Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

At present,reforming and innovating the public health talent training model are the challenges that the construc-tion of new medical in our country.Medical Immunology is the initial driving force in preventive medicine.Based on the course con-struction of Medical Immunology and centering on the core link of post competency of preventive medicine undergraduates,this study comprehensively reshapes the course system of Medical Immunology from the aspects of theoretical courses,practical courses,experi-mental courses,ideological and political courses and assessment methods,so as to provide reference for improving the teaching quality of preventive healthcare undergraduates.

At present,reforming and innovating the public health talent training model are the challenges that the construc-tion of new medical in our country.Medical Immunology is the initial driving force in preventive medicine.Based on the course con-struction of Medical Immunology and centering on the core link of post competency of preventive medicine undergraduates,this study comprehensively reshapes the course system of Medical Immunology from the aspects of theoretical courses,practical courses,experi-mental courses,ideological and political courses and assessment methods,so as to provide reference for improving the teaching quality of preventive healthcare undergraduates.

OBJECTIVE To clarify the components of volatile oil in branches and leaves of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii. METHODS The total volatile oil in leaves and branches of these plants were obtained by supercritical CO2 extraction. After that, the chemical composition of the total volatile oil was analyzed and identified by GC-MS, and the contents of different parts and varieties were compared. RESULTS The results showed that the highest oil yield of leaves was Rhododendron thymifolium(6.97%), and the highest oil yield of branches was Rhododendron anthopogonoides(20.53%). Thirty-five, eighty, fifty-eight and forty compounds were detected in the branch oil of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii respectively, among which Rhododendron capitatum was rich in compounds. Forty-eight, fifty-seven, sixty-two and fifty compounds were detected in the leaf oil, among which the compounds of Rhododendron anthopogonoides were the richest. Among the detected components, squalene(34.92%, 26.90%) was the highest content in the branches and leaves of Rhododendron anthopogonoides. 1-Eicosanol(26.79%) was the highest content in the branch oil of Rhododendron capitatum, and octadecyl acetate(42.32%) was the highest content in the leaf oil. The highest content of bisabola-3,10-diene-2-one(34.66%, 28.20%) was found in the branches and leaves of Rhododendron thymifolium, and 15-oxoETE(38.20%, 40.40%) was the highest content in the branches and leaves of Rhododendron przewalskii. The results showed that the contents of oil in branches and leaves of Rhododendron capitatum were quite different in different parts. In the comparison of different varieties, the compounds with the highest content of four rhododendrons were all different. CONCLUSION According to the difference of the content of active components of different rhododendrons and parts, the appropriate species and parts for purposeful development and utilization should be selected. The research results can provide scientific basis for rational development and utilization of Rhododendron resources.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To explore the effects of "rain classroom" wisdom teaching on geriatric students′ autonomous learning ability and self-efficacy.Methods:From June to August, 2021, 61 nursing students who practiced in the department of gerontology of the Second Xiangya Hospital, Central South University were selected as research subjects, and divided into experimental group (30 students) and control group (31 students) by random number table method. In the experimental group, wisdom teaching based on "Rain classroom" was carried out at the same time as conventional teaching, while in the control group, conventional teaching was carried out, and the teaching effect was evaluated by the independent learning ability measurement scale and academic self-efficacy scale of nursing students.Results:The score of autonomous learning ability of nursing students in the experimental group was 68.55 ± 11.06, and that in the control group was 74.29 ± 9.16. The difference between the two groups was statistically significant ( t = -2.01, P<0.05). The academic self-efficacy scores of nursing students in experimental group and control group were 52.27 ± 11.56 and 52.64 ± 9.28 respectively. There was no significant difference between the two groups ( P>0.05). Conclusions:The wisdom teaching of "rain classroom" improves the independent learning ability of geriatric nursing students, and attaches importance to the cultivation of self-efficacy of nursing students, and the improvement of self-efficacy needs further research.

Purpose: This study aimed to explore the role of the long non-coding RNA (lncRNA) RNA component of mitochondrial RNAase P (RMRP) in sepsis-induced acute kidney injury (AKI). Materials and Methods: Venous blood was collected from septic patients and healthy people. C57BL/6 mice who underwent cecal ligation and puncture (CLP) were used as in vivo models of septic AKI. Lipopolysaccharide (LPS)-induced HK-2 cells were employed as in vitro models of AKI. Flow cytometry analysis was conducted to detect cell apoptosis. Enzyme-linked immunosorbent assay and Western blot assays were used to detect levels of pro-inflammatory cytokines. Results: RMRP was upregulated in sera from patients with AKI and in LPS-induced cells. Knockdown of RMRP inhibited cell apoptosis and reduced production of inflammatory factors in LPS-induced cells, as well as alleviated AKI in CLP mice. RMRP facilitated inflammation by activating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. We found that microRNA 206 (miR-206) binds with and is negatively regulated by RMRP: miR-206 directly targets the 3’ untranslated region of DEAD-box helicase 5 (DDX5) and negatively regulates DDX5 expression. By binding with miR-206, RMRP upregulated DDX5 expression. Rescue assays revealed that overexpression of DDX5 counteracted the effect of RMRP inhibition on cell apoptosis and inflammatory response in LPS-induced cells. Conclusion The lncRNA RMRP contributes to sepsis-induced AKI through upregulation of DDX5 in a miR-206 dependent manner and through activation of NLRP3 inflammasome. This novel discovery may provide a potential strategy for treating AKI.

A 53-year-old male patient received intramuscular injection of diclofenac sodium and lidocaine injection 2 ml for abdominal pain. After one hour of medication, the patient developed upper abdominal discomfort, chest tightness, shortness of breath, sweating, and slight cyanosis of lips. Oxygen inhalation was given immediately. Electrocardiogram monitoring showed blood pressure 105/60 mmHg, heart rate 125 beats/min, and blood oxygen saturation 0.75. His peripheral blood glucose could not be detected. Glucose supplement and hormone therapy were given immediately. About 30 minutes later, the patient developed unconsciousness, no pulsation of the main artery, and cardiac and respiratory arrest. Cardiopulmonary resuscitation and other treatment measures were given immediately. However, the patient did not return to spontaneous heartbeat and breathing and was declared dead. It was considered that the patient′s severe hypoglycemia might be related to diclofenac sodium and lidocaine.

A 53-year-old male patient received intramuscular injection of diclofenac sodium and lidocaine injection 2 ml for abdominal pain. After one hour of medication, the patient developed upper abdominal discomfort, chest tightness, shortness of breath, sweating, and slight cyanosis of lips. Oxygen inhalation was given immediately. Electrocardiogram monitoring showed blood pressure 105/60 mmHg, heart rate 125 beats/min, and blood oxygen saturation 0.75. His peripheral blood glucose could not be detected. Glucose supplement and hormone therapy were given immediately. About 30 minutes later, the patient developed unconsciousness, no pulsation of the main artery, and cardiac and respiratory arrest. Cardiopulmonary resuscitation and other treatment measures were given immediately. However, the patient did not return to spontaneous heartbeat and breathing and was declared dead. It was considered that the patient′s severe hypoglycemia might be related to diclofenac sodium and lidocaine.

Objective : To evaluate the safety and immunogenicity of a split-virion quadrivalent influenza vaccine. Methods : The healthy people aged three years or over in Wuyang County and Xiping County of Henan Province were divided into the experimental group, control group 1 and control group 2, and were vaccinated with split-virion quadrivalent influenza vaccines, split-virion trivalent influenza vaccines (without B/Victoria) and a split-virion trivalent influenza vaccines (without B/Yamagata) , respectively. The hemagglutination inhibition (HI) antibodies were detected before and after immunization. The incidence rate of adverse events following immunization (AEFI) , HI antibody positive conversion rate, the protection rate of HI antibodies and the growth of geometric mean titer (GMT) were calculated and compared with the standard of Food and Drug Administration (FDA). Results: Totally 2 924 people were recruited, with 975 in the experimental group, 974 in the control group 1 and 975 in control group 2. The incidence rate of AEFI in the experimental group was 11.7%, higher than 7.9% in control group 1 and 8.8% in control group 2 (P < 0.05) during 30 minutes and 8 days after inoculation. The positive conversion rates of HI antibodies of H1N1, H3N2, By and Bv in the experimental group were 78.5%, 53.3%, 78.3% and 62.9%, respectively. The rate differences of the positive conversion rates of HI antibodies of By between the experimental group and control group 2, and of Bv between the experimental group and control group 1 were 42.1% (95%CI: 38.0%-46.2%) and 33.2% (95%CI: 28.9%-37.5%) , with both lower limits of 95%CI more than -0.10. The GMT increase of HI antibodies was more than 2.5 times in the three groups. The protective rates of HI antibodies of H1N1, H3N2, By and Bv in the experimental group were 87.7%, 98.7%, 93.6% and 77.2%, respectively. The protective rates of HI antibodies of By in control group 2 and Bv in control group 1 were 71.1% and 51.0%, both lower than those in the experimental group (P < 0.05). Conclusions After the inoculation of the quadrivalent influenza vaccine, the positive conversion rates (>40%) , protection rates (>70%) and GMT increase (>2.5 times) of HI antibodies of H1N1, H3N2, By and Bv all meet the quality standards of FDA. The safety and immunogenicity of the quadrivalent influenza vaccine are not inferior to those of the trivalent influenza vaccine.