Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To compare the prognosis and complications of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) patients undergoing radical cystectomy (RC) followed by ileal neobladder.Methods:The clinical data of 103 patients who underwent orthotopic ileal neobladder in Jiangsu Province Hospital from April 2010 to October 2021 were retrospectively analyzed. There were 51 MIBC patients and 52 NMIBC patients. In the MIBC group, there were 49 males and 2 females, aged (58.1 ± 8.9) years, with American Society of Anesthesiologists (ASA) score of 1-2 in 48 cases and 3 in 3 cases. Open radical cystectomy (ORC) was performed in 2 cases, laparoscopic (LRC) in 34 cases and robot-assisted radical cystectomy (RARC) in 15 cases. In the NMIBC group, there were 49 males and 3 females, aged (55.7 ± 9.9) years, ASA score of 1-2 in 51 cases and ASA score of 3 in 1 case. LRC was performed in 41 cases, and RARC in 11 cases. There were no statistically differences between the two groups in above indicators ( P>0.05). The Clavien-Dindo grading system (CCS) was used to assess the complications, defining CCS Ⅰ-Ⅱ as mild complications and CCS Ⅲ-Ⅴ as severe complications. According to their relationship to the neobladder, complications were be classified as neobladder-related and non-neobladder-related complications. The occurrence of complications and the prognosis of neobladder between MIBC and NMIBC were compared. Results:The average operation time of the MIBC group and NMIBC group were (421.2 ± 119.7) min vs. (439.8 ± 106.2) min. The blood loss were 400 (300, 700) ml vs. 400 (300, 625) ml. The frequency of lymph nodes removed were (14.9 ± 8.3) vs. (14.8 ± 8.5). The postoperative defecation time were 5 (4, 6) d vs. 5 (3, 6) d. And the postoperative hospital stay were 20 (15, 28) d vs. 22 (19, 28) d. There were no statistically differences between the two groups in above indicators ( P>0.05). The MIBC group had a significantly lower rate of pelvic lymph node metastasis [17.6% (9/51) vs. 0(0/52), P=0.001] and tumor thrombosis [23.5% (12/51) vs. 5.8% (3/51), P=0.011] than the MIBC group. Moreover, the NMIBC group had a considerably superior 5-year overall survival (OS) (97.6% vs. 70.2%, P=0.035). The proportion of pads needed in the daytime of the MIBC group and NMIBC group were 14.6% (7/46) vs. 6.7% (3/45). The frequency of urination were (2.0 ± 0.7) h vs. (2.4 ± 0.7) h. Furthermore, The proportion of pads needed at night were 47.9% (23/48) vs. 53.3% (24/45). The frequency of nocturnal urination were 3.1±1.5 vs. 2.3 ± 1.7. And the number of pads needed at night were all 1 (0, 1) pad. The daytime and nighttime incontinence rate were 25.0% (12/48) and 62.5% (30/48) respectively in MIBC, compared to 11.1% (5/45) and 62.2% (28/45) respectively in NMIBC. And the proportion of erectile function retention were 15.8% (6/38) vs. 25.0% (10/40). There were no statistically significant differences in the prognosis of neobladder function between the two groups ( P>0.05). Furthermore, the proportions of mild complications in the MIBC group and NMIBC group were [41.2% (21/51) vs. 51.9 (27/52)]. The proportions of severe complications were [21.6% (11/51) vs. 19.2% (27/52)]. The proportions of neobladder-related complications were [27.5% (14/51) vs. 25.0% (13/52)]. And the proportions of non-neobladder-related complications were [39.2% (20/51) vs. 25.0% (13/52)]. There were no statistically significant differences in the complications between the two groups ( P>0.05). Conclusions:There was no statistically significant difference in functional prognosis and complications of neobladder between MIBC group and NMIBC group, and NMIBC had a better oncologic prognosis.

The aim of this study was to refold the OvisAries leukocyte antigen (OLA) class Ⅰ protein with peptides derived from sheeppox virus (SPPV) to identify SPPV T cell epitopes. Two pairs of primers were designed based on the published sequence of a sheep major histocompatibility complex Ⅰ to amplify the heavy chain gene of OLA Ⅰ α-BSP and the light chain gene of OLA Ⅰ-β₂m. Both genes were cloned into a pET-28a(+) expression vector, respectively, and induced with ITPG for protein expression. After purification, the heavy chain and light chain proteins as well as peptides derived from SPPV were refolded at a ratio of 1:1:1 using a gradual dilution method. Molecular exclusion chromatography was used to test whether these peptides bind to the OLA Ⅰ complex. T-cell responses were assessed using freshly isolated PBMCs from immunized sheep through IFN-γ ELISPOT with peptides derived from SPPV protein. The results showed that the cloned heavy chain and light chain expressed sufficiently, with a molecular weight of 36.3 kDa and 16.7 kDa, respectively. The protein separated via a Superdex^TM 200 increase 10/300 GL column was collected and verified by SDS-PAGE after refolding. One SPPV CTL epitope was identified after combined refolding and functional studies based on T-cell epitopes derived from SPPV. An OLA Ⅰ/peptide complex was refolded correctly, which is necessary for the structural characterization. This study may contribute to the development of sheep vaccine based on peptides.
Animals ; Capripoxvirus ; Epitopes, T-Lymphocyte/genetics* ; Peptides/genetics* ; Poxviridae Infections ; Sheep ; Sheep Diseases

Antigenic purity is important for quality control of the foot-and-mouth (FMD) whole virus inactivated vaccine. The recommended method for evaluation the antigenic purity of FMD vaccine is to check the serum conversion to non-structural protein (NSP) 3AB antibody after 2 to 3 times inoculation of animals with inactivated vaccine. In this study, we developed a quantitative ELISA to detect the amount of residual 3AB in vaccine antigen, to provide a reference to evaluate the antigenic purity of FMD vaccine. Monoclonal antibody (Mab) of NSP 3A and HRP-conjugated Mab of NSP 3B were used to establish a sandwich ELISA to quantify the NSP 3AB in vaccine antigen of FMD. Purified NSP 3AB expressed in Escherichia coli was serially diluted and detected to draw the standard curve. The detectable limit was determined to be the lowest concentration of standard where the ratio of its OD value to OD blank well was not less than 2.0. Results: The OD value was linearly corelated with the concentration of 3AB protein within the range between 4.7 and 600 ng/mL. The correlation coefficient R² is greater than 0.99, and the lowest detectable limit is 4.7 ng/mL. The amount of 3AB protein in non-purified inactivated virus antigen was detected between 9.3 and 200 ng/mL depending on the 12 different virus strains, whereas the amount of 3AB in purified virus antigen was below the lowest detectable limit. The amount of 3AB in 9 batches of commercial FMD vaccine antigens was between 9.0 and 74 ng/mL, whereas it was below the detectable limit in other 24 batches of commercial vaccine antigens. Conclusion: the sandwich ELISA established in this study is specific and sensitive to detect the content of 3AB protein in vaccine antigen of FMD, which will be a useful method for evaluation of the antigenic purity and quality control of FMD inactivated vaccine.
Animals ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus ; Viral Nonstructural Proteins/genetics* ; Viral Vaccines

Objective To review the clinical characteristics of prostate mucinous adenocarcinoma cases and update literatures,and recommend the corresponding clinical treatment strategy.Methods From October 2010 to March 2018,36 cases of prostate mucinous adenocarcinoma were involved from 5 urinary centers in China,including 9 cases from Shanghai Changhai Hospital,4 cases from Wuhan Tongji Hospital,13 cases from Shanghai Renji Hospitals,8 cases from the First Affiliated Hospital of Nanjing Medical University,and 2 cases from Sichuan West China Hospitals.The patients' age were (66.8 ±7.2) years (53-83 years) and the median PSA was 22.89 ng/ ml (2.67-1786 ng/ ml).Prostate biopsy confirmed Gleason score 3 + 3 points in 6 cases,3 + 4 points in 9 cases,4 + 3 points in 5 cases,8 points in 11 cases,and 9 to 10 points in 5 cases.According to D'Amico risk stratification,2 patients were in the low-risk group,9 in the intermediate-risk group,and 25 in the high-risk group.Eight cases underwent radical retroperitoneal prostatectomy,13 cases underwent laparoscopic radical prostatectomy,and 12 cases underwent robotic laparoscopic radical prostatectomy.Twenty-three cases underwent pelvic lymphadenectomy,including 12 cases of bilateral obturator lymph node dissection,and 11 cases of bilateral obturator + intraorbital + para-vascular para-aortic lymphadenectomy.Results All 36 operations were completed successfully.Twenty-three cases underwent pelvic lymphadenectomy,including 12 of bilateral obturator lymph node dissection,and 11 of bilateral obturator,intraorbital,and para-aortic lymphadenectomy.Pathological examination showed 9 cases of prostate mucinous adenocarcinoma,26 cases of mucinous adenocarcinoma with acinar adenocarcinoma,and 1 case of mucinous adenocarcinoma with neuroendocrine and immunohistochemical positive of MUC2 (+).Among 33 cases undergoing radical surgery,the pathological stage of ≤T2b in 12 cases (36.3％),T2c in 7 cases (21.2％),T3a in 7 cases (21.2％),T3b in 6 cases (18.2％),and T4 in 1 case (3.0％).Four cases had positive pelvic lymph nodes and 9 cases had positive margin.The median follow-up period was 26 months (6-48 months).The biochemical recurrence occurred in 6 patients one year after surgery,including 3 cases in the intermediaterisk group and 3 cases in the high-risk group.Six cases with postoperative biochemical recurrence and 19 cases with PSA ＞ 0.2 ng/ml after radical or palliative resection underwent adjuvant androgen deprivation therapy(ADT),no postoperative adjuvant radiotherapy or chemotherapy was administered,and 4 cases progressed to castration-resistant prostate cancer.Four cases with CRPC were in the high-risk group and had underwent radical surgery,and the median period progressed to CRPC was 26 months(3-37months)with 2 cases of death.However,there was no significant difference in the rate of biochemical recurrence and the incidence of CRPC in the low-risk group,the intermediate-risk group and the high-risk group.In addition,2 cases had metastases,with pelvic MRI presenting pelvic multiple nodular mass in one case which was consistent with recurrence and metastasis at the 5th month after radical surgery,and pathological examination presenting the mucinous adenocarcinoma being neurosecretory in another case and mestastasis being detected on glans at the 3rd months after radical surgery.The recovery rate of urinary continience at 6 and 12 months after radical surgery was 86.2％ (31/36) and 89.7％ (32/36) respectively.Conclusions Prostate mucinous adenocarcinoma is a variant of acinar adenocarcinoma.This study clarifies prostate mucinous adenocarcinoma of Chinese patients with high Gleason scores,advanced pathological stage,variant in prognosis,and prone to recurrence and metastasis.For treatment strategy,the low-risk and intermediate-risk mucinous adenocarcinoma is recommended undergoing radical surgery,and the prognosis maybe good.High-risk mucinous adenocarcinoma could treated with radical surgery or palliative surgery with adjuvant ADT,and most high-risk patients can benefite,with a small number of poor prognosis.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

Objective To study the X-ray findings and clinical factors of the neonatal necrotizing enterocolitis (NEC)and to im-prove the detection rate of neonatal NEC-especially early lesions.Methods To retrospectively analyzed the plain abdominal radio-graphy images and clinical data of the 21 cases with confirmed neonatal NEC by clinical and surgical diagnosis.Results The X-ray findings of neonatal NEC:stageⅠ:10 cases showed the changes in intestinal motility and the interval thickness between the intestine≤2 mm;stageⅡ:① 4 cases showed the interval thickness between the intestine > 2 mm;② 4 cases showed the pneumatosis of the intestinal wall;③ the pneumatosis of the portal vein were three cases;stage Ⅲ:① 3 cases showed seroperitoneum;② pneumoper-itoneum were three cases.18 cases (85%)were the premature infan;1 6 of 21 cases NEC were the low birth weight;neonatal re-spiratory distress syndrome,infection,pneumonia,sepsis,and mechanical ventilation therapy are important risk factors of NEC. Conclusion X-ray findings has characteristic signs in the neonatal NEC.At the early of NEC,it is very important to make the correct diagnosis need combine X-ray performance with the clinical manifestations and risk factors for,with the necessary dynamic follow-up review in the clinical treatment and prognosis.

Objective To research the status of health literacy among a vocational high school in Guizhou province ,and provide the evidence for health education for the students in this school .Methods Independent design a health literacy questionnaire based on Chinese citizens′health literacy questionnaire in 2008 ,and random sampling 380 students from freshman to senior of this school to investigation in November ,2012 .Results 78 .35% of the students in this school had a basic health knowledge ,39 .57% students had a healthy lifestyle and behaviors ,and 66 .61% students had a sense of the basic literacy skills .The difference was statistically significant among the three items(F=651 .710 ,P<0 .01) .From the overall condition of the health literacy ,the students form high-er household income have higher health quotient ,but with no statistically significant (P>0 .05) ,meanwhile ,there was no difference in health quotient on household registration and gender students .With the increase of school age ,student health literacy level was reduced ,the difference was statistically significant (F=3 .657 ,P<0 .05) .Conclusion The health literacy of lifestyle and behavior of students in this school is poor .Education should be targeted to develop healthy habits .As for the junior and senior students ,the school should enhance the health education intensity to improve the health literacy .

Objective: To investigate the anticancer activity of Luteolin (Lu) and its synergism effect with bacillus calmette-guerin (BCG) on human bladder cancer cell line BIU-87. Methods: Cultured BIU-87 cells were treated with different concentrations of Lu alone or the combination of Lu with BCG. MTT assay was used to measure the cell proliferation inhibition, and IC50 was calculated. Cell cycle and apoptosis were analyzed by lfow cytometry with propidiumiodide (PI) staining and Annexin-V FITC/PI dual parameter markers to clarify the mechanism of inhibiting cell proliferation and inducing apoptosis. Caspase-3 and phosphorylated c-Jun N-terminal kinases (P-JNK) expression were measured to detect the apoptosis signal pathways of Lu in cancer cells. Results: Both Lu and BCG apparently inhibited the cell proliferation and induced the apoptosis dose-dependently, and microscope observation showed morphological changes in the apoptosis. Flow cytometry indicated that Lu arrested the cell cycle at G2 phase (P<0.05). It sensitized BCG-induced cytotoxicity and cell apoptosis, and upregulated expression of caspase-3 and activation of JNK (P<0.05). Conclusion: As an effective anticancer agent, Lu can sensitize the effect of BCG by inducing the cell cycle arrest and apoptosis. hTis synergism effect is achieved by activation of caspase-3 and JNK. Combination of Lu with BCG may be one of the potential treatment for bladder cancer.