Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Space radiation is the most important environmental harmful factor in long-term manned spaceflight and deep space exploration, and it may produce deterministic and stochastic effects on tissues and organs. In-depth research into the biological effects, mechanisms, and protective measures of space radiation is essential and serves as an important foundation for exploring radiation biology and promoting major manned space projects. Firstly, this review introduces the spatiotemporal distribution characteristics of space radiation during low-earth orbit flights, manned lunar landings, and deep space exploration missions, as well as the health risks and challenges it posed to astronauts. Then, it discusses medical requirements and exposure limits, risk assessment, and protection technologies included in the space radiation protection system established internationally and over 30 years of Chinese manned spaceflight departments. Finally, it outlines the subsequent work and prospects for further research.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Objective To investigate the value of combined detection of serum interleukin-25(IL-25),interleukin-33(IL-33),C-C motif chemokine ligand 2(CCL-2)and C-C motif chemokine ligand 17(CCL-17)in children with bronchial asthma.Methods A total of 91 children diagnosed with bronchial asthma were enrolled into asthma group,and 46 healthy children undergoing routine physical examinations during the same period were included in control group.General clinical data,airway inflammatory markers[fractional exhaled nitric oxide(FeNO)and immunoglobulin E(IgE)]and pulmonary function parameters[forced vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),minute resting ventilation(VE)and specific airway resistance(Raw)]were comparedbetween the two groups.The levels of serum IL-25,IL-33,CCL-2 and CCL-17 were compared between the two groups.According to the severity of asthma,the patients were further divided into severe asthma subgroup(n=31)and non-severe asthma subgroup(n=60).Spearman correlation analysis was performed to evaluate the association between serum levels of IL-25,IL-33,CCL-2 as well as CCL-17 and the severity of asthma.Multivariate logistic regression analysis was used to identify independent risk factors for severe exacerbation in children with bronchial asthma.The predictive value of serum IL-25,IL-33,CCL-2 and CCL-17 for severe at-tacks of bronchial asthma was analyzed by using the receiver operating characteristic(ROC)curve.Results The levels of FeNO,IgE,IL-25,IL-33,CCL-2 CCL-17 and VE in the asthma group were significantly higher than those in the healthy group,while the levels of FVC,FEV1,PEF and Raw were significantly lower than those in the healthy group(P＜0.05).The levels of FeNO,IgE,IL-25,IL-33,CCL-2,CCL-17 and VE in the severe group were significantly higher than those in the non-severe group,while the levels of FVC,FEV1,PEF and Raw were significantly lower than those in the non-severe group(P＜0.05).The levels of serum IL-25,IL-33,CCL-2 and CCL-17 in children of the asthma group were positively correlated with the severity of asthma(r=0.382,0.416,0.475,0.501,P＜0.05).The levels of serum IL-25,IL-33,CCL-2 and CCL-17 were in-dependent influencing factors for severe asthma.The area under the receiver operating characteristic curve for the combined detection of IL-25,IL-33,CCL-2 and CCL-17 was greater than that obtained from each individual biomarker.Conclusion The combined prediction of serum IL-25,IL-33,CCL-2 and CCL-17 has relatively high value in predicting the development of severe asthma in chil-dren with bronchial asthma.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.

Objective:To evaluate the reliability and validity of the Chinese version of Consultation and Relational Empathy (CARE) Measure in the Mandarin speaking population.Methods:From March to June 2018, patient interviews and expert consultations were conducted to explore problems of CARE in Mandarin context and preliminary revisions were made to the measure, then the final adapted tool was developed. A questionnaire survey on the validity of the measure was conducted from July to August 2018, among 373 patients from three community health service centers in Beijing Chaoyang District, selected by convenience sampling. The questionnaire included general information of participants and the revised CARE measure. The results of the survey were analyzed for the reliability and validity of Chinese version of CARE measure.Results:In the culture adaptation stage, 30 word-changes and 13 phrase-changes were made to improve the cultural adaptation of CARE. A total of 373 valid questionnaires were were collected with a valid recovery rate of 100.0%. The participants had a mean age of (60.8±13.12) years, with females of 68.6% (256/373), junior high school or high school education of 58.7% (219/373), and retirees of 71.3% (266/373). The results showed that there was a significant difference in scores of each item between the high group (top 27%) and the low group (bottom 27%) ( P<0.001). There was a positive correlation between each item and the total score, with a correlation coefficient between 0.817 and 0.868 ( P<0.001). The reliability analysis results show that the Cronbach′s α of the revised CARE was 0.960. In the content validity analysis, among the 10 items, the proportion of patients who considered the item "not applicable" was between 1.1% and 4.8%, and the proportion who considered the item "important" was between 92.8% and 96.2%. In exploratory factor analysis, KMO=0.944 and Bartlett′s sphericity test P<0.001. One common factor with an eigenvalue>1 was extracted, and the cumulative variance explained by which was 73.85%, with the load value of each item of 0.815-0.909. Conclusion:The revised Chinese version of CARE measure shows good reliability and validity and it can be applied in primary care settings for Mandarin speaking population.

Objective:To investigate the prevalence of and risk factors associated with Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and high-risk human papillomavirus (HPV) coinfections among patients with newly diagnosed syphilis at a hospital in Nanjing. Methods:A cross-sectional study was conducted on patients with newly diagnosed syphilis at the STD Clinic, Hospital of Dermatology, Chinese Academy of Medical Sciences in Nanjing, China from May 2023 to April 2024. Urethral, cervical or rectal swabs were collected according to the gender and types of sexual behavior of the patients. Screening tests for CT, NG and HPV infections were then performed by nucleic acid amplification testing. High-risk HPV testing was performed only in female patients. Univariate analysis was carried out to investigate risk factors associated with CT infection. The chi-square test, chi-square test with continuity correction, or Fisher's exact test was chosen based on the sample size and expected values.Results:A total of 111 newly diagnosed syphilis patients with test specimens were collected, including 71 males (64%) and 40 females (36%), and their ages ranged from 16 to 87 years; there were 82 patients with early syphilis and 29 with late latent syphilis; the number of sexual partners in the past 3 months ranged from 0 to 3. Among the 60 male patients with early syphilis, 1 (1.7%) was co-infected with NG, and 12 (20%) with CT; among the 16 men who have sex with men, 7 (43.8%) were co-infected with CT, while 5 (11.4%) of the 44 heterosexual patients were co-infected with CT, showing a significant difference in CT infection rates between the two groups ( χ2 = 5.80, P = 0.016). Among the 22 female patients with early syphilis, 1 (4.5%) was co-infected with NG, and 8 (36.4%) with CT; among the 12 female patients aged < 25 years, 8 (66.7%) were infected with CT, while none of the 7 patients aged 25-44 years or the 3 patients aged ≥ 45 years were infected with CT, showing a significant difference in CT infection rates among the 3 age groups ( P = 0.005) ; among the 16 female patients with 1 sexual partner in the past 3 months, 3 were infected with CT, while 5 were infected with CT in the 6 female patients with 2-3 sexual partners in the past 3 months, with a significant difference in CT infection rates between the two groups ( P = 0.011). Out of the 40 female patients with syphilis, 16 (40%) were co-infected with high-risk HPV; the HPV infection rates did not differ among different age groups (age groups of < 25 years, 25-44 years, ≥ 45 years: 8/14, 2/9, 6/17, respectively; P = 0.265) . Conclusion:The CT infection rate was relatively high in patients with newly diagnosed early syphilis, and a relatively high infection rate of high-risk HPV was observed in female patients with syphilis aged < 25 years.

The Burkholderia cepacia complex (Bcc) comprises a group of genetically related yet phenotypically diverse Gram-negative opportunistic pathogens. These organisms demonstrate significant pathogenicity in immunocompromised populations, particularly cystic fibrosis (CF) and chronic granulomatous disease (CGD) patients, causing severe infections including pneumonia, bacteremia, and urinary tract infections. Notably, Bcc infection in CF patients may progress to acute respiratory failure or the life-threatening "cepacia syndrome". Of particular concern is the widespread nosocomial colonization by Bcc strains coupled with their sophisticated multidrug resistance mechanisms, which contribute substantially to clinical treatment failures. This review systematically examines the epidemiological characteristics, clinical manifestations and resistance mechanisms of Bcc. The review aims to provide evidence-based references for improving accurate diagnosis and enhancing infection control measures against this challenging pathogen.