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.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To understand the current status of gastroscopy in diagnosing gastric lesions in general population, and to recommend the optimal age for the first gastroscopy and intervals for repeated gastroscopy.Methods:The gastroscopy records of residents aged 18-80 years in Yinzhou District of Ningbo, Zhejiang Province, between April 2010 and December 2021 were analyzed retrospectively. The detections of gastric lesions across different years, age and genders were described. Goodness of fit tests were applied to compare the differences in detection rates of different lesions in first-time endoscopy in different age groups and different populations. Generalized additive models were used to fit the trend of age specific gastric lesion detection rate explore the optimal age for gastroscopy. The appropriate gastroscopy intervals were determined according to the progress of the gastric lesions detected in repeated gastroscopy.Results:A total of 237 751 participants with 344 398 gastroscopy records were included in analyses. A total of 5 597 cases of chronic atrophic gastritis (CAG), 9 796 cases of intestinal metaplasia (IM), 165 cases of low-grade intraepithelial neoplasia (LGIN), 52 cases of high-grade intraepithelial neoplasia (HGIN) and 435 cases of gastric cancer were detected by the first gastroscopy. The overall detection rate of gastric lesions increased significantly in age group 45-70 years, and remained stable after 70 years old, with LGIN and HGIN showing notable increases at 50 and 55 years old, respectively. Repeated gastroscopy detected CAG, IM, LGIN, and HGIN at a higher rate compared with the first gastroscopy. Normal/superficial gastritis progressed in 3-5 years, whereas CAG or more severe lesions progressed in 1-6 years.Conclusion:Gastroscopy is recommended for general population aged 45 years and above. Furthermore, gastroscopy can be performed every 3-5 years for individuals with normal endoscopy results and once a year for patients with CAG or more severe gastric lesions.

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.

Objective:To investigate the expression of the novel immune checkpoint SIGLEC9 and SIGLEC9+T cells in cervical cancer and its clinical correlation.Methods:A total of 132 paraffin-embedded specimens of cervical tissue from patients with cervical cancer who under-went surgical treatment or pathological biopsy at The First Affiliated Hospital of Xinjiang Medical University from May 2022 to October 2023 were included for study.In addition,58 paraffin-embedded specimens of normal cervical tissue from patients with benign uterine leiomyomas who underwent total uterine excision during the same period were selected as normal controls.Furthermore,108 peripheral blood samples from patients with cervical cancer who underwent surgical treatment or pathological biopsy were collected for study,and 86 peripheral blood samples from healthy individuals during the same time period were selected as controls.Bioinformatics technology,im-munohistochemical(IHC)staining,flow cytometry,and double immunofluorescence(IF)staining were used to assess the expression of SIGLEC9 and SIGLEC9+T cells in cervical cancer,followed by correlation analysis with clinical indicators.Results:The bioinformatics,IHC,and double IF staining results showed that SIGLEC9 and SIGLEC9+T cells were highly expressed in cervical cancer tissues(P<0.05).The flow cyto-metry results showed that SIGLEC9+CD4+T and SIGLEC9+CD8+T cells were increased in the peripheral blood of patients with cervical cancer(P<0.05).SIGLEC9 expression correlated with tumor size,FIGO stage,lymph node metastasis,and human papillomavirus(HPV)infection(P<0.05).Conclusions:The novel immune checkpoint SIGLEC9 was highly expressed in cervical cancer tissues,and SIGLEC9+T cells infiltrated cervical cancer tissues.In vitro cell experiments showed that SIGLEC9 affects T cell function.In summary,SIGLEC9 provides a novel research direction for understanding the immune escape mechanism of cervical cancer and a novel therapeutic target for cervical cancer immuno-therapy.

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 explore expression of Siglec-7 on monocytes in peripheral blood of patients with brucellosis and cor-relation between Siglec-7+monocytes and Th1/Th2 cells,and to analyze clinical significance of Siglec-7 molecule in patients with bru-cellosis.Methods:Fifty patients with newly diagnosed Brucella infection(BI group)and 46 healthy controls(control group)were in-cluded.Flow cytometry was used to detect expression of Siglec-7 on monocytes,and correlation between Siglec-7+monocytes and clini-cal indicators of patients with brucellosis were analyzed.Flow cytometry was used to detect Th1/Th2 cells levels,and CBA method was used to detect IFN-γ and IL-4 in peripheral serum.Correlation between Siglec-7+monocytes and Th1/Th2 cells,IFN-γ/IL-4 were ana-lyzed.Results:Siglec-7+monocytes level in BI group was significantly higher than that in control group(P<0.001);Siglec-7+mono-cytes level in patients with abnormal liver function and lung X-ray were higher than those in patients with normal liver function and lung X-ray(P<0.001,P<0.05);Compared with control group,Th2 cell and IL-4 levels were significantly increased(P<0.05),while Th1 cells and IFN-γ levels were significantly reduced(P<0.001);Th1/Th2 and IFN-γ/IL-4 were also significantly reduced(P<0.001).Siglec-7+monocyte level was negatively correlated with Th1 and IFN-γ(r=-0.651,r=-0.407),while was positively correlated with Th2 and IL-4(r=0.706,r=0.530).Conclusion:During Brucella infection,increased percentage of Siglec-7+monocytes may be involved in Th1/Th2 cell imbalance.

Hyperlipidaemic rats were randomly divided into a model group,a total flavonoids from echinops latifolius tausch(TFET)high,medium and low dose group,and a positive control group;meanwhile,healthy rats were selected as a blank control group.The rats in each group were dosed with the corresponding concentrations of TFET,simvastatin and distilled water for 45 consecutive days,and were tested for relevant lipid biochemical indexes,antioxidant indexes and PPARα path-way-related gene expression.The results showed that high-dose TFET could reduce the concentra-tions of TC,TG and LDL-C and increase the concentration of HDL-C very significantly;medium-dose TFET could reduce the concentrations of TC and TG very significantly and reduce the con-centration of LDL-C significantly;and low-dose TFET could reduce the concentrations of TC and LDL-C significantly.High,medium and low doses of TFET can extremely significantly reduce in-crease SOD activity;high and medium doses of TFET can extremely significantly reduce MDA content;high dose of TFET can extremely significantly increase T-AOC activity.The high dose of TFET could extremely significantly increase the expression of PPARα,CYP7A1 and CPT-1 genes in rat liver;the medium dose of TFET could extremely significantly increase the expression of CYP7A1 and CPT-1 genes,and could significantly increase the expression of PPARα gene;the low dose of TFET could extremely significantly increase the expression of CYP7A1 gene,and signifi-cantly increase the CPT-1 gene expression.The results suggest that TFET has antioxidant and lip-id-lowering effects on hyperlipidaemic rats,and its mechanism may be related to the activation of PPARα and its downstream related genes to promote fatty acid β-oxidation.

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.

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.