OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

ObjectiveTo investigate the uric acid-lowering effects and mechanisms of acacetin on hyperuricemia （HUA） in mice. MethodsOteracil potassium and adenine were used to establish the mouse model of HUA. Male Kunming mice （n=48） were randomized into six groups： control， model， low-dose （12.5 mg·kg^-1） acacetin， medium-dose （25 mg·kg^-1） acacetin， high-dose （50 mg·kg^-1） acacetin， and allopurinol （10 mg·kg^-1）. Each group received continuous gavage administration for 21 days. An automatic biochemical analyzer was used to measure the levels of uric acid （UA）， creatinine （Cr）， urea nitrogen （BUN）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. Additionally， the activity of xanthine oxidase （XOD） in the liver and the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the levels of glucose transporter 9 （GLUT9）， urate transporter 1 （URAT1）， phospho-NF-κB p65 （p-NF-κB p65）， and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 （NLRP3） in the renal tissue. ResultsCompared with the control group， the model group showed elevated levels of UA， Cr， BUN， ALT， and AST， increased activity of XOD in the liver（P<0.01）， raised levels of TNF-α， IL-1β and IL-18 in the serum（P<0.01）， and significantly up-regulated expression of GLUT9， URAT1， p-NF-κB p65， and NLRP3 in the renal tissue（P<0.01）. Compared with the model group， acacetin reduced the UA level in a dose-dependent manner， significantly improved liver and kidney functions， decreased the XOD activity in the liver， ameliorated the pathological changes in the renal tissue， down-regulated the expression of GLUT9， URAT1， p-NF-κB p65 and NLRP3 in the renal tissue（P<0.01）， and lowered the levels of TNF-α， IL-1β， and IL-18 in the serum（P<0.01）. ConclusionAcacetin can ameliorate HUA by decreasing uric acid production， increasing uric acid excretion， and inhibiting the NF-κB/NLRP3 signaling pathway. Therefore， acacetin may be a potential drug for the treatment of HUA.

OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

OBJECTIVE To evaluate the cost-utility of benmelstobart combined with anlotinib and chemotherapy as first-line treatment for extensive-stage small cell lung cancer （ES-SCLC） from the perspective of China’s healthcare system. METHODS Based on the data from the ETER 701 study， a partitioned survival model was constructed with a cycle of 3 weeks to simulate the total cost， quality-adjusted life years （QALY）， and incremental cost-effectiveness ratio （ICER） over 10 years for patients with ES- SCLC treated with benmelstobart plus anlotinib and chemotherapy， or chemotherapy alone. One-way sensitivity analysis and probability sensitivity analysis were performed to verify the robustness of the simulation results. The willingness-to-pay （WTP） threshold was set at 3 times the per capita gross domestic product （GDP） of China in 2023， which amounted to 268 074 yuan/QALY. RESULTS Compared with chemotherapy alone， benmelstobart combined with anlotinib and chemotherapy gained 0.438 QALY more at the cost of 403 505.55 yuan more， with an ICER of 922 031.37 yuan/QALY， which was higher than the WTP threshold set in this study. One-way sensitivity analysis showed that benmelstobart’s cost and utility value of the progression-free survival state had a greater impact on the ICER value； probabilistic sensitivity analysis confirmed the robustness of the model； only when the price of benmelstobart was reduced by 75.4%， the combined regimen would be cost-effective. CONCLUSIONS The first-line treatment of ES-SCLC with benmelstobart combined with anlotinib and chemotherapy is not cost-effective from the perspective of China’s healthcare system at present.

OBJECTIVE To evaluate the efficacy， safety and economics of calcium channel modulators in the treatment of diabetic peripheral neuropathic pain （DPNP）， and provide evidence-based evidence for clinical drug selection and decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang data， VIP net， CBM and official websites of foreign health technology assessment （HTA） institutions were systematically searched to collect HTA reports， systematic review/meta-analyses， and pharmacoeconomic studies of pregabalin， gabapentin， crisugabalin， and mirogabalin for the treatment of DPNP. The timeframe for all searches was from the inception to June 2024. After data extraction and quality assessment， the results of the included studies were analyzed descriptively. RESULTS A total of 16 articles were included， involving 1 HTA report， 7 systematic reviews/meta- analyses， and 8 pharmacoeconomic studies. No studies on crisugabalin were retrieved. Compared with placebo， both pregabalin and mirogabalin reduced end point pain scores and increased the proportion of patients with ≥30% and/or ≥50% reduction in pain scores. Pregabalin also improved patient global impression of change （PGIC）. Gabapentin was similar to placebo in reducing end point pain scores and increasing the proportion of patients with ≥30% and/or ≥50% reduction in pain scores， but gabapentin improved PGIC of patients. Compared with pregabalin， mirogabalin was more effective in the treatment of pain. The safety of pregabalin and mirogabalin was similar， and compared with placebo， both pregabalin and mirogabalin increased the risk of common adverse reactions such as dizziness and somnolence. The safety of gabapentin was similar to placebo and duloxetine. Compared with duloxetine， pregabalin and gabapentin were not cost-effective. Compared with gabapentin， pregabalin was cost-effective. Mirogabalin was cost-effective， as compared with placebo and pregabalin. CONCLUSIONS Pregabalin and mirogabalin are effective in the treatment of DPNP， the efficacy of mirogabalin is better than pregabalin， and the safety is similar between them. The economic conclusions vary from country to country， pending a pharmacoeconomic study based on our population.

OBJECTIVE To evaluate the quality of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition， in order to provide the reference for its quality control. METHODS The chemical components in Sendeng-4 were analyzed qualitatively by HPLC-Q-Exactive-MS. The contents of 16 components （methyl gallate， ethyl gallate， epicatechin， dihydromyricetin， genipin-1-O-β-D-gentiobioside， caffeic acid， catechin， corilagin， deacetylasperulosidic acid methyl ester， rutin， geniposide， luteolin， myricetin， quercetin， ferulic acid， and toosendanin） in 15 batches of Sendeng-4 （sample S1-S15） were quantitatively analyzed by HPLC-MS/MS. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares discriminant analysis were conducted and variable importance projection （VIP） value greater than 1 was used as the index to screen the differential components. RESULTS A total of 73 chemical components were identified in Sendeng-4， including 20 flavonoids， 16 tannins， 14 organic acids， etc. According to the quantitative analysis， the results exhibited that the average contentsthe of above 16 components in 15 batches of Sendeng-4 were 3.683-7.730， 2.391-6.952， 2 275.538-4 377.491， 2 699.188-3 537.924， 858.266-1 377.393， 3.366-11.003， 140.624-315.683，414.629-978.334， 285.501-1 510.457， 27.799-48.325， 3 625.415-6 309.563， 0.506-0.656， 442.337-649.283， 47.093-59.736， 12.942-15.822， 127.738-326.649 μg/g， respectively. According to the results of CA and PCA， 15 batches of samples could be clustered into two categories: S1-S3， S5-S6， S9-S10 and S13 were clustered into one category； S4， S7-S8， S11-S12， S14-S15 were clustered into one category. VIP values of geniposide， epicatechin， deacetylasperulosidic acid methyl ester and genipin-1-O- β-D-gentiobioside were all greater than 1. CONCLUSIONS HPLC-Q-Exactive-MS and HPLC-MS/MS techniques are employed for the qualitative and quantitative analysis of Sendeng-4. Through chemical pattern recognition analysis， four differential components are identified: geniposide， epicatechin， deacetylasperulosidic acid methyl ester， and genipin-1-O-β-D-gentiobioside.

OBJECTIVE To evaluate the cost-effectiveness of capecitabine metronomic chemotherapy combined with aromatase inhibitor （AI） versus AI monotherapy as first-line treatment for hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， thereby providing evidence-based support for clinical therapeutic decision- making and healthcare policy formulation. METHODS Based on the MECCA trial， a partitioned survival model was constructed using a 4-week cycle length to simulate outcomes over patients’ lifetime. The model outputs included total costs， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Sensitivity analyses were performed to validate the robustness of base-case results， while scenario analyses examined the cost-effectiveness of both treatment strategies under 10-year， 20-year， and lifetime time horizons. RESULTS With the willingness-to-pay （WTP） threshold set at 1 times China’s 2024 per capita gross domestic product （GDP） （95 749 yuan/QALY）， patients receiving capecitabine metronomic chemotherapy combined with AI regimen gained incremental utility （0.66 QALYs） while incurring higher costs， with ICER of 27 684.85 yuan/QALY. Results of the one-way sensitivity analysis showed that factors with significant impacts on ICER included the cost discount rate， drug costs of the capecitabine metronomic chemotherapy combined with AI group， utility value in the progression-free survival state， follow-up costs， and treatment costs in the subsequent stablephase. Probabilistic sensitivity analysis indicated that when the WTP threshold ≥49 250 yuan/QALY， the capecitabine metronomic chemotherapy combined with AI regimen had a 100% probability of being cost-effective. Scenario analysis results demonstrated that capecitabine metronomic chemotherapy combined with AI regimen was more cost-effective than the AI alone regimen across 10-year， 20-year， and lifetime study horizons. CONCLUSIONS Under the premise that the WTP threshold is set at 1 times China’s per capita GDP in 2024， capecitabine metronomic chemotherapy combined with AI regimen is more cost-effective than the AI alone regimen as the first-line treatment for HR+/HER2－ metastatic breast cancer.