In this study,structural optimization of borneol was carried out to improve their solubility and promote their further application in stroke therapy.BP-3,a prodrug of borneol,was designed and synthesized based on the principle of phosphate modification.The solubility of BP-3 was determined by evaporative light scattering detector(ELSD),and the degree and speed of drug release were tested in mouse plasma,and the neuroprotective effect of BP-3 was evaluated in mouse model of transient middle cerebral artery occlusion(tMCAO).According to the results,BP-3 was completely soluble in saline at 20 mg/mL;in mouse plasma,approximately 40%of the borneol were released within 2 h;in the tMCAO mouse model,TTC staining showed that BP-3 was effective in reducing the infarct area;Nissl staining showed that BP-3 ameliorated the neuronal injury;the grip and grasping strength tests elucidated that BP-3 reduced the damage of sports ability caused by injury;and the rotating rod test proved that BP-3 could promote the recovery of motor ability in mice.BP-3 has good water solubility,suitable drug release rate and excellent neuroprotective effects,and has broad prospects for drug development.

Objective:To analyze the correlation of cyclin-dependent kinase 4 (CDK4) and breast cancer resistance protein (BCRP) expression with pathological features and prognosis of breast cancer.Methods:From Jan. 2020 to Jun. 2021, 132 breast cancer patients admitted to our hospital were chosen. The surgically removed breast cancer tissues and adjacent tissues of all patients were collected, and the expressions of CDK4 and BCRP were detected by immunohistochemical staining. Clinical data of all patients were collected, and the correlation among CDK4, BCRP expression and pathological features, prognosis was analyzed.Results:The positive expression rates of CDK4 and BCRP in breast cancer tissues were higher than those in adjacent tissues ( P <0.05) ; The positive expression rate of CDK4 and BCRP was associated with differentiation degree, TNM stage and lymph node metastasis (all P <0.05) ; Kaplan-Meier analysis showed that the cumulative survival rate of CDK4 and BCRP negative expression group was higher than that of positive expression group ( P <0.05) ; Differentiation degree, TNM stage, lymph node metastasis, CDK4 expression and BCRP expression were independent prognostic factors for overall survival of breast cancer patients (all P <0.05) . Conclusions:CDK4 and BCRP have high positive expression rates in breast cancer tissues, and their expression is related to pathological features, with certain value in evaluating the prognosis of breast cancer patients.

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Humans ; COVID-19 ; Retrospective Studies ; Lung Neoplasms/drug therapy* ; Incidence ; Pneumonia/etiology*

Fibroblast activating protein (FAP) is an important biomarker of cancer associated fibroblasts and activated fibroblasts, which is highly expressed in activated fibroblasts of many tumor and fibrotic tissues, but not in normal tissues and non malignant lesions. Therefore, FAP has become an excellent target for diagnosis and treatment of tumors and other diseases. PET imaging and internal radiotherapy based on FAP inhibitor (FAPI) have been used in the diagnosis and treatment of many diseases, such as cancer and fibrosis. We first introduce the mechanism of disease occurrence and progression mediated by FAP and its clinical significance as a therapeutic target.Then,we systematically summarize the FAP probes labeled with 125I, 68Ga, 64Cu and other radionuclides, including their structural evolution, imaging, biodistribution and pharmacokinetic properties.After that, the reported strategies to improve the pharmacokinetic properties and target affinity of probes are summarized, including the use of squaramide linkers,modification with albumin binding agent,the development of dual-targeting probes.Finally, some suggestions for the future development of novel radioactive probes targeting FAP and the clinical application of classical probes are proposed.

[摘 要] 目的：探索南蛇藤提取物齐墩果烷型五环三萜（28-hydroxy-3-oxoolean-12-en-2-oic acid）协同miR-451对人胃癌AGS细胞增殖、迁移的影响及其可能的分子机制。方法：用miR-451过表达慢病毒感染AGS细胞，并用盐酸多西环素（DOX）10或100 ng/ml诱导24 h，构建过表达miR-451的细胞AGS/miR-451+。采用10、20、40、80、160 μmol/L的齐墩果烷型五环三萜处理AGS/miR-451+细胞，MTT法、划痕实验分别检测细胞增殖和迁移能力的变化，WB法检测细胞中mTOR通路及凋亡相关蛋白表达水平的变化。结果：成功构建过表达miR-451的AGS/miR-451+细胞。与未加药对照组相比，齐墩果烷型五环三萜处理后AGS/miR-451+细胞的增殖抑制率均呈时间和浓度依赖性升高（P<0.05或P<0.01），细胞迁移率均显著降低（P<0.05或P<0.01）。齐墩果烷型五环三萜处理组细胞中，mTOR 信号通路相关蛋白的表达量均有所降低（P<0.05或P<0.01）；凋亡相关蛋白中，Bcl2的表达量下降，BAX、caspase-3、caspase-1及细胞色素c的表达量升高（P<0.05或P<0.01）。结论：齐墩果烷型五环三萜能够协同miR-451抑制人胃癌AGS细胞的增殖与迁移，其机制可能与影响凋亡和mTOR信号通路相关蛋白的表达有关。

Objective:To understand the utilization of clinical services provided through hospital-at-home to the elderly in Xuzhou City, and analyze patient satisfaction.Methods:The stratified cluster sampling method was used to select community elderly people aged 60 and above in Xuzhou city to conduct a face-to-face questionnaire survey.Descriptive analysis was used to examine the utilization and evaluation of home-based clinical services for the elderly.Multiple linear regression analysis was used to analyze associated factors for the satisfaction of the elderly in this care setting.Results:A total of 203 elderly people who had received this type of services were investigated.The overall satisfaction of the elderly in Xuzhou City with home-based clinical services was 79.3%(161/203), and the average satisfaction score of the comprehensive evaluation was(4.11±1.03)points.Age( β=-0.011), marital status( β=0.164), informed consent for service( β=0.162), doctors' bed-side services( β=0.146), service fee( β=0.346), and the home hospital bed assembling process( β=0.257)were the influencing factors for satisfaction with family hospital bed services, according to the patients involved in the comprehensive evaluation(all P<0.05). Conclusions:The utilization and evaluation with clinical services by elderly people in the hospital-at-home setting in downtown Xuzhou is relatively good, with relatively high satisfaction.Comprehensive measures should be taken in response to factors related to satisfaction to promote sustainable development of clinical services through hospital-at-home in China.

Objective: To explore the impact of insulin resistance (IR) and adiponectin (APN) lacking on myocardial remodeling in experimental mice. Methods:16 normal C57 mice were divided into 2 groups: Control group and IR group; in addition, 16 APN gene knockout(APNKO) mice were divided into another 2 groups: APNKO group and APNKO+IR group.n=8 in each group. The mice in Control group and APNKO group were fed with normal diet, in IR group and APNKO+IR group were fed with high fat diet to create the IR model. All animals were treated for 12 weeks. Blood levels of total cholesterol(TC), triglycerides(TG),fasting plasma glucose(FPG) and fasting insulin(FINS) were examined; heart weight and left ventricular weight were measured; left ventricular myocardial morphological changes and the degree of ifbrosis were assessed by HE staining and Masson staining; protein expressions of myocardial matrix metalloproteinase-9 (MMP-9) and APN were detected by immunehistochemistry and Western blot analysis. Results: Compared with Control group, IR group, APNKO group and APNKO+IR group showed elevated blood levels of TC, TG, FPG and FINS; increased heart weight and left ventricular weight, allP<0.05; IR group, APNKO group and APNKO+IR group presented more myocardial hypertrophy, decreased protein expression of APN and increased protein expression of MMP-9, allP<0.05.Conclusion: IR and APN lacking could incur myocardial remodeling in experimental mice and they had synergistically facilitated effect.

Objective: To investigate the clinical manifestation, cytogenetics, gene mutations and prognostic factors of chronic neutrophilic leukemia (CNL) . Methods: 16 CNL cases, according to WHO (2016) -definition, were reviewed retrospectively. Identifications of the CSF3R, ASXL1, SETBP1, CALR and MPL mutations were performed by direct sequencing. JAK2 V617F mutation was detected by AS-PCR. Results: Of the 16 CNL patients, the median age was 64 (43-80) years with a male predominance of 75% (12/16) . The median hemoglobin was 114 (81-154) g/L, with median WBC of 41.20 (26.05-167.70) (10⁹/L and median PLT of 238 (91-394) ×10⁹/L.The median level of marrow fibrosis (MF) was 1 (0-3) degree. There was no other cytogenetic abnormalities except t (1;7) (p32;q11) , +21 and 14ps+ for each. All the 16 CNL patients harbored CSF3R T618I mutation. ASXL1 mutations were identified in 81% (13/16) , while SETBP1 mutations were confirmed in 63% (10/16) . The CALR K385fs*47 mutation was found. There was no mutation in JAK2 V617F or MPL in the above 16 patients. The median overall survival (OS) of patients presented with WBC≥50×10⁹/L at diagnosis (11 months) was significantly shorter than of WBC<50×10⁹/L (39 months, P=0.005) . Conclusion CSF3R T618I mutation was specific for CNL. The median OS of CNL patients was 24 months, and WBC≥50×10⁹/L at diagnosis was an unfavorable prognostic factor.

Objective To observe the effect of connect meridians inducing Yin from Yang on muscle-tension after cerebral infarction. Methods 82 patients with cerebral infarction in Second Hospital of Harbin from 2010 to 2014 were divided into observation group (n=41) and control group (n=41) according to hospitalization order. The observation group accepted acupuncture of connecting meridians inducing Yin from Yang, and the control group accepted the traditional acupuncture method for 2 weeks. The situation of spasticity, the motor limb function of limbs, and activities of daily living were evaluated with modified Ashworth Scale (MAS), Clinic Spasticity Index (CSI), Fugl-Meyer Assessment (FMA) and Barthel index (BI), respectively. Results Compared with the control group, the score of MAS decreased (t=2.212, P=0.030), the score of CSI decreased (t=2.514, P=0.014), the score of FMA increased (t=4.288, P<0.001), and the score of BI in-creased (t=2.970, P=0.004) in the observation group after treatment. Conclusion The acupuncture of connecting meridians inducing Yin from Yang can reduce the muscle-tension of limbs, improve the motor function and increase the activities of daily living.

Objective To understand the changes of schistosomiasis epidemic situation,so as to provide the evidence for for?mulating schistosomiasis control strategy in the Hexi reservoir area. Methods From 2012 to 2015,Xinyuan Village,Meishan Town in the north entrance of Hexi reservoir was selected as a monitoring site. According to the requirements of the monitoring program of schistosomiasis surveillance in Zhejiang Province,the Schistosoma japonicum infection was investigated by using the serological screening(IHA),and the basic situation of the surveillance site was also investigated. Results From 2012 to 2015,167 environments(21.68 hm2)were surveyed,and 2 slices(0.1 hm2)were found with Oncomelania hupensis snails. The detection rate of frames with snails was 0.12%,and the living snail density was 0.0192 snails per 0.1 m2. Totally 374 snails were dissected and no schistosome infected snails were found. A total of 970 local residents and 8 748 mobile people were investigated with the serological tests,and no schistosome infected people were found. In addition,3 085 cattle were investigated and no in?fected ones were found. Conclusion The schistosomiasis epidemic situation is stable in the Hexi reservoir area,but we still should strengthen the monitoring of imported source of infection and snail status,and increase the efforts of environmental trans?formation.