Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

Objective:To investigate the effect of low-dose ionizing radiation on blood cell parameters of radiation workers.Methods:A total of 124 staff members engaged in radiology were selected into the observation group, and they were divided into 4 subgroups of physicians, physicists, technicians, and maintainer according to their jobs. A total of 130 non-radiation-related staff members from the same hospital were selected into the control group. Blood cell parameters of peripheral blood of all subjects from 2016 to 2019 were collected, and the differences in blood cell parameters between the radiation group and the control group as well as 4 subgroups of the control group were analyzed and compared, and the correlation between the differences in blood cell parameters and the cumulative radiation dose was compared.Results:Compared with the control group, the white blood cell count, neutrophil count, red blood cell count and hemoglobin count in the observation group were lower than those in the control group (all P<0.05). There are no significant differences in cumulative radiation dose among different types of work (all P>0.05). Correlation analysis showed that the blood cell parameters of peripheral blood cells were not significantly correlated with the cumulative radiation dose. The blood cell count changes after 4-year low-dose ionizing radiation between the physicist group, the technician group and the maintainer sub-group were significantly different (all P<0.05), but the above differences were not related to the cumulative radiation dose (all P>0.05). Conclusions:Under the same exposure and protection conditions, the blood cell counts of different radiation-related workers are not significantly different, and the long-term cumulative radiation dose has no significant correlation with blood cell parameters. Therefore, peripheral blood cell parameters can no longer be used as a good indicator to reflect radiation damage, and it is urgent to find more convenient, intuitive and sensitive indicators of radiation damage.

Objective:To compare the dosimetry and efficacy of intracavitary brachytherapy (ICBT) and intracavitary/interstitial brachytherapy (IC+ ISBT) based on CT image guidance in the treatment of stage Ⅲ B cervical cancer. Methods:Clinical data of 93 patients with stage Ⅲ B cervical cancer treated in Department of Radiotherapy of Jilin Cancer Hospital from June 2014 to February 2017 were analyzed retrospectively. According to the results of Gynecological examination and pelvic MRI before brachytherapy, confirming the size of residual tumor and the degree of parauterine infiltration, all patients were divided into the ICBT and IC+ ISBT groups. The D 90%, D 100%, V 100% and D 2cm 3 of bladder and rectum were compared, and the short-term and long-term efficacy was observed between two groups. Results:The median follow-up time was 60 months. The 5-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 83%, 71% and 68%, respectively. Compared with the ICBT group, HR-CTV D 90% in the IC+ ISBT group was all more than 85 Gy, while there was no significant difference between two groups ( P=0.188). The D 2cm 3 of bladder and rectum in the IC+ ISBT group was significantly decreased by 7 Gy and 8 Gy (both P<0.01), and the distant metastasis-free survival rate was significantly improved ( P=0.009). The 5-year local control rate in the HR-CTV volume>60 cm 3 in the IC+ ISBT group was significantly higher than that in the IC group ( P=0.029). Conclusion:For patients with Ⅲ B cervical cancer, IC+ ISBT can not only ensure target coverage, but also significantly reduce the incidence of distant metastasis and the dose of organs at risk, and significantly improve the local control rate of large tumors.

Objective:To establish a patient-derived xenotransplantation (PDX) animal model of gastric cancer, and observe the anti-cancer effect of chemotherapeutic drugs on this model.Methods:Human gastric cancer tissues were inoculated into the subcutaneous tissues of both axillaries of NOG mice and were subcultured for 3 generations. The tumor tissues of the third-generation NOG mice were selected and inoculated into the subcutaneous tissues of left axillary of 21 severe combined immunodeficiency-non-obese diabetes mellitus (SCID-NOD) mice to establish PDX mouse model of gastric cancer. The inoculated mice were divided into control group (mice received only 0.9% sodium chloride injection), oxaliplatin group, cisplatin group, paclitaxel group, fluorouracil group, tegafur, gimeracil and oteracil porassium capsules group and capecitabine group, with 3 mice in each group, and the corresponding drugs were given. The mice survival status, tumor volume and tumor weight at different times were recorded. Mice were sacrificed on the 61st day of administration, and the tumor inhibition effects of 6 kinds of chemotherapy drugs on the PDX model of gastric cancer were evaluated.Results:After being subcultured for 3 generations, the stability of tumor transmission in PDX animal model of gastric cancer was improved, and the homogeneity of tumor growth was good at the initial stage. At the early stage of administration, the model was more sensitive to oxaliplatin, fluorouracil and capecitabine, and the tumor growth inhibition (TGI) values on the 31st day were 63.37%, 52.11% and 78.48%, at the end of administration, the model had the best sensitivity to capecitabine with a TGI value of 59.22% and a tumor inhibition rate of 58.65% on the 61st day. The TGI curve after administration showed that paclitaxel had no obvious anti-tumor effect, cisplatin had the worst anti-tumor effect, and the model had poor tolerance to tegafur, gimeracil and oteracil porassium capsules.Conclusion:The PDX animal model of gastric cancer is successfully established, and capecitabine has the best tumor suppressive effect on this model.

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

Objective To establish a method for preparing orthotropic transplantable hepatocellular carcinoma in mice. Methods According to the liver detailed anatomical structure of the mouse, 50 μl mouse ascites containing 1 ×106 and 5 ×105 mouse hematoma H22 cells was input to liver in 12 Kunming mice through percutaneous intraperitoneal injection by syringe, respectively, to establish orthotopic transplantable hepatocellular carcinoma model. The growth status of mice was observed, and the pathological changes of liver and tumor metastasis tissues were detected. The tumor formation and metastasis were analyzed. Results The tumor formation rate was 100% (12/12) by direct injection of mouse hematoma H22 cells in 2 groups. The inoculated mice started to appear ascites at the 6th day, and all mice produced ascites at the 10th day. The survival time was (16.17 ±3.07) d and (18.08 ±3.34) d in 1 ×106 group and 5 ×105 group, respectively. Some mice emerged tumor metastasis in kidney, intestine, spleen and mesenteric lymph nodes. Conclusion The method of direct injection could establish orthotropic transplantable hepatocellular carcinoma model in mice, which can be used for antitumor drug research.

Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity (>0.995) within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80-120%. The excretion recoveries of Rg1, ginsenoside Rh1 (Rh1), and protopanaxatriol (Ppt) in bile, urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were 40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile. Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.

OBJECTIVETo investigate whether inhalable particulate matters can cause the damage of chromosome or mitotic apparatus to produce micronucleus, and to evaluate genetic toxicology of moxa smoke on chromosome.

METHODSBy MTT method, the 24 h half maximal inhibitory concentration (IC50) of moxa smoke condensation (MSC) on Chinese hamster ovary (CHO) cells was 0.087 mg/mL. CHO cells, which were cultured in vitro, were divided into a solvent control group, a positive control group (cyclophosphamide as solvent), a low concentration group, a moderate concentration group and a high concentration group. The low concentration group, moderate concentration group and high concentration group were set approximately 1/8, 1/4, 1/2 of IC50, respectively. Whether micronucleus had dose-effect response induced by the damage of chromosome or mitotic apparatus was observed after CHO cells were contaminated by MSC in the low concentration group, moderate concentration group and high concentration group.

RESULTSThe rate of micronucleus induced by MSC in the low concentration group, moderate concentration group and high concentration group was higher than that in the solvent control group (all P < 0.05), which presented dosage-effect response. The experiment was repeated 3 times, indicating it was repeatable with statistical significance.

CONCLUSIONHigh concentration of MSC shows toxicity to induce chromosome damage, which disappears at low concentration. The genetic toxicology is also dependent on concentration, and the concentration of moxa smoke is essential. In clinical treatment, it is noted to control the level of moxa smoke, while the clinical safety standard of moxa smoke concentration is in need of further study.

Air Pollutants ; adverse effects ; Animals ; CHO Cells ; Cell Nucleus ; drug effects ; genetics ; Cricetinae ; Cricetulus ; Inhalation Exposure ; adverse effects ; analysis ; Micronucleus Tests ; Moxibustion ; adverse effects ; Particulate Matter ; adverse effects ; Smoke ; adverse effects ; analysis

Objective To investigate the effects of ozone (O3) on Wnt/β-catenin signaling pathway in the articular cartilage of rats with osteoarthritis (OA).Methods Eighteen male SPF Wistar rats,aged 3 months,weighing 200-250 g,were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),group OA,and O3 group (group O).OA was induced by injection of monosodium iodoacetate 3 mg (50 μl) into the right knee joint cavity.On 7th day after the model was established successfully,25 μg/ml O3 1 ml were injected into the knee joint cavity,once a week for 3 consecutive weeks in group O.Behavioral changes were observed after establishment of the model.At 1 day before establishment of the model,and 1,4,7,14,21 and 28 days after establishment of the model,the mechanical paw withdrawal threshold (MWT) was measured.At 28 days after establishment of the model,the total knee joint was removed and stained with haematoxylin and eosin for examination of the pathological changes of the cartilage (under light microscope) and for determination of the expression of β-catenin and matrix metalloproteinase-13 (MMP-13) in the cartilage (by immunohistochemistry).Results The signs of OA such as hind-limb motor dysfunction,knee joint swelling,or decreased joint motion,and signs of hyperalgesia such as lickings were observed after establishment of the model in rats.Compared with group C,the MWT was significantly decreased at each time point after establishment of the model,and the ex pression of β-catenin and MMP-13 in the cartilage was significantly up-regulated in the other two groups(P＜0.05).Compared with group OA,the MWT was significantly increased at 7-28 days after establishment of the model,and the expression of β-catenin and MMP-13 in the cartilage was significantly down-regulated in group O (P＜0.05).The pathological changes of the cartilage were significantly reduced in group O as compared with group OA.Conclusion The mechanism by which O3 mitigates OA is probably related to inhibition of Wnt/β-catenin signaling pathway activation in the articular cartilage in rats.

OBJECTIVETo observe the effects of intervention of moxa smoke with different concentrations on superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and lung of male rats, so as to explore the safety concentration of moxa smoke.

METHODSA total of 32 Wistar male rats were randomly divided into a control group, a low-concentration group, a moderate-concentration group and a high-concentration group, 8 rats in each one. All the rats were exposed in the full-automatic toxicant exposure cabinet, and the overshadow of moxa smoke was set at 0%, 10%, 40% and 70%, respectively. Each rat was exposed for 20 min per day. After 26 weeks, the activities of SOD and content of MDA in serum, lung organ and bronchoalveolar lavage fluid were tested.

RESULTSCompared with the control group, the activities of serum SOD in the high-concentration group were reduced (P< 0. 05), but those in the low-concentration group and moderate-concentration group were not significantly different (both P>0. 05). Compared with the control group, the content of serum MDA in the low-concentration group, moderate-concentration group and high-concentration group was increased insignificantly (all P>0. 05). There were no significant differences regarding activities of SOD and content of MDA in lung organ and bronchoalveolar lavage fluid among each moxa smoke group (all P>0. 05).

CONCLUSIONThere is no obvious toxic reaction in the low-concentration group and moderate-concentration group; in the high-concentration group the antioxidant ability is damaged due to long-term exposure.

Animals ; Artemisia ; chemistry ; Lung ; enzymology ; metabolism ; Male ; Malondialdehyde ; blood ; metabolism ; Moxibustion ; Rats ; Rats, Wistar ; Smoke ; analysis ; Superoxide Dismutase ; blood ; metabolism