Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Based on the five core indicators (the case mix index, the proportion of level-4 surgery, the proportion of technical service income in medical income, the proportion of personnel expenditure in business expenditure, and the proportion of fixed part in personnel salary), the authors discussed the guiding significance of " paying attention to the medical level, strengthening the functional orientation, reflecting the technical value, highlighting people-orientation, and ensuring sustainable development" in the high-quality development of public hospitals. In combination with the current situation of a pilot hospital of high-quality development with the corporate supports of National Health Commission and Province Government, the authors explained the common bottlenecks of public hospitals, such as inaccurate functional positioning, weak innovation ability, poor finance structure, poor salary system and insufficient attention to talents. In the last, the authors pointed out that high-quality development was the development of deepening reform, innovation driven, structural optimization, talent oriented, people-oriented and under the leadership of the Communist Party of China, and put forward targeted implementation paths to provide reference for the pilot work.

Vibrio splendidus is an opportunistic pathogen in aquaculture. It can infect a variety of aquaculture animals and has caused huge losses to the aquaculture industry. In this study, a novel and efficient method for detecting V. splendidus was developed by combining the exonuclease Ⅲ amplification strategy with a nucleic acid test strip developed based on gold nanoparticles-labeled DNA probe. The results could be directly visualized by naked eyes, and this system overcame the difficulty in preparation of the monoclonal antibody used in conventional immunostrip. Upon optimization of experimental conditions, the detection limit of the strip was 5 ng/mL for the synthetic oligonucleotide DNA fragment and 10 ng/mL for the actual genomic DNA sample of V. splendidus. This test strip was more sensitive compared with the PCR method and was specific for the detection of V. splendidus. The rapid preparation of nucleic acid strip and the efficient detection of V. splendidus open a new way for the prevention and control of aquatic diseases.
Animals ; DNA Probes ; Gold ; Metal Nanoparticles ; Vibrio/genetics*

Objective: To examine the expression levels of hypoxia inducible factor (HIF)-1α and α-smooth-muscle actin (SMA) in both cervical cancer tissues with concurrent chemoradiotherapy and non-cervical cancer tissues, and assess the clinical significance in cervical cancer. Methods: The immune-histochemistry was used to detect HIF-1α and α-SMA in 68 cases of cervical cancer tissues and 56 cases of non-cervical cancer tissues (including normal cervical tissues, hysteromyoma and cervical intraepithelial neoplasias) from January 2013 to January 2014 in the First Affiliated Hospital of Hebei Northern University. Results: The positive expression rates of HIF-1α and α-SMA in cervical cancer tissues and non-cervical cancer tissues were 58.8% (40/68), 39.3% (22/56) and 54.4% (37/68), 35.7% (20/56) respectively; the differences were significant statistically (P<0.05). The expression of HIF-1α was positively correlated with the expression of α-SMA protein in cervical cancer tissues (r = 0.376, P =0.001). The positive expression of HIF-1α was closely related to International Federation of Gynecology and Obstetrics (FIGO) stages (r = 0.371, P = 0.004), lymph node metastasis (r = 0.243, P = 0.039), abdominal aortic parathyroid lymph node metastasis (r = 0.286, P = 0.014) and serum squamous cell carcinoma antigen (SCC-Ag) (r = 0.271, P = 0.020), but it was not correlated with age and tumor size (P>0.05). The positive expression of α-SMA was associated with lymph node metastasis (r = 0.363, P = 0.001), abdominal aortic parathyroid lymph node metastasis (r = 0.271, P = 0.020) and SCC-Ag (r = 0.272, P = 0.020), but it was not correlated with age, FIGO stage and tumor size (P>0.05) . The short-term effect rates of concurrent chemoradiotherapy in cervical cancer tissues with positive and negative expression of HIF-1α and α-SMA were 27.5% (11/40), 21.6% (8/37), and 64.3% (18/28) and 48.4% (15/31), and there were statistical differences (P<0.05). The medial follow-up time of 68 cases was 60 months, and the 5-year survival rate was 52.9% (36/68). The 5-year survival rates of the patients with positive expression of HIF-1α and α-SMA were 42.5% (17/40) and 40.5% (15/31), the 5-year survival rates of the patients with negative expression of HIF-1α and α-SMA were 67.9% (19/28) and 67.7% (21/31), and the differences were statistically significant separately (χ² = 4.091 and 4.573, P = 0.043 and 0.032). Conclusions The elevation of HIF-1α and α-SMA may be used to predict the development and prognosis of cervical cancer with concurrent chemoradiotherapy.

Objective: To explore the effects of the clinical nursing experience when diabetes liaison nurses were trained by the experience of Diabetic complications method. Methods: An in- depth interview was conducted on 15 liaison nurses who were undergoing Diabetic complications experience. Data were analyzed by Colaizzi analysis procedure. Results: Totally five themes were refined, namely: updating knowledge, enhancing Mental toughness、Nursing soft skills、Empathy ability and make nursing and patient relationship more harmonious, and have a positive career attitude. Conclusion The experience training of complications can reduce the psychological pressure of diabetes nurses, improve the soft skills, mental toughness and the ability of transposition thinking, and explore a new way for the training of nurses. Further optimize the training time, content and models, so as to better improve the quality of nursing service and improve the comprehensive ability of nurses.

Objective To investigate the chang and impaction of TM and D- Dimer on peripherally inserted central catheter (PICC) associated thrombosis in cancer patients. Methods The expression of TM and D-Dimer from 207 cancer patients with PICC was examined using nzyme-linked immunoassay. Paitents were divided into thrombosis group and control group according to Doppler Sonography. Results The thrombosis group had 33 cases and the control group had 174 cases in 207 malignant tumor patients with PICC. Compared with that in control group, the expression of TM (6.806 ± 1.805)μg/L and D-Dimer (0.786 ± 0.294) mg/L was significantly higher in thrombosis group and respectively statistically significant (P<0.05), The expression of TM and D-Dimer was positively correlated with thrombosis respectively (r=0.572 and 0.530, P<0.05). The multi-factor Logistics analysis showed the odd ratio of TM was 1.899 and the odd ratio of D-Dimer was 7.292, and the difference was statistically significant (P<0.05). Patients were dichotomized into elevated and noneelevated groups according to the 50th percentile of the levels of TM and D-Dimer of the total study population. In multivariable analysis, the odd ratio of both elevated TM and elevated D-Dimer was 2.04, which was higher than elevated TM (1.286) alone and elevated D-Dimer (1.044) alone, and there was difference in statistics (P<0.05). The results showed that the risk of PICC associated with thrombosis in both elevated TM and elevated D-Dimer TM increased 2.042 times. The expression of TM and D-Dimer was correlated with clinical stage respectively (r=0.477 and 0.492, P<0.05);but was not correlated with age, sex, site of tumor and concurrent radiochemotherapy (P>0.05). Conclusions The expression of TM, D-Dimer is elevated, which is expected to assess the early diagnosis and clinical value of PICC associated thrombosis in cancer.

The protein production system using a baculovirus Antheraea pernyi nucleopolyhedrovirus (AnpeNPV) as a gene expression vector and its host insect as a natural bioreactor was successful established and its excellent performance in the protein production has been demonstrated. In this paper, the system is used to produce recombinant human epidermal growth factor (rhEGF), which have been widely used in medical and cosmetic treatment. A recombinant AnpehEGF virus has been constructed by replacing the viral polyhedrin gene with the rhEGF gene, and then injected it to Samia cynthia ricini pupae. Amplification and expression of rhEGF gene in the pupae was clearly detected by PCR, Western blot and ELISA analyses. These analyses have also revealed that rhEGF in the pupae was significantly increased at 6 days post-infection, and reached maximum level at the 12th day. The concentrations of rhEGF were 19.77, 24.90, 618.59 and 1 952.46 ng/g pupae at 3, 6, 9 and 12 days post-infection, respectively. However, the rhEGF concentration reduced at later stage (days 15). The rhEGF in the pupae could be purified using ammonium sulfate precipitation and Ni-NTA agrose affinity chromatography. Results demonstrate that Samia cynthia ricini pupae can be used as a bioreactor to produce rhEGF and, if successfully improved, will be a novel method of rhEGF production with lower cost and more efficient.
Amino Acid Sequence ; Animals ; Bombyx ; genetics ; metabolism ; Epidermal Growth Factor ; biosynthesis ; genetics ; Genetic Vectors ; genetics ; Humans ; Molecular Sequence Data ; Nucleopolyhedrovirus ; genetics ; Recombinant Proteins ; biosynthesis ; genetics