mRNA vaccines and drugs enter host cells through delivery vectors and produce target proteins using the protein synthesis mechanism of cells. mRNA and target proteins can induce the body to produce innate immunity and adaptive immunity, and the target protein itself can also play a corresponding role. Tumor cells are inhibited and cleared under the above immune effects and target proteins. This article reviews the immunogenicity of mRNA, that is, the specific mechanism of stimulating the body to produce an immune response.At the same time, the main types of cells transfected by mRNA vaccine were briefly introduced. (1) Muscle cells, epidermal cells, dendritic cells and macrophages at the injection site; (2) immune cells in peripheral lymphoid organs;(3) liver cells and spleen cells, etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA),self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5'cap, 5'UTR, 3'UTR, ORF, 3'Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.
Anti-Inflammatory Agents ; Antioxidants ; Biological Availability ; Humans ; Rutin ; Solubility

Objective:To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions， and to verify syndrome stability and reliability. Method:A model of depression was established by exposing rats to chronic unpredictable mild stress （CUMS）， followed by body weight measurement， sugar water test， behavioral test， and brain 5-hydroxytryptamine（5-HT） detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale， Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency. Result:The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS （eight weeks of CUMS） group were significantly lower than those in the normal group （P<0.05）. According to the immunohistochemical results， the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group（P<0.05），which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats （six weeks after CUMS）of the CUMS group， and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week （eight weeks after CUMS），accounting for 70% of the total number. Thereafter， the number decreased gradually. The syndrome scores of the 14-， 16-， 18-， 20-， and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%， 70.7%， 54.8%， 50.4%， and 44.8%， which were graded as effective， marked effective， effective， effective， and effective， respectively. Conclusion:The age of 14-16 weeks（six to eight weeks after CUMS） is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.
Humans ; Intestinal Obstruction ; Postoperative Complications ; Quality of Life ; Rectal Neoplasms ; Retrospective Studies ; Syndrome ; Treatment Outcome

OBJECTIVE: To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit. METHODS: Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively. RESULTS: The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups (>0.05); the total score of MMSE after treatment was higher than that before treatment (both <0.05); compared before treatment, the short-term memory score was increased in the treatment group (<0.05), and the increasing range was superior to that in the control group (<0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both <0.05), and the reduction in the treatment group was less than that in the control group (<0.05); the differences of short-term memory score before and after treatment was significant between the two groups (<0.05). No adverse reaction occurred in the two groups. CONCLUSION The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.
Acupuncture Points ; Acupuncture Therapy ; Alzheimer Disease ; psychology ; therapy ; Case-Control Studies ; Electroacupuncture ; Humans ; Mental Status and Dementia Tests

BackgroundThe introduction of individualized abdominoperineal excision (APE) may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer.

MethodsFifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin (CRM) involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0.

ResultsFifty (89%) patients received preoperative chemoradiotherapy: 51 (91%) patients were treated with the sacrococcyx preserved; 27 (48%) patients with the levator ani muscle partially preserved bilaterally; 20 (36%) patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 (13%) patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 (4%) patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction (12%), perineal wound complications (13%), urinary retention (7%), and chronic perineal pain (5%). A positive CRM was demonstrated in 3 (5%) patients, and intraoperative perforations occurred in 2 (4%) patients. On multiple logistic regression analysis, longer operative time (P = 0.032) and more intraoperative blood loss (P = 0.006) were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow-up of 53 months (range: 30-74 months).

ConclusionWith preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes.

Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; pathology ; surgery ; Operative Time ; Perineum ; surgery ; Postoperative Complications ; Rectal Neoplasms ; pathology ; surgery ; Rectum ; surgery ; Retrospective Studies ; Treatment Outcome

BACKGROUNDBipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection. However, the mechanisms of bipolar electro-coagulation are not completely known. We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy.

METHODSTwenty-four patients were consecutively enrolled, and divided into three groups according to the date of admission. The regional cortical blood flow (rCBF), electrocorticography, the depth of cortex damage, and acute histological changes (H and E staining, neuronal staining and neurofilament (NF) staining) were analyzed before and after the operation. The t-test analysis was used to compare the rCBF before and after the operation.

RESULTSThe rCBF after coagulation was significantly reduced (P < 0.05). The spikes were significantly reduced after electro-coagulation. For the temporal cortex, the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03, 0.48 ± 0.06, 0.69 ± 0.06, 0.84 ± 0.09, 0.98 ± 0.08, 1.10 ± 0.11, 1.11 ± 0.09, and 1.22 ± 0.11 mm, respectively. Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer, external granular layer, and external pyramidal layer.

CONCLUSIONSThe electro-coagulation not only destroyed the neurons and NF protein, but also reduced the rCBF. We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges, and partially destroy the epileptic focus.

Adult ; Electrocoagulation ; methods ; Epilepsy ; surgery ; Epilepsy, Temporal Lobe ; surgery ; Female ; Humans ; Male ; Temporal Lobe ; surgery ; Young Adult

Objective To investigate the effect of vinpocetine on lear-ning and memory function and the expression of Nogo-A in the hippo-campus CA1 region of the rats with chronic cerebral ischemia.Methods The chronic cerebral ischemia rats model was induced by bilateral common carotid artery permanent occlusion. The rats were randomly divided into sham operation, model and experimental groups.Each group according to ischemic time was subdivided into 3 , 6 and 9 weeks groups. The rats in experimental group were injected vinpocetine intraperitoneally ( ip by 10 mg? kg -1 ) , once a day for consecutive 14 d.Cognitive func-tion of the rats were tested with the Morris water maze and the expression of Nogo -A was measured by immunohistochemistry and situ hibridiza-tion.Results After 6 weeks, the escape latency in the sham group, model group and the experimental group were ( 14.76 ± 4.34 ) , (33.23 ±3.42) , ( 27.74 ±5.30 ) s, respectively. The number of cross-platform were (6.88 ±2.64 ) , ( 3.13 ±1.81 ) , ( 5.38 ±1.85 ) times, respectively.Compared with model group, the average escape latency significantly shortened, the number that rats passed through the platform significantly increased ( P <0.05 ) , and the expression of Nogo-A protein and mRNA in hippocampal CA1 areas significantly increased ( P<0.05 ) in the experiment group at different time points. Conclusion Vinpocetine can improve the cognitive dysfunction of chronic cerebral ischemia rats which might be corre-lated to the neuroprotective effect of vinpocetine on neuronal by down-regulating the expressions of Nogo-A protein and mRNA.

OBJECTIVETo analyze the prevalence and onset of age of stroke in Chinese adults aged 35 years old and above.

METHODSData from the 2002 National Nutrition and Health Survey was used to analyze the prevalence of stroke by age, sex, regions, and the differences of onset of age of stroke among the alive patients.

RESULTStandardized prevalence of stroke in Chinese adults aged 35 years old and above was 1111.5 per 100,000, 1258.9 per 100,000 in male which was higher than female (959.3 per 100,000). The prevalence of stroke in urban (1544.8 per 100.000) was higher than that in rural (758.1 per 100,000). The standardized prevalence of stroke in the north (1479.3 per 100,000) was significantly higher than that in the south (719.6 per 100,000). The standardized prevalence of stroke in eastern, central and western region was 1469.0 per 100,000, 1085.4 per 100,000, 614.9 per 100,000, respectively. It is estimated that there were 5.627 million patients with stroke aged 35 years old and above in China in 2002. The age at onset of stroke in the alive patients was skewed distribution. Median was 60 years old. The first incidence of stroke within 60-age group accounted for 32.4%. The age at onset of stroke was no significantly different between male (60 years old, chi(2) = 0.00, P > 0.05) and female (60 years old). The median of the age at onset of stroke (61 years old) in urban was higher than that in rural (58 years old, chi(2) = 17.34, P < 0.01). The median in eastern region was higher than that in central and western regions (57 years old, chi(2) = 12.92, P < 0.01).

CONCLUSIONThe prevalence of stroke was significant different by sex and regions. Among the alive patients, more than half of their first incidence of stroke were before the age of sixties.

Adult ; Age of Onset ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prevalence ; Stroke ; epidemiology

The dominant gene Xa21 with broad-spectrum and high resistance to Xanthomonas oryzae pv. oryzae (Xoo) was transferred into C418, an important restorer line of japonica hybrid rice in China using double right-border (DRB) T-DNA binary vector through Agrobacterium-mediated transformation. 17 transgenic lines were Xa21-positive with high resistance to the race P6 of Xoo through PCR analysis and resistance identification, among the total 27 independent primary transformants (T0) obtained. The subsequent analysis of the T1 progenies of these 17 T0 lines through PCR-assisted selection and resistance investigation showed that four Xa21 transgenic T0 lines could produce selectable marker-free (SMF) progenies. The frequency of primary transformants producing SMF progenies was 15%. In addition, PCR analysis also revealed these SMF progenies did not contain vector backbone sequence, and they were named as SMF and vector backbone sequence-free (SMF-VBSF) Xa21 transgenic plants. The further molecular and phenotypic analysis of the T2 and T3 progenies testified the homozygous SMF-VBSF Xa21 transgenic plants were obtained with high resistance to Xoo.
DNA, Bacterial ; genetics ; Genetic Vectors ; Oryza ; genetics ; Plant Proteins ; genetics ; Plants, Genetically Modified ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Rhizobium ; genetics ; Transformation, Genetic ; Xanthomonas