Bacterial therapy has attracted increasing attention due to its special mechanism and abundant applications. With the flourishing development of synthetic biology, therapeutic genes have been introduced into engineering bacteria to improve their antitumor efficacy. However, it is difficult to spatiotemporally control the expression of these therapeutic genes at the tumor site in vivo, thereby considerably limiting the application of engineered bacteria in tumor treatment. To resolve this problem, we constructed a temperature-responsive bacterial strain capable of triggering the expression of exogenous genes in a laser-controllable way. Noxa, a pro-apoptotic protein, is chosen to test the expression of exogenous protein and its anti-tumor effect in engineered bacteria upon laser irradiation. Firstly, Noxa was fused to the C-terminus of the bacterial outer membrane protein cytolysin A (ClyA), and then the recombinant gene fragment ClyA-Noxa was inserted into the temperature-sensitive plasmid pBV220 and the recombinant plasmid was transformed into non-pathogenic Escherichia coli MG1655. Thus, we constructed the engineering strain (TRB@Noxa) that could express Noxa on the bacterial surface. TRB@Noxa could target and colonize the tumor tissue without causing notable host toxicity. The bacterial infection triggered thrombosis in the tumor tissue, resulting in the darkness of tumor sites. In a xenograft mouse tumor model, our strategy demonstrated precise tumor targeting and strong tumor inhibition. In conclusion, we successfully constructed a new engineering bacterial strain TRB@Noxa. TRB@Noxa combined with photothermal therapy could arrest tumor growth in the absence of photosensitizers, which represents an appealing method for antitumor therapy in the future.
Escherichia coli/radiation effects* ; Animals ; Humans ; Lasers ; Mice ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Neoplasms/therapy* ; Genetic Engineering ; Cell Line, Tumor ; Escherichia coli Proteins/genetics*

Heart rate recovery,a widely used indicator in clinical evaluation of the autonomic nervous system,refers to the difference between maximum heart rate during exercise and the heart rate after 1 or a few minutes of cessation.It possesses advantages of being noninvasive and repeatable.Currently,heart rate recovery is extensively applied in cardiovascular diseases for evaluating disease severity,prognosis,risk of cardiovascular events,and mortality.This article primarily discusses the application value and current research progress of heart rate recovery in cardiovascular diseases.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Objective:To systematically evaluate the intervention effect of exposure and response prevention (ERP) on obsessive compulsive disorder (OCD).Methods:PubMed, Web of Science Core Collection, EBSCO, Cochrane Library, Embase, Science Direct, Wanfang Data, China National Knowledge Infrastructure and VIP-CSTJ were used to collect randomized controlled studies related to ERP for OCD.Randomized controlled studies that met the criteria were included, with the score of Yale-Brown obsessive-compulsive scale as the primary outcome indicator and the scores of anxiety and depression scale as secondary outcome indicators, while the included literatures were evaluated for literature quality and data extraction.Review Manager 5.3 and Stata 16.0 softwares were used to conduct Meta-analysis on the extracted data.Results:Twenty-seven studies with a total of 1 239 patients were included, and 599 cases in the ERP group and 640 cases in the control group.Meta-analysis results showed that the efficacy of ERP group was significantly better than that of blank control group(MD=-6.55, 95% CI: -8.75--4.35, P<0.001) and significantly better than chlorpromazine control group treatment (MD=-5.88, 95% CI: -8.20--3.56, P<0.001) for improving patients' obsessive-compulsive symptoms, but not significantly different from CBT intervention (MD=0.21, 95% CI: -1.62-2.04, P=0.82), and the efficacy of ERP and CBT had no significant during the post-intervention follow-up period (MD=0.41, 95% CI: -2.45-3.27, P=0.78). For improving patients' depressed mood, ERP was effective in improving patients' depressed mood (SMD=-0.45, 95% CI: -0.74--0.17, P=0.002), but not significantly different from CBT (SMD=-0.05, 95% CI: -0.27-0.16, P=0.62). For improving anxiety, the efficacy of ERP group was not different from that of control group (SMD=-0.17, 95% CI: -0.56-0.23, P=0.41). Conclusion:ERP has good feasibility in improving obsessive-compulsive symptoms and depression in patients with OCD.However, long-term efficacy was not verified for improving anxiety and maintaining long-term efficacy during the follow-up period.

Chalcone is a common scaffold in natural products with optimal properties and biological activities.In this study, we designed and prepared eight new coumarin-chalcone derivatives (5a-5h), and confirmed their structures by 1H NMR and 13C NMR. Their in vitro antifungal activity combined with fluconazole (FLC) against drug-resistant Candida albicans was tested by microdilution method.The results indicated that most chalcone derivatives showed good antifungal activity against drug resistant Candida albicans with FLC, particularly with compound 5g displaying better antifungal activity (MIC50 = 5.60 μg/mL) than FLC (MIC50 = 200 μg/mL) when combined with FLC, so, these derivatives could be used as synergists of antifungal drugs.

Objective:To compare the efficacy of concurrent and asynchronous radiochemotheray for early extranodal nasal natural killer/T-cell lymphoma (NKTCL).Methods:From 2007 to 2020, 278 patients with early NKTCL treated with comprehensive treatment in the Affiliated Tumor Hospital of Guizhou Medical University were recruited. According to the adjusted Nomogram-revised risk index (NRI) prognostic model, there were 49 cases in the good prognostic group without adverse prognostic factors (age>60 years old, increased serum lactate dehydrogenase (LDH), ECOG score ≥2, primary tumor invasion (PTI), Ann Arbor stage Ⅱ, and 229 cases in the poor prognostic group with any adverse prognostic factors. 145 of these cases were treated with concurrent radiochemotherapy, and 133 of them were treated with asynchronous radiochemotherapy.Results:The 5-year overall survival (OS) rate of the whole group was 71.0%, and the progression-free survival (PFS) rate was 67.6%. The 5-year OS rate in the good prognostic group was 95.6%, and 65.4% in the poor prognostic group ( P<0.001). In the poor prognostic group, the 5-year OS rates of patients with NRI=1(low-and moderate-risk group), NRI=2(moderate-and high-risk group), NRI≥3(high-risk group) were 72.1%, 61.1% and 47.7%, respectively ( P=0.007). There was no significant difference in curative effect between the concurrent and asynchronous radiochemotherapy groups. The 5-year OS rates were 70.6% and 69.8%( P=0.783), and the 5-year PFS rates were 67.6% and 65.2%( P=0.631). Further stratified analysis showed that the 5-year OS rates of patients with NRI=1 receiving concurrent and asynchronous radiochemotherapy were 73.1% and 76.5%( P=0.576), 62.6% and 69.3%( P=0.427) for those with NRI=2, and 58.1% and 42.3% for those with NRI≥3( P=0.954). Conclusions:Comprehensive treatment can significantly improve the prognosis of early NKTCL in the poor prognostic group. In the sequence of radiotherapy and chemotherapy, there is no significant difference in 5-year OS and PFS rates between concurrent and asynchronous radiochemotherapy. Sequential treatment with better tolerance can be adopted for early NKTCL with poor prognosis.

Organic chemistry is an important foundation course for medicine, chemistry and other majors in universities and colleges. In this study, combined with the characteristics of pharmacy students in local colleges and universities, teachers introduced case teaching, enhanced curriculum connotation, and explored the integration of green chemistry concepts into the teaching process of organic chemistry, so as to cultivate pharmaceutical professionals with environmental protection concept and safety awareness. The practice shows that this teaching model not only improves students' attention to organic chemistry and learning efficiency, but also improves students' comprehensive quality.

Objective:To analyze the efficacy and prognostic factors of radiotherapy combined with asparaginase/peaspartase-based chemotherapy regimen in the treatment of early stage extranodal natural-killer/T cell lymphoma of the upper aerodigestive tract (UADT ENKTCL).Methods:267 early stage UADT ENKTCL patients were treated in Guizhou Cancer Hospital from October 2003 to February 2020. Among them, 229 patients received radiotherapy or radiotherapy combined with menpartaminase/permenidase-based chemotherapy regimen and 38 patients were treated with radiotherapy or chemotherapy alone. The overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan- Meier method, log-rank test was conducted for univariate analysis and Cox regression model was performed for multivariate analysis. Results:The 5-year OS and PFS were 67.2% and 61.5% in all patients. The 5-year OS and PFS in patients treated with radiotherapy combined with chemotherapy, radiotherapy alone and chemotherapy alone were 71.7%, 35% and 49%(all P<0.001), and 66.4%, 35% and 28%(all P<0.001), respectively. According to the NRI risk stratification, 246 patients treated with radiotherapy and chemotherapy were divided into the favourable and the unfavourable prognosis groups. The 5-year OS was 93.3% and 64.3%( P<0.001) and the 5-year PFS was 91.1% and 56.7%( P<0.001) in two groups. For patients receiving radiotherapy with a dose ≥50 Gy and<50 Gy, the 5-year OS was 72.4% and 55.7%( P<0.001), and the 5-year PFS was 68.3%, and 36.5%( P<0.001). In the unfavourable prognosis group, the 5-year OS of patients receiving ≥ 4 and<4 cycles of chemotherapy was 65.5% and 59.2%( P=0.049), and the 5-year PFS was 60.7% and 50.6%( P=0.018). Univariate analysis showed that stage Ⅱ, ECOG≥2, primary tumor invasion, radiotherapy alone, NRI≥1(Nomogram-revised risk index), EBV-DNA≥2 750 copies/ml, radiotherapy dose < 50 Gy, and<4 cycles of chemotherapy were associated with unfavorable 5-year OS and PFS (all P<0.05), and CHOP-like regimen was the risk factor of unfavorable 5-year PFS ( P<0.05). Multivariate analysis demonstrated that primary tumor invasion, ECOG≥2, and radiotherapy dose <50 Gy were associated with unfavorable OS and PFS (all P<0.05), and stage Ⅱ was the risk factor of unfavorable 5-year OS ( P<0.05). Conclusions:The prognosis of early stage low-risk UADT ENKTCL of is favourable. Sufficient dose of extended involved-field radiotherapy is an important curative modality in early stage UADT ENKTCL. Compared with radiotherapy alone, radiotherapy combined with chemotherapy can significantly improve the prognosis of early stage UADT ENKTCL patients in the unfavourable prognosis group. Full-course chemotherapy can significantly prolong the long-term survival in the unfavorable prognosis group. The chemotherapy containing asparaginase can significantly enhance the prognosis of patients with early stage UADT ENKTCL.

Objective:To analyze the efficacy and prognostic factors of induced chemotherapy combined with radiotherapy in the treatment of early stage extranodal natural-killer/T cell lymphoma (ENKTCL).Methods:Two hundred and eighty-seven early stage NKTCL patients were treated in Affiliated Cancer Hospital of Guizhou Medical University from October 2003 to October 2021. All patients were aD ministrated with short courses of induced chemotherapy combined with radiotherapy. Clinical prognostic factors of early stage NKTCL were analyzed. The overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan- Meier method, log-rank test was conducted for univariate analysis and Cox models were performed for multivariate analysis. Results:The 5-year OS and PFS were 72.8% and 68.9% in all patients. According to Nomogram risk index (NRI) prognostic model, 286 patients were divided into the low risk (NRI=0), intermediate low risk (NRI=1), intermediate high risk (NRI=2), high risk (NRI=3) and very high risk (NRI≥4) groups. In these 5 groups, the 5-year OS were 95.6%, 76.3%, 69.5%, 61.0% and 23.3%(all P<0.001), and the 5-year PFS were 93, 2%, 69.8%, 64.6%, 60.2% and 23.3%(all P<0.001), respectively. In the radiotherapy with a dose of ≥50 Gy and<50 Gy groups, the 5-year OS were 73.8% and 65.9%( P=0.123) and the 5-year PFS were 72.8% and 45.3%( P=0.001). According to the response to induced chemotherapy of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD), the 5-year OS were 85.4%, 74.0%, 61.8% and 28.5%(all P<0.001), and the 5-year PFS were 83.7%, 66.8%, 65.7% and 27.4%(all P<0.001), respectively. Univariate analyses showed that stage Ⅱ, ECOG≥2, primary tumor invasion, radiotherapy dose<50 Gy and short-term efficacy of induced chemotherapy were poor prognostic factors for the 5-year OS and PFS (all P<0.05). Multivariate analyses demonstrated that primary tumor invasion, ECOG≥2 and stage Ⅱ were poor prognostic factors for OS (all P<0.05), and primary tumor invasion and ECOG≥2 were poor prognostic factors for PFS (all P<0.05). Conclusions:Early stage NKTCL patients can obtain high efficacy after induced chemotherapy combined with radiotherapy. Complete response to induced chemotherapy is associated with favorable prognosis.

Objective:To evaluate the therapeutic efficacy and side effects of P-Gemox regimen combined with intensity modulated radiotherapy in the treatment of extranodal NK/T cell lymphoma, nasal type (ENKTL).Methods:The data of 60 patients with ENKTL confirmed by pathomorphology and immunohistochemistry in Guizhou Cancer Hospital from July 2014 to October 2019 were retrospectively analyzed. All patients received P-Gemox chemotherapy combined with intensity modulated radiotherapy (at least 2 cycles), and the efficacy and adverse reactions were evaluated.Results:The complete remission rate of 60 patients was 65.0% (39/60), the partial remission rate was 25.0% (15/60), and the total effective rate was 90.0% (54/60). The main side reactions were myelosuppression, transaminase elevation and radiation mucositis; most of them were mild to moderate, which were relieved after treatment or the withdrawal of radiotherapy and chemotherapy. No treatment-related death cases were found. The overall survival rate of 1-year, 2-year, 3-year was 91%, 75% and 69%; the progression-free survival rate of 1-year, 2-year, 3-year was 86%, 68% and 62%. During the treatment, 3 cases died due to the progress of the disease and infection. Multivariate analysis showed that with and without hemophagocytic syndrome and radiotherapy dose were related to prognosis (all P < 0.05). Conclusion:P-Gemox, as the first-line induction chemotherapy regimen combined with intensity modulated radiotherapy has good short-term efficacy and safety for patients with ENKTL.