Objective To prepare a red blood cells based multifunctional nanoscaled drug delivery system,and to study its in vitro photothermal and photodynamic effects.Methods The indocyanine green (ICG)/doxorubicin (DOX) co-loaded nanoscaled red blood cells (DIRAs) were prepared using an extrusion method.The morphology,particle size,encapsulation efficiency,and stability were determined.The heating related change of particle size was studied using a size and potential tester.The in vitro photothermal effect was studied using an infrared imaging device.The uptake of DIRAs to 4T1 cells was studied using a CLSM examination.The in vitro photodynamic effect was studied using a fluorescence probe and CLSM examination.Results DIRAs were successfully prepared with a uniform and homogeneous size which was about (97.0±20.1) nm.The Zeta potential was about-21.6 mV and the encapsulation efficiency of ICG and DOX were 93.5％ and 95.2％,respectively.The DIRAs had excellent stability within 28 days.This nanoscaled drug delivery system had identical photothermal effect compared to free ICG.The cellular uptake of DOX was significantly improved after the laser irradiation and the photodynamic effect was enhanced.Conclusions The prepared DIRAs have regular shape,suitable particle size,high encapsulation efficiency and high photothermal conversion efficiency.DIRAs can improve the cellular uptake of DOX and enhance the photodynamic efficiency.This biomimetic muhifunctional nano-system could facilitate breast cancer treatment by combining PTT7PDT and chemotherapy.

Objective:To construct an evaluation index system for the elderly stressors, so as to provide a basis for comprehensive and effective stressor assessments for the elderly.Methods:With the bio-psycho-social medicine model as the theoretical guide, the first draft of the evaluation index system for the elderly stressors was drawn up through the literature analysis and the semi-structured interview. The Delphi method was used to conduct two rounds of expert consultations to 13 experts. The analytic hierarchy process was used to determine all levels of indicators and their weights.Results:In two rounds of expert consultations, the expert positive coefficients were 86.67% and 100.00% respectively, and the authority coefficients were both 0.889, and the Kendall coordination coefficients were 0.339 and 0.361 respectively ( P<0.05) . The evaluation index system for the elderly stressors included 4 first-level indicators, 12 second-level indicators and 65 third-level indicators. Conclusions:The evaluation index system for the elderly stressors based on the Delphi method is scientific and practical, and can provide a unified standard for the evaluation of the elderly stressors.

Objective To predict the potential suitable distribution areas of Sophora japonica cv.jinhuai in China;To provide a references for resource development and expanded cultivation of Sophora japonica cv.jinhuai.Methods Totally 85 pieces of information on the distribution of sample sites were collected and combined data on 72 environmental factors,and the dominant environmental factors affecting the suitability distribution of Sophora japonica cv.jinhuai were analyzed using the maximum entropy(MaxEnt)model and geographic information system software ArcGIS.Results The five dominant environmental factors influencing the suitability distribution of Sophora japonica cv.jinhuai were dry month precipitation,May light radiation,November precipitation,September mean temperature,and October light radiation.The potentially suitable distribution area of Sophora japonica cv.jinhuai in China was mainly concentrated in the transition zone between south-central Hunan Province and northeast Guangxi Zhuang Autonomous Region.Conclusion The results of this study can provide references for the selection of the cultivation areas of Sophora japonica cv.jinhuai and protection of wild reso of Sophora japonica cv.jinhuai.

Objective To explore the effects of thunder-fire moxibustion in improving affected upper limb hypermyotonia of patients after stroke, so as to provide a clinical basis for improving affected upper limb hypermyotonia (spasm) after stroke. Methods From June 2016 to February 2017, we selected 100 stroke patients from Fastern Area of Dongzhimen Hospital, Beijing University of Chinese Medicine. All of the patients were divided into control group and experimental group according to the order of admission, 50 cases in each group. Patients of control group accepted routine rehabilitation training. On that basis, patients of experimental group were also treated with thunder-fire moxibustion. We compared the rehabilitation efficacy of two groups with the activity of daily living (Barthel) and the Modified Ashworth Scale (MAS). Results The scores of MAS of experimental group were (1.83±0.64) and (1.27±0.85) respectively 14 and 28 days after intervention, lower than those of control group [(2.60±0.79), (1.99±0.85)]with significant differences (t=-2.711, -2.808; P<0.01). There was a significant difference in the score of activity of daily living between experimental group (55.44±19.77) and control group (48.85±13.73), (t=2.112, P=0.037). Conclusions The thunder-fire moxibustion combined with rehabilitation could improve the activity of daily living of patients after stroke and reduce the degree of affected upper limb spasm of patients.

Objective To establish a Real-time quantitative PCR method (qPCR) for the detection of diatom UPA barcoding genes and evaluate its application in the drowning diagnosis. Methods The homologous sequences of diatoms UPA gene was obtained by Blast from GeneBank, based on which the universal primers for diatoms were designed. DNA were extracted from 2 common human symbiotic bacteria (Escherichia coli, Bifidobacterium longum), 3 species of planktonic bacteria, 15 species of planktonic algae, tissue samples (lung, liver and kidney) from human cadavers (28 drowning victims, 1 victims by non-drowning in the water, 3 victims deaths on land) in 32 cases. The specificity, sensitivity and repeatability of the designed primers were tested. The positive rates of diatoms detection in the drowning cases were calculated. The results of the real-time quantitative method were evaluated comparatively by Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy (MD-VF-Auto SEM) and PCR-Capillary Electrophoresis (PCR-CE). Results The results showed that the primers UPA99 had strong specificity for the diatomaceae (Synedra radians, Navicula sp., Melosira varians, Cyclotella sp. and Nitzschia sp.) DNA. The melting curve of the amplified product was smooth; the peak was narrow; the melting temperature was (87±1)℃. The sensitivity of qPCR method was 1.56×10-5ng/μL with the detection range of 1.56×102ng/mL~1.56×10-5ng/μL, in contrast with the PCR-CE method (1.56×10-3ng/μL). This real-time PCR method showed high repeatability and stability with the coefficient of variation less than 2%. The detection rate of lung, liver and kidney was 89.3%, 71.4% and 64.3% respectively. Conclusion The established qPCR method, based on the universal primers designed for diatom UPA gene, has high specificity, high sensitivity and good repeatability. With a promising prospect for application, qPCR is suitable for drowning diagnosis.

Objective:To analyze the difference and clinical significance of reflux related parameters between patients with reflux asthma (RA) and typical gastroesophageal reflux disease (TGERD).Methods:From June 2017 to June 2020, at PLA Rocket Force Characteristic Medical Center, the clinical data of 120 patients with gastroesophageal reflux disease (GERD) who underwent gastroscopy, high-resolution esophageal manometry (HREM) and 24 h pH-impedance monitoring contemporaneously were retrospectively analyzed. The GERD patients were divided into RA group and TGERD group according to the symptom correlated indexes, 60 cases in each group. The reflux related indexes of two groups were compared, which included reflux esophagitis (RE) score, esophageal hiatal hernia, Hill grade score of gastroesophageal flap valve, upper esophageal sphincter (UES) pressure, DeMeester score, and reflux episodes. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:There were no significant differences in RE score and Hill grade score between TGERD group and RA group (0.0, 0.0 to 1.0 vs. 0.0, 0.0 to 1.8; 3.0, 2.0 to 3.0 vs. 3.0, 2.0 to 3.0) (both P>0.05). The detection rate of UES pressure less than 34 mmHg (1 mmHg=0.133 kPa) of RA group was higher than that of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60), and the difference was statistically significant ( χ2=4.596, P=0.032). The UES pressure of RA group was lower than that of TGERD group (51.7 mmHg, 23.6 mmHg to 70.1 mmHg vs. 62.0 mmHg, 37.4 mmHg to 77.4 mmHg), and the difference was statistically significant ( Z=-2.105, P=0.035). There were no significant differences in other parameters of HREM between TGERD group and RA group (all P>0.05). The detection rates of DeMeester score more than 14.7, acid exposure time more than 4.5% and total reflux episodes more than 73 episodes of RA group were all higher than those of TGERD group (41.7%, 25/60 vs. 23.3%, 14/60; 40.0%, 24/60 vs. 21.7%, 13/60; 38.3%, 23/60 vs. 20.0%, 12/60, respectively), and the differences were all statistically significant ( χ2=5.546, 4.728 and 4.881, all P<0.05). The total reflux episodes and weak acid gas reflux episodes of RA group were both higher than those of TGERD group (60 episodes, 43 episodes to 98 episodes vs. 52 episodes, 34 episodes to 69 episodes; 12 episodes, 6 episodes to 21 episodes vs. 9 episodes, 3 episodes to 14 episodes), and the differences were statistically significant ( Z=-2.323 and -2.053, both P<0.05). There were no significant differences in other parameters of 24 h pH-impedance monitoring between TGERD group and RA group (all P>0.05). Conclusion:Low UES pressure, abnormal esophageal acid exposure and increased reflux episodes, especially weak acid gas reflux episodes, may be more likely to induce RA.

Although the combination of surgery, radiotherapy and chemotherapy is the main methods of cancer treatment, it still fails to solve certain tumors, especially metastatic tumors. With the in-depth study of tumorigenesis and development mechanism, and the exploration and clinical application of tumor immunotherapy, the survival period of patients with malignant tumors has been significantly prolonged. Tumor immunotherapy has become an effective anti-tumor method by activating the body′s own immune system to achieve tumor suppression. The combination of chemotherapy and immunotherapy has a significant effect and has become a feasible solution for cancer treatment. The rationally designed nanomedicines can effectively combine chemical drugs and immunological preparations, and have become an effective delivery carrier basis and treatment means for clinically targeting tumor tissues, synergistic immune mechanisms to kill tumor cells, and treating tumors. In this paper, the types of multifunctional nanomedicines used in chemotherapy and various immunotherapies in recent years and their advantages in cancer therapy were reviewed.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.