[摘 要] 目的：探讨透明质酸介导运动受体（HMMR）在食管鳞状细胞癌（ESCC）细胞恶性进展中的作用及其潜在的分子机制。方法：收集2018年1月至2020年12月期间在河北医科大学第四医院手术切除的8例ESCC组织及癌旁组织标本，以及ESCC细胞KYSE-30和KYSE-150。利用WB法和免疫组化（IHC）法检测HMMR在ESCC组织中的表达情况。采用RNA干扰技术，在KYSE-30和KYSE-150细胞中敲低HMMR表达，qPCR法和WB法检测敲低效果，通过CCK-8实验和Transwell实验分别检测敲低HMMR对ESCC细胞增殖和侵袭能力的影响。4-硝基喹啉1-氧化物（4NQO）诱导小鼠致癌建立ESCC模型，H-E染色观察食管的形态变化，IHC法分析HMMR、序列相似性家族83成员D（FAM83D）、上皮钙黏素（E-cadherin）和神经钙黏素（N-cadherin）在小鼠不同癌变程度组织中的表达情况。结果：人ESCC组织中HMMR表达水平显著高于癌旁组织（均P < 0.05）。敲低HMMR后，KYSE-30和KYSE-150细胞的增殖和侵袭能力均显著降低（P < 0.05或P < 0.01），同时降低了FAM83D的表达水平（均P < 0.01）。裸鼠成瘤实验中，4NQO组小鼠体质量均低于对照组（均P < 0.05）；IHC法染色结果显示，肿瘤组织中HMMR呈高表达（P < 0.05），其中在高级别上皮内瘤变（HGIN）组织中的表达显著高于低级别上皮内瘤变（LGIN）组织（P < 0.001）。HMMR与FAM83D、N-cadherin表达呈显著正相关（r = 0.724、0.870，均P < 0.001），与E-cadherin表达呈显著负相关（r = -0.714，P < 0.001）。结论：HMMR在ESCC组织中呈高表达，其可能通过上调FAM83D表达水平促进ESCC的进展。

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

Objective:To explore the application value of real-time shear wave elastography(SWE)and ultrafast pulse wave velocity(UFPWV)techniques in assessing carotid artery stiffness of patients with gouty arthritis(GA).Methods:A total of 80 GA patients admitted to the First People's Hospital of Yibin from August 2022 to July 2023 were selected as GA group.Among of them,24 cases combined with bone erosion who were confirmed by imaging examination,and 56 cases did not combine with bone erosion.In addition,a total of 40 healthy individuals,who underwent physical examinations in our hospital during the same period,were selected as the healthy control group.SWE and UFPWV were used to detect the maximum,minimum and mean values of Young's modulus values of the vessel wall of common carotid artery,and the pulse wave velocity at the beginning of systole(PWVBS)and pulse wave velocity at the end of systole(PWVES)of the vessel wall of common carotid artery of all subjects,and to assess the hardness of circumferential and longitudinal vessel wall of common carotid artery of them.The differences in Young's modulus values,PWVBS and PWVES between two groups were compared.And then,the correlations between bone erosion and Young's modulus values,PWVBS,PWVES of GA patients were further analyzed.Results:The maximum,minimum,mean values,PWVBS and PWVES in the GA group were respectively(78.80±12.38)kPa,(57.83±7.42)kPa,(67.67±8.38)kPa,(7.06±0.59)m/s and(9.50±0.63)m/s,which were significantly higher than those in the healthy control group(t=11.066,8.216,11.751,14.159,19.118,P＜0.05).The maximum,minimum,mean values,PWVBS and PWVES of GA patients with bone erosion were respectively(82.95±6.37)kPa,(59.59±5.29)kPa,(72.18±7.62)kPa,(7.37±0.43)m/s,(10.43±0.47)m/s,which were significantly higher than those[(77.01±5.32)kPa,(57.08±4.73)kPa,(65.73±4.54)kPa,(6.92±0.39)m/s and(9.10±0.41)m/s]of GA patients without bone erosion,the differences were significant(t=4.309,2.099,4.699,4.586,12.720,P＜0.05).Spearman correlation analysis showed that there was significant correlations between maximum,minimum,mean values,PWVBS,PWVES and the combined bone erosion in GA patients(r=0.602,0.421,0.682,0.647,0.732,P＜0.05).Conclusion:SWE and UFPEV techniques can evaluate the hardness of vascular wall of GA patients,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient is higher than that of healthy person,and the hardness of circumferential and longitudinal vessel wall of common carotid artery of GA patient with bone erosion is higher.

Background::Whether the dynamic weight change is an independent risk factor for mortality remains controversial. This study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial (NIT) cohort.Methods::Body weight of 21,028 healthy residents of Linxian, Henan province, aged 40-69 years was measured two times from 1986 to 1991. Outcome events were prospectively collected up to 2016. Weight maintenance group (weight change <2 kg) or stable normal weight group was treated as the reference. Cox proportional hazard model was performed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the risk of mortality.Results::A total of 21,028 subjects were included in the final analysis. Compared with the weight maintenance group, subjects with weight loss ≥2 kg had an increased risk of death from all-cause (HR All-cause = 1.14, 95% CI: 1.09-1.19, P <0.001), cancer (HR Cancer = 1.12, 95% CI: 1.03-1.21, P = 0.009), and heart disease (HR Heart diseases = 1.21, 95% CI: 1.11-1.31, P <0.001), whereas subjects with weight gain ≥5 kg had 11% (HR Cancer = 0.89, 95% CI: 0.79-0.99, P = 0.033) lower risk of cancer mortality and 23% higher risk of stroke mortality (HR Stroke = 1.23,95% CI: 1.12-1.34, P <0.001). For the change of weight status, both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death (HR Overweight to normal = 1.18, 95% CI: 1.09-1.27; HR Becoming underweight = 1.35, 95% CI: 1.25-1.46) and cancer death (HR Overweight to normal = 1.20, 95% CI: 1.04-1.39; HR Becoming underweight = 1.44, 95% CI: 1.24-1.67), while stable overweight could increase the risk of total death (HR Stable overweight = 1.11, 95% CI: 1.05-1.17) and death from stroke (HR Stable overweight = 1.44, 95% CI: 1.33-1.56). Interaction effects were observed between age and weight change on cancer mortality, as well as between baseline BMI and weight change on all-cause, heart disease, and stroke mortality (all Pinteraction <0.01). Conclusions::Weight loss was associated with an increased risk of all-cause, cancer, and heart disease mortality, whereas excessive weight gain and stable overweight were associated with a higher risk of stroke mortality. Efforts of weight management should be taken to improve health status.Trial registration::https://classic.clinicaltrials.gov/, NCT00342654.

AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.

Objective To predict the constitutive parameters of a superelastic model of plantar soft tissues based on random forest(RF)and backpropagation(BP)neural network algorithms to improve the efficiency and accuracy of the method for obtaining constitutive parameters.Methods First,a finite element model for a spherical indentation experiment of plantar soft tissues was established,and the spherical indentation experiment process was simulated to obtain a dataset of nonlinear displacement and indentation force,divided into training and testing sets.The established RF and BP neural network(BPNN)models were trained separately.The constitutive parameters of plantar soft tissues were predicted using experimental data.Finally,the mean square error(MSE)and coefficient of determination(R2)were introduced to evaluate the accuracy of the model prediction,and the effectiveness of the model was verified by comparison with the experimental curves.Results Combining the RF and BPNN models with finite element simulation was an effective and accurate method for determining the superelastic constitutive parameters of plantar soft tissues.After training,the MSE of the RF model reached 1.370 2×10-3,and R2 was 0.982 9,whereas the MSE of the BPNN model reached 4.858 1×10-5,and R2 was 0.999 3.The inverse-determined constitutive parameters of the plantar soft tissues suitable for simulation were obtained.The calculated response curves for the two predicted sets of constitutive parameters were in good agreement with the experimental curves.Conclusions The prediction accuracy for the superelastic constitutive parameters of plantar soft tissues based on an artificial intelligence algorithm model is high,and the relevant research results can be applied to study other mechanical properties of plantar soft tissues.This study provides a new method for obtaining the constitutive parameters of plantar soft tissues and helps to quickly diagnose clinical problems,such as plantar soft tissue lesions.

Abstract： Objective　To analyze the epidemic situation and risk factors of schistosomiasis in Hubei Province from 2015 to 2022, and to provide a scientific basis for the goal of all schistosomiasis-endemic counties in the province reaching the elimination standard by 2030. Methods　According to the requirements of the National Schistosomiasis Surveillance Plan (2014 edition) and National Schistosomiasis Surveillance Plan (2020 edition), the snail situation and the risk of wild fecal transmission, along with regional distribution in schistosomiasis endemic areas in Hubei Province from 2015 to 2022 were analyzed and the risk was rated. Results　From 2015 to 2022, a total of 60 203 risk monitoring environments per time was carried out, with 10 223 460 frames of snails inspected, capturing 2 344 094 snails, among which 1 357 479 live snails, and an average density ranging from 0.07-0.29 snails/0.11 m2. In 2015 and 2017, 11 and 3 schistosomiasis-infected snails were detected respectively, corresponding to 3 and 2 positive snail environments. The proportion of wild feces distribution environment in the total monitoring environment showed a downward trend, with cow dung accounting for the highest proportion (69.27%). A total of 19 549 wild feces were collected, of which 78 were positive for schistosomiasis. Since 2018, only one positive cow dung was found in 2019, and none in other years. From 2015 to 2020, the density of live snails and the proportion of wild feces in the monitoring environment in each risk monitoring county (city, district) had significantly reduced, with areas of higher snail density such as Gongan County, Yangxin County with higher density of live snails decreasing to below 1 per 0.11 m2 from 2017. Among the 60 203 risk monitoring environments, 53 were identified as GradeⅠrisk (not detected since 2020), 1 999 as GradeⅡrisk, and 58 030 as GradeⅢrisk. Conclusions　From 2015 to 2022, the overall schistosomiasis epidemic in Hubei Province showed a downward trend. However, the risk of schistosomiasis transmission still exists in some areas. In the future, we should continue to strengthen the epidemic monitoring in key areas, improve the sensitivity and level of monitoring, and prevent the rebound of the epidemic.

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.