To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

Objective To evaluate the role of autophagy in the treatment of neuropathic pain(NP)with hydrogen-rich saline.Methods Forty adult male Sprague-Dawley rats with successful intubation were randomly divided into 5 groups(n= 8)using a random number table:the sham operation group(group S),the neuropathic pain group(group C),the hydrogen-rich saline group(group H),the autophagy inhibitor group(group M)and the hydrogen-rich saline + autophagy inhibitor group(group HM).There were 8 rats in each group.The NP model was established by chronic constriction of the sciatic nerve(CCI)in rats.The autophagy inhibitor 3-methyladenine(3-MA)was intraperitoneally injected with 30μg/kg in the group M and the group HM.The hydrogen-rich saline(0.6 mmol/L)was intraperitoneally injected with 10 mL/kg in the group H and the group HM.The other groups were intraperitoneally injected with the same amount of normal saline twice a day for 7 consecutive days.Paw withdrawal threshold to mechanical stimulation(MWT)and paw withdrawal latency to thermal stimulation(TWL)were measured at 1 day before and 1,3,5,7 and 14 days after modeling(T0-T5).After the last measurement of pain threshold,the L4-L6 segment of spinal cord was removed for determination of the expression of autophagy-related proteins microtubule-associated protein light chain 3(LC3)Ⅱ,Beclin-1 and p62 proteins by Western blot assay.The expression levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in spinal cord tissue were detected.Results Compared with the group S,MWT and TWL were decreased in the group C at T2-5,the expression levels of LC3 Ⅱ,Beclin-1 and p62 were increased,SOD activity was decreased,and MDA content was increased at T5(P＜0.05).Compared with the group C,MWT and TWL were increased in the group H at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were increased,p62 protein expression levels were decreased,SOD activity was increased,and MDA content was decreased at T5(P＜0.05).MWT and TWL were decreased in the group M at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were decreased,p62 protein expression levels were increased,SOD activity was decreased,and MDA content was increased at T5(P＜0.05).Compared with the group M,MWT and TWL were increased in the group HM at T2-5,LC3 Ⅱ and Beclin-1 protein expression levels were increased,p62 protein expression levels were decreased,SOD activity was increased,and MDA content was decreased at T5(P＜0.05).Conclusion Hydrogen-rich saline can alleviate neuropathic pain and inhibit oxidative stress in spinal cord in rats,and the mechanism may be related to the increase of autophagy.

Objective To compare the effectiveness and safety of ketamine and etomidate for rapid sequential intubation. Methods Randomized controlled trials and cohort studies with ketamine and etomidate for RSI in patients with acute and critical illnesses published by China National Knowledge Infrastructure, Wanfang Data, VIP Network, PubMed, Embase, Cochrane Library and Clinicaltrials.gov from the date of database creation to May 1, 2023 were searched by computer. The literatures were screened according to inclusion and exclusion criteria, and the data of literatures were also extracted for quality assessment. Meta-analysis was performed by RevMan 5.3 software. Results A total of 15 literatures with 20 839 patients were included, including 3 RCT studies and 12 cohort studies. Meta-analysis showed that there were no significant differences in the success rate of primary intubation (RR=0.99, 95 %CI, 0.98 to 1.00, P=0.10), incidence of cardiac arrest (RR=1.00, 95 %CI, 0.62 to 1.62, P=0.99), time of mechanical ventilation (MD=0.33, 95 %CI, -0.34 to 1.01, P=0.33), and mortality rate (RR=1.05, 95 %CI, 0.95 to 1.16, P=0.31) between the ketamine group and the etomidate group, but the incidence of adrenal insufficiency (RR=0.54, 95 %CI, 0.41 to 0.70, P < 0.001) and ICU stay (MD=-0.44, 95 %CI, -0.70 to -0.18, P=0.001) in the etomidate group were significantly lower and shorter than those in the ketamine group, while the incidence of hypoxemia was significantly higher in the etomidate group (RR=1.50, 95 %CI, 1.27 to 1.79, P < 0.001). Conclusion During the process of RSI with sufficient preoxygenation, ketamine is a safe and effective alternative drug, and compared with etomidate, it has a lower incidence of adrenal insufficiency and shorter ICU stay.

In recent years， neurotoxicity caused by traditional Chinese medicine （TCM） has frequently occurred and has become one of the important factors restricting the development and application of TCM. TCM contains active components and its dosage-effect relationship is the key to determine its pharmacological activity and toxic effects. Among them， the endogenous toxic components include alkaloids， glycosides， diterpenoids， animal and plant toxic proteins and heavy metals， and so on； exogenous toxic components mainly refer to some harmful elements and pesticide residues during the cultivation， processing， transportation and storage of medicinal materials that are not synthesized by themselves. Effect on the processes such as oxidative stress， inflammation， ion exchange， and energy metabolism may be important mechanisms of TCM-induced neurotoxicity. Neural cells， myelin cells， axons and neurotransmitter systems are common targets of TCM-induced neurotoxicity. In the future， we can use modern research methods and big data mining means to establish a safety evaluation mode of “toxic symptoms-poisoning dose-toxic original agent-detoxification scheme” with the basic component group of toxic substances as the core， so as to provide support for development and clinical intervention of neurotoxic traditional Chinese medicine.

Objective:To explore the role of activated CD4 + T cells in cardiac remodeling after myocardial infarction (MI). Methods:① Experiment in vitro: naive CD4 + T cells were isolated in mouse spleen, and then stimulated with plate-bound anti-CD3 and anti-CD28 for 48 hours. Exosomes isolated from the supernatant of activated CD4 + T cells were incubated with cardiac fibroblasts (CFs) for 48 hours, and then the ability of CFs proliferation, migration and differentiation were detected by cell counting kit-8 (CCK-8) assay, Transwell assay, and immunofluorescence assay. ② Experiment in vivo: 40 male C57 mice were divided into 4 groups according to random number table method, including control group (Ctrl group), sham operation group (Sham group), MI group, and exosome treatment group (MI+Exo group), with 10 in each group. The mice model of MI was established by ligating the left anterior descending coronary artery. In MI+Exo group, 40 μg/d exosomes were injected intravenously into the tail after modeling. Cardiac function and cardiac fibrosis post-MI were assessed by echocardiography and quantitative polymerase chain reaction (qPCR) at 4th week. Results:① In vitro: exosomes derived from activated CD4 + T cells significantly promote CFs proliferation, migration and differentiation [proliferation ability ( A value): 0.31±0.01 vs. 0.21±0.01, migration capability (cells/MP): 79.20±3.34 vs. 48.80±2.13, differentiation ability (α-smooth muscle actin, α-SMA; fluorescence intensity): 1.56±0.03 vs. 1.00±0.02, all P < 0.05]. ② In vivo: echocardiographic analysis showed that exosomes derived from activated CD4 + T cells aggravated the deterioration of cardiac dysfunction post-MI than MI group, as indicated by left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased significantly [LVEF: 0.185±0.008 vs. 0.257±0.022, FS: (9.72±1.72)% vs. (14.08±1.08)%, both P < 0.05], left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) increased significantly [LVEDD (mm): 5.43±0.29 vs. 4.62±0.35, LVESD (mm): 4.94±0.12 vs. 3.69±0.29, both P < 0.05]. Additionally, qPCR showed that exosomes derived from activated CD4 + T cells remarkably promoted myocardial fibrosis post-MI than MI group, as indicated by the mRNA expression of α-SMA, collagens (Col1a1, Col3a1) in MI+Exo group was significantly higher than that in MI group [α-SMA (2 -ΔΔCT): 4.72±0.89 vs. 3.58±0.78, Col1a1 (2 -ΔΔCT): 6.59±0.56 vs. 4.23±0.42, Col3a1 (2 -ΔΔCT): 13.40±1.03 vs.4.96±0.36, all P < 0.05]. Conclusion:Activated CD4 + T cells promote cardiac remodeling following MI through transferring exosomes to CFs.

Objective: To explore the impact of function of mobile phone use on self-perceived stress and mobile phone addiction of high vocational students, and the mediating role of coping styles between different mobile phone functions and mobile phone addiction. Methods: A total of 911 participants in two vocational colleges in Wuhan and Liaocheng were investigated by using convenient sampling method. Smartphone Usage, Simplified Coping Style Questionnaire, and Stress subscale of Depression-Anxiety-Stress Scale(short version) were administered to participants. Results: Female students scored significantly higher on mobile phone social features (4.77±1.06) than males( t =2.05， P =0.04), while males scored significantly higher on MPATS and DASS-S, Negative Coping Style subscales than females( P <0.01). The social function of the mobile phone was positively related to the positive coping styles( r =0.17, P <0.01). The game features of mobile phone were positively related to negative coping styles, stress and mobile addiction( P <0.01). Negative coping style could positively predict stress and mobile phone addiction( β =0.53, 0.50, P <0.01). Negative coping styles and stress had significant chain mediation effects in nonsocial functions and mobile phone addiction(95% CI =0.06-0.24, P <0.01). Conclusion Students of vocational college who often use cellphone not for social purpose have higher self-perceived stress. The game function of mobile phones had an adverse effect on the physical and mental health of vocational students. Negative coping style is a powerful predictor of stress and mobile phone addiction.

Objective:To analyze the epidemiological and etiological characteristics of a dengue fever outbreak in Hunan province in 2018.Methods:Real-time PCR assay was performed for the laboratory diagnosis of 8 suspected dengue fever cases. Etiological surveillance was performed in 186 suspected dengue fever cases and fever cases who had close contacts with dengue fever patients. C6/36 cells was used for the virus isolation from acute phase serum. By sequencing the full length of E genes of 15 dengue virus strains, phylogenetic analysis was performed based on the sequences obtained, including reference sequences from the NCBI GenBank database, the serotypes and gene subtypes of the virus were analyzed to trace the possible source of transmission. An emergency monitoring of vector density and a retrospective survey of sero-epidemiology in healthy population were conducted in the epidemic area.Results:In the serum samples of 8 suspected patients, 6 were dengue virus RNA positive, and 4 were NS1 antigen positive. In 186 suspected patients, 96 were dengue virus nucleic acid, NS1 antigen or antibody positive in etiological test. A total of 64 dengue virus strains were isolated. The phylogenetic analysis showed that all the dengue virus strains belonged to type 2, which might be from Guangdong or Zhejiang provinces. The Bretub index was up to 65, indicating an extremely high risk of transmission. The positive rate of the dengue virus IgG antibody was 0.53%(2/377) in retrospective survey of 377 healthy people.Conclusion:The field epidemiologic and the molecular genetics analyses showed the outbreak of dengue fever in Hunan in 2018 was caused by imported cases and dengue virus 2.

Objective:To confirm the first imported Chikungunya fever (CHIK) epidemic in Hunan province.Methods:Serum samples of patients and colleagues were collected. The nucleic acids of Dengue virus (DENV), Yellow fever virus (YFV), Chikungunya virus (CHIKV) were detected by real- time fluorescent quantitative PCR. The positive PCR products were sequenced. Phylogenetic tree was constructed.Results:The serum samples of the patient and one of the five colleagues were positive for CHIKV. The Blast comparison of gene sequence showed 99% homology with CHIKV sequences. The infected CHIKV belonged to ECSA genotype in the phylogenetic tree.Conclusions:The first imported CHIK epidemic in Hunan province was confirmed through the epidemiological survey and etiologic detection.

Objective To analyze the efficacy and safety of tetrandrine in the adjuvant treatment of relapsed/refractory acute leukemia (except M3).Methods A total of 58 patients with relapsed/refractory acute leukemia (except M3) admitted to six tertiary hospitals in Jiangsu Province from January 2015 to December 2017 were included in this study.The tetrandrine-adjuvant standard chemotherapy regimen and standard chemotherapy regimen were given to treatment and control groups respectively.There were 17 and 41 patients in treatment and control groups.The treatment group was given tetrandrine for 5 days before the use of standard chemotherapy.The dose of tetrandrine was 4 mg ·kg-1 ·d-1,and patients had continuous oral administration of 5 days.After that,the patients in the treatment group started chemotherapy immediately.On the other side,the control group received standard chemotherapy without any other multidrug reversal medicine.Then the clinical efficacy and safety outcomes in both groups were analyzed.Results In the treatment group,5,3,and 9 cases achieved complete remission (CR),partial remission (PR),and nonremission (NR) respectively,and the total effective (CR+PR) rate was 47.06 ％ (8/17);in the control group,14,10,and 17 cases achieved CR,PR,and NR,and the total effective rate was 58.54 ％ (24/41).There was no significant difference in the total effective rate between the two groups (x2 =0.64,P =0.424).There was no significant difference in the efficacy between the two groups of patients with different genders (P ＞ 0.05).When the disease duration was 6-11 months,the difference of efficacy between the two groups was statistically significant (P =0.041).There was no significant difference in the proportion of myeloid leukemia cells,white blood cell count,platelet count,red blood cell count,and hemoglobin between the two groups before and after treatment (all P ＞ 0.05).There was no significant difference in clinical safety indicators (urine,faecal routine,liver and kidney function,and electrocardiogram) between the two groups (all P ＞ 0.05).Conclusions Tetrandrine is more effective in patients with relapsed/refractory acute leukemia (except M3) with shorter duration of disease.Compared with chemotherapy alone,the clinical efficacy of adding tetrandrine in chemotherapy cannot be considered superior to the former.

Objective: To make etiological diagnosis and evaluate the protective effects of post-exposure prophylaxis(PEP) in an event of one dog injured seven persons. Methods: Direct immunofluorescence assay (DFA) and nested polymerase chain reaction (PCR) were employed to detect nucleoprotein and nucleoprotein(N) gene of rabies virus in the brain tissues of the dog, the positive samples were sequenced for the full length of N gene of rabies virus, then the homology of the N gene of rabies virus was analyzed after the phylogenetic tree was constructed. Rapid fluorescent focus inhibition test (RFFIT) was applied to detect the rabies virus neutralizing antibodies(RVNA) on day 0, 14 and 40 after PEP. Results: The cerebral, cerebellar and hippocampal tissues were positive by DFA and nested PCR. The phylogenetic tree indicated the rabies virus belonged to the rabies virus genotype I. The homology of the nucleotide and amino acid of the rabies virus N gene were over 86% with the vaccine strains. The titer of the RVNA increased significantly from the day 0 to day 14 after PEP, the lowest was 5.78 IU/ml and the highest was 26.15 IU/ml. On the day 40, the highest RVNA titer was 51.96 IU/ml. No rabies cases occurred in a one year follow-up visit. Conclusions Normative PEP can effectively prevent the occurrence of rabies cases.