients’ direct medical costs and quality- adjusted life years （QALYs） over 15 years. Using the incremental cost-effectiveness ratio （ICER） as the evaluation metric， a comparison was made between the ICER and the willingness-to-pay （WTP） threshold （3 times the per capita gross domestic product， which amounts to 268 200 yuan/QALY）. One-way sensitivity analyses and probabilistic sensitivity analyses were performed on the model outputs to examine the stability of the model. RESULTS The health benefits of ripretinib were lower than those of sunitinib （1.21 QALYs vs. 1.31 QALYs）. Still， the costs were higher （323 401.88 yuan vs. 227 532.40 yuan）， making it an inferior regimen. The results of the one-way sensitivity analysis suggested that the cost of ripretinib and sunitinib， and the health utility value in progression-free survival status had a greater impact on the ICER of the model. Probabilistic sensitivity analysis suggested that the results of the study were stable， and the probability of the cost-effectiveness advantage of ripretinib was always much lower than that of sunitinib with the increase of WTP threshold， and showed a decreasing trend. CONCLUSIONS In the current economic context of China， ripretinib does not have a cost-effectiveness advantage over sunitinib as a second-line treatment for advanced GIST.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

OBJECTIVE To identify and analyze adverse drug event （ADE） signals associated with tirzepatide based on the FDA Adverse Event Reporting System （FAERS） database， providing a reference for clinical medication safety. METHODS ADE reports from January 1， 2022， to June 30， 2024， with tirzepatide as the primary suspected drug， were extracted from the FAERS database. Medical Dictionary for Regulatory Activities was used to systematically categorize the selected system organ class （SOC） and preferred term of ADE. Signal mining and analysis were performed using the reporting odds ratio method and the proportional reporting ratio method. RESULTS A total of 39 229 ADE reports related to tirzepatide were obtained， including 3 934 severe ADE reports （10.03%）. The majority of severe ADE reports were related to hospitalization or prolonged hospitalization （3.82%）， involving 131 positive ADE signals. Among the reports with documented patient gender and age， 26 195 were female （66.77%）， 7 869 were male （20.06%）， and the majority of patients were aged 18-64 years （54.26%）. The top three most frequently reported ADE were injection site pain， nausea， and injection site hemorrhage. Strong ADE signals not mentioned in the tirzepatide instruction included injection site coldness， starvation ketoacidosis， injection site hemorrhage， hunger， elevated adrenaline， injection site skin cracking， binge eating， skin laxity， intestinal sepsis， lack of satiety， and dysesthesia. Subgroup analysis for patient’s gender and age showed differences in the proportion of ADE reports across different SOC. Male patients or those aged≥65 years had a higher risk of gastrointestinal system disorders compared to female patients or those aged ＜65 years. CONCLUSIONS In clinical use of tirzepatide， in addition to monitoring ADE listed in the instruction， attention should also be paid to ADE not mentioned in the instruction， such as injection site coldness， starvation ketoacidosis， injection site hemorrhage， elevated adrenaline， and intestinal sepsis， to ensure patient safety.

OBJECTIVE To comparatively analyze tumor staging versus clinical staging in reimbursement scope restrictions under medical insurance for antineoplastic agents in order to better implement the medicare drug payment policy. METHODS Antineoplastic agents included in the National Basic Medical Insurance， Workers’ Compensation Insurance and Maternity Insurance Drug Catalogue （2024） （hereinafter referred to as the “Medical Insurance Catalog”） were used as research subject to compile and analyze reimbursement scope restrictions regarding tumor staging. By consulting clinical diagnosis and treatment guidelines and relevant literature， the tumor staging in reimbursement scope restrictions of the Medical Insurance Catalog was mapped and compared with clinical staging. RESULTS & CONCLUSIONS A total of 89 antineoplastic agents’ medical insurance payments had tumor staging. Among these， there were 86 western drugs （including 17 ordinary western drugs， 68 negotiated drugs， and 1 competitive drug） and 3 Chinese patent medicines （including 1 ordinary Chinese patent medicine and 2 negotiated drugs）. Non-small cell lung cancer involved the most restricted payment drugs， with 36 drugs. The tumor staging in reimbursement scope restrictions was mostly “metastatic” and “locally advanced”， involving 67 and 48 drugs respectively. Tumor staging in most reimbursement scope restrictions could correspond to the clinical staging of the tumor. However， mid-advanced esophageal cancer， unresectable gastrointestinal stromal tumors， unresectable locally advanced neuroendocrine tumors， locally advanced basal cell carcinoma， and unresectable neurofibromatosis type Ⅰ did not have a corresponding clinical staging mentioned in authoritative guidelines or high-quality clinical studies and need to be determined by the clinic according to the actual situation of the patient. Therefore， it is recommended that the interpretation of tumor staging in reimbursement scope restrictions should be accurately defined and standardized， so as to improve the accuracy of the drug payment policy in the actual implementation process.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

The pathogenesis of varicocele infertility is complex, and currently, there is no specific drug for clinical treatment, traditional Chinese medicine (TCM) has certain advantages in improving clinical symptoms of patients and improving sperm quality. Based on the theory of deficiency and stasis in TCM and modern related research, we believe that static blood blocking collaterals is the initiating factor of this disease, and kidney essence deficiency is the immanent trend of this disease. The pathogenesis and treatment method of this disease are studied on the basis of "soil theory". Guilu Tongqu Decoction is a formula developed by our team based on "soil theory" for the treatment of varicocele infertility. It is a modified version of the classic formula Zuogui Pill , which has the effects of tonifying the kidney, nourishing essence, and promoting blood circulation for removing blood stasis. Its clinical efficacy is good. At the same time, based on our team's extensive clinical practice, we propose three treatment strategies for varicocele infertility, namely, the combination of systemic and local treatment, the combination of radial and symptomatic treatment, and the combination of TCM and surgical procedures. These methods can effectively improve the overall therapeutic effect and provide a reference for the treatment of varicocele infertility with TCM.

Talents are the main force for the development of traditional Chinese medicine（TCM）， and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present， we are still exploring and developing in the fields of the formulation， implementation and evaluation indicators of TCM talent evaluation system. However， there are shortcomings and difficulties. For instance， insufficient stratification in the evaluation， excessive emphasis on the quantity of achievements， neglecting the quality of the achievements and the actual contribution， imperfect assessment indicators， and the weak characteristics of TCM. Therefore， national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard， in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value， ability and contribution. For the evaluation of TCM clinical talents， China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM（CCCL-TCM）， which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry， and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.

Objective:To analyze the influencing factors of skull base reconstruction failure after endoscopic endonasal skull base surgery (EESBS).Methods:A retrospective analysis was performed on 228 EESBS cases at the Affiliated Hospital of Qingdao University from 2018 to 2023. The clinical features associated with skull base reconstruction and postoperative cerebrospinal fluid leakage were collected and analyzed. Lasso regression was initially used for exploratory analysis, and risk factors for reconstruction failure were subsequently evaluated using multifactorial logistic regression.Results:A total of 157 cases of EESBS were included, with an overall reconstruction failure rate of 11.5% (18/157). No patients who underwent second-stage reconstruction with a tipped mucosal flap or multilayered free mucosal and fascial repair experienced further postoperative cerebrospinal fluid leakage. Variables identified through Lasso regression included history of surgery, history of radiotherapy, and site of leakage. Multifactorial logistic analysis showed that history of radiotherapy ( OR=5.96, P=0.021) and site of leakage in the posterior skull base ( OR=8.70, P=0.003) were significant risk factors for failure of skull base reconstruction. Conclusion:In cases with a history of radiotherapy and/or posterior skull base lesions in the operative area, reconstruction strategies should be strengthened to improve the success rate of one-stage repair, in particular, when intraoperative cerebrospinal fluid leakage occurs.

This paper summarized Professor LI Haisong's clinical experience in treating spermatorrhea based on the view of "spirit controlling essence and qi". It is emphasized that the heart spirit has the function of controlling the essence and qi of the human body， believing the frenetic stirring of heart spirit and the insecurity of essence gate are the core pathogenesis of spermatorrhea， LI advocates to regulate the heart spirit first and take into account of the zang-fu organs， essence and qi simultaneously for the treatment. Treatment should be performed according the clinical syndromes differentiatied. For those with heart spirit failing to nourish syndrome， it is recommended to supplement heart qi， nourish spirit and consolidate essence with self-made Yangxin Mijing Formula （养心秘精方）. In case of heart fire hyperactivity， the method of clearing heart heat and draining fire， calming spirit and consolidating essence should be used， and self-made Xiexin Gujing Formula （泻心固精方） is recommended. For heart-liver qi constraint， it is advised to soothe the liver and calm heart， calm the mind and regulate essence with self-made Jieyu Anshen Tiaojing Formula （解郁安神调精方） which is a modifcation to Chaihu Shugan Powder （柴胡疏肝散）. In terms of deficiency of both heart and liver， the treatment principle is supplementing spleen and nourishing heart， calming the mind and controlling essence， for which self-made Xinpi Tongtiao Shejing Formula （心脾同调摄精方） modified from Guipi Decoction （归脾汤） can be used. For deficiency of both heart and kidney， it is better to nourish the kidney and calm heart， calm the mind and consolidate essence with self-made Xinshen Liangzi Tianjing Formula （心肾两滋填精方） that modified from Shuilu Erxian Elixir （水陆二仙丹） and Wuzi Yanzong Pill （五子衍宗丸）. Prescriptions are used to treat the root by harmonizing the zang-fu organs， nourish the spirit by regulating qi and blood， and calm the mind by taking special medi-cinals， and they should be flexibly modified according to the disease.