Nasopharyngeal carcinoma （NPC） is a malignant tumor originating from the mucosal epithelium of the nasopharynx. In recent years， its incidence and mortality rates have shown a continuous upward trend， and there is still a lack of therapeutic regimens with both favorable efficacy and safety in clinical practice. Mitogen-activated protein kinase （MAPK） signaling pathway plays a key regulatory role in biological processes such as cell proliferation， differentiation， apoptosis and invasion. It is widely involved in the occurrence and progression of NPC， and serves as an important target in the research field of anti-NPC therapy. This article systematically elaborates on the mechanism of action of the MAPK signaling pathway in NPC， and reviews the research status regarding the anti-NPC effect of active components of traditional Chinese medicine （TCM） and TCM compound prescriptions by regulating this signaling pathway. The results show that TCM active components， including flavonoids （luteolin， maackiain， baicalein， etc.）， alkaloids （picrasidine Ⅰ， tetrandrine， etc.）， terpenoids （bakuchiol， cantharidic acid）， as well as traditional Chinese medicine compound formulas （such as Biyan jiedu capsules and Yiqi jiedu formula） can exert effects including inducing autophagy and apoptosis of NPC cells， promoting pyroptosis， reversing drug resistance， blocking epithelial-mesenchymal transition， weakening cell stemness and arresting cell cycle progression by regulating the MAPK signaling pathway， thereby inhibiting the occurrence and development of NPC through multiple pathways.

The frequent extreme climatic events post multifaceted impacts on the distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum in the context of global climate change. This article systematically reviews the effects of four types of extreme climatic events, including floods, droughts, heat waves, and cold waves, on the survival, reproduction, and distribution of Oncomelania hupensis. Floods may expand suitable snail habitats, and increase both emerging and re-emerging snail habitats; however, the impact of floods on O. hupensis density is characterized by a lag effect of a decline followed by a rise. Droughts may cause fragmentation of suitable O. hupensis snail habitats, reduced O. hupensis snail egg production rates, and increased O. hupensis snail mortality, and heat waves may cause an increase in O. hupensis snail mortality, a reduction in numbers of O. hupensis snail populations and shrinking of O. hupensis snail distribution, while cold waves may cause a reduction in O. hupensis snail density and a rise in O. hupensis snail mortality. Extreme climate events pose both shortand long-term effects on the distribution of O. hupensis. Intensified surveillance of O. hupensis snails is required in high-risk environments.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective To assess the survival vulnerability of Oncomelania hupensis in Jiangxi Province under future climate scenarios, and to identify low-vulnerability areas for its survival in this province. Methods Village-level O. hupensis snail survey and O. hupensis snail control with chemical treatments in Jiangxi Province from 2016 to 2024 were captured from the Parasitic Disease Prevention and Control Information Management System of China Disease Prevention and Control Information System. Climatic data were primarily sourced from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), including annual average temperature, annual average precipitation, annual accumulated temperature above 10 °C, annual accumulated temperature above 0 °C, annual maximum temperature, annual minimum temperature, and annual average relative humidity, and nineteen bioclimatic variables were downloaded from the WorldClim website (https://www.worldclim.org/), including mean diurnal range, isothermality, temperature seasonality, and so on. Elevation and normalized difference vegetation index were catprued from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), and distance to rivers was downloaded from the WorldPop website (http://www.worldpop.org), and land use and land cover (LULC) data were downloaded from the Big Earth Data Center, Chinese Academy of Sciences (https://data.casearth.cn/), and nature reserve data were obtained from the China Nature Reserve Specimen Resource Sharing Platform (http://www.papc.cn/). Three Shared Socioeconomic Pathways (SSPs) from the Beijing Climate Center-Climate System Model version 2-Medium Resolution (BCC-CSM2-MR) global climate model were employed as future climate scenarios, including SSP126, SSP245, SSP585, and the biomod2 ensemble model in R package was used to simulate suitable habitats for O. hupensis snails in Jiangxi Province in 2050 and 2070 under these scenarios. A snail survival vulnerability index was constructed based on the area of suitable snail habitats, area covered by snail control through chemical treatment, area covered by nature reserves, and changes in snail habitat fragmentation, and a map of snail survival vulnerability distribution was plotted. Results The real area of snail habitats ranged from 78 486.76 to 85 309.47 hm², and the area of snail control with chemical treatment ranged from 10 138.98 to 13 240.16 hm² in Jiangxi Province from 2016 to 2024. There were 429 to 531 villages detected with snails during the nine-year period, and the number of actually snail-infested villages ranged from 645 to 686. A total of 818 snail-present points and 1 996 snail-absent points were obtained from snail survey records. The best performance of the biomod2 ensemble model was achieved if a weighted mean approach was used as the ensemble strategy, with a true skill statistic value of 0.799 and an area under the receiver operating characteristic curve of 0.957, and modeling identified annual average relative humidity and annual average precipitation as two most influencing climatic variables for snail distribution. Relative to the current areas of suitable snail habitats under present climate conditions, the area of suitable snail habitats was projected to expand by 24.49% to 46.28% in Jiangxi Province under future climate scenarios, and the proportion of nature reserves areas in the areas of suitable snail habitats was projected to decrease slightly from the current 2.77% to approximately 2.52%, while the proportion of areas of snail control through chemical treatment in areas of suitable snail habitats varied from 0.64% to 19.57%, and the percentage of changes in snail habitat fragmentation ranged from 3.86% to 12.23%. Based on these four indicators, the snail survival vulnerability index was estimated to range from –1.96 to 0.62 in Jiangxi Province. The arithmetic mean of the snail survival vulnerability index differed under three SSP scenarios (SSP126, SSP245 and SSP585), with the highest mean value (–0.69) in 2070 under SSP126, and the lowest mean value (–0.78) in 2070 under SSP585. Conclusions The snail survival vulnerability index ranges from –1.96 to 0.62 in Jiangxi Province under future climate scenarios, and the suitable habitats for O. hupensis snails appear an overall tendency towards expansion. Low-vulnerability snail habitats are mainly distributed along the shores of Poyang Lake and the Yangtze River in Jiangxi Province, partially overlapping with nature reserves. Intensified surveillance of O. hupensis snails is recommended in these areas in the future.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Objective:To explore the effects of Xiaoyao Conger Decoction pretreatment on model rats of tinnitus with syndrome of liver-qi stagnation and spleen deficiency (TLSSD) and its preliminary mechanisms.Methods:The rats were divided into four groups: a blank group, a model group, a positive group, and Xiaoyao Conger high- and low-dosage groups, with 7 rats in each group according to random number table method. Except for the blank group, the TLSSD model was prepared by the composite etiological method in all groups of rats. The positive group received a gavage of carbamazepine at 15 mg/kg, while Xiaoyao Conger high- and low-dosage groups were given 30 g/kg and 15 g/kg of Xiaoyao Conger Decoction, respectively. The blank and model groups were administered an equal volume of saline once daily for 4 weeks. The frequency of conditioned avoidance response behaviors in rats was recorded before and at 2 and 4 weeks post-drug administration; TCM syndrome scores were documented before and after treatment; auditory brainstem response (ABR) thresholds were monitored at frequencies of 4, 12, 20, and 28 kHz; IL-1β mRNA expression in the inferior colliculus and cochlea was detected by RT-qPCR; and the levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hippocampal tissues were determined by LC-MS/MS.Results:The model group exhibited symptoms of liver depression, including irritability, yellow fur, and a dark red tongue, along with signs of spleen deficiency such as lethargy, decreased activity, and loose stools. Compared to the model group, rats in the Xiaoyao Conger high- and low-dosage groups demonstrated a reduction in conditioned avoidance response behaviors ( P<0.05 or P<0.01), a decrease in TCM syndrome scores ( P<0.05 or P<0.01), lower ABR thresholds at 12, 20, and 28 kHz ( P<0.01), reduced levels of IL-1β mRNA in the inferior colliculus and cochlea ( P<0.05 or P<0.01), and decreased hippocampal Glu levels ( P<0.01). Conclusion:The therapeutic effect of Xiaoyao Conger Decoction pretreatment on TLSSD rats may be related to its ability to improve the mood disorders and stress, reduce the neuroinflammatory response, regulate the CNS neurotransmitter balance, and correct the overexcitability of the auditory centre, etc.

Objective To explore the effect of saururus chinensis tannin on proliferation and mi-gration of non-small cell lung cancer(NSCLC)cells by regulating Hippo/YAP signaling pathway.Methods Human NSCLC cell line A549 was treated with different concentrations of saururus chinen-sis tannin.Cell viability was detected by CCK-8 assay to screen appropriate drug concentrations.NSCLC cells were randomly divided into control group,low-concentration saururus chinensis tannin group,medium-concentration saururus chinensis tannin group,high-concentration saururus chinensis tannin group and high-concentration saururus chinensis tannin+YAP activator(XMU-MP-1)group.Cell viability,colony formation capacity,migration ability and invasion ability were evaluated using the CCK-8 assay,plate colony formation assay,wound healing assay and transwell assay,respective-ly.Expression levels of proteins associated with migration and invasion[E-cadherin,N-cadherin and snail]and proteins related to the Hippo/YAP signaling pathway[Yes-associated protein(YAP),phosphorylated Yes-associated protein(p-YAP),connective tissue growth factor(CTGF)and cys-teine-rich angiogenic inducer 61(CYR61)]were detected by western blot analysis.Results Com-pared with the control group,the cell viability,the number of colony cells,migration and invasion abilities,as well as the expression levels of N-cadherin,snail,YAP,CTGF and CYR61 proteins in the low-concentration saururus chinensis tannin group,medium-concentration saururus chinensis tannin group and high-concentration saururus chinensis tannin group were significantly decreased or reduced,and the expression levels of E-cadherin and p-YAP proteins were significantly increased(P＜0.05),with the most pronounced effects observed in the high-concentration saururus chinensis tannin group.Compared with the high-concentration saururus chinensis tannin group,the cell viabil-ity,the number of colony cells,migration and invasion abilities,as well as the expression levels of N-cadherin,snail,YAP,CTGF and CYR61 in the high-concentration saururus chinensis tannin+YAP activator group were significantly increased or enhanced,while the expression levels of E-cad-herin and p-YAP were significantly decreased(P＜0.05).Conclusion Saururus chinensis tannin may reduce the survival rate of NSCLC cells and inhibit their proliferation,migration and invasion a-bilities by regulating the Hippo/YAP signaling pathway.

Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.