Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dys-function in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recov-ery of patients.Methods This study has been reviewed and approved by the Ethics Committee,and informed consent has been obtained from patients.A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion,and 70 eligible patients from Hospital of Stomatology,Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group(35 patients in each group).The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery,such as shoulder mobility and coordination training and small range of motion training of the neck,while the test group took part in a rehabilitation training program that included familiarization maneuver training,protective rehabilitation,exercise rehabilitation,and resistance training in the following four stages:preoperative,postop-erative general anesthesia and awake until the removal of stitches,the removal of stitches until 6 weeks after surgery,and 6 weeks after surgery until 1 year after surgery.The frequency of training in both groups was at least 3 days per week,and the length of each training session was 10-15 min.The intensity of exercise was 2-3 points on the Borg Conscious Ex-ercise Intensity Scale(i.e.,mild-to-moderate tachypnea or fatigue).The neck dissection injury index(NDII)was used to evaluate the quality of life related to shoulder joint function at four time points:preoperative,postoperative 3 months,postoperative 6 months,and postoperative 12 months.The higher the score,the better the quality of life.Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up.At 3 and 6 months postopera-tive,the NDII of the test group was significantly higher than that of the control group[3 months postoperative:test group(93.48±9.36)vs.control group(80.00±11.34)(P＜0.001),6 months postoperative:test group(98.21±4.76)vs.control group(90.70±9.12)(P＜0.001)];12 months after surgery,the NDII of the test group(97.23±4.88)was still higher than that of the control group(96.33±4.49),but the difference was not statistically significant(P=0.458).The difference in NDII scores among subjects at 3,6,and 12 months after surgery was statistically significant in each group(P＜0.001).Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients'shoulder joint function within 6 months after surgery.

Objective:To understand the current situation of psychological crisis vulnerability among elderly individuals with multimorbidity and analyze the factors that influence it, to provide insights for improving their coping abilities.Methods:A cross-sectional survey design was conducted at Renmin Hospital of Wuhan University from May 1 to November 30, 2022.The attitudes toward aging, sense of meaning of life, and vulnerability to psychological crisis were analysed among outpatients and inpatients.Statistical analysis was performed on the questionnaire results, and the influencing factors of vulnerability to psychological crisis in elderly patients with co-morbidities were analyzed using one-way linear regression and multivariate linear regression.Additionally, the correlation between aging attitudes, sense of meaning of life, and vulnerability to psychological crisis was examined using Pearson correlation analysis.Results:A total of 685 questionnaires were distributed, and 602 valid questionnaires were collected, resulting in a valid recovery rate of 87.9%.The total score for the sense of meaning of life in elderly co-morbid patients was(39.2±8.3), while the total score for aging attitudes was(80.2±13.5).The total score for psychological crisis vulnerability was(69.4±12.8), indicating a medium-high level of vulnerability.The results of multiple linear regression analysis revealed that the factors influencing psychological crisis vulnerability in elderly multimorbidity, in descending order, were residence status, economic situation, marital status, age, type of chronic disease, and hospitalization history in the past six months.Psychological crisis vulnerability in elderly multimorbidity showed a negative correlation with the sense of meaning of life and the attitude of aging( r=-0.315, -0.264, both P<0.01), while the attitude of aging exhibited a positive correlation with the sense of meaning of life( r=0.515, P<0.01). Conclusions:The vulnerability of elderly individuals with multimorbidity to psychological crises is influenced by several factors.Healthcare professionals should prioritize individuals who are elderly, residing in nursing institutions, widowed, financially disadvantaged, experiencing multiple illnesses, and not currently hospitalized.

Objective:To evaluate the relationship between spinal cord cytoplasmic activation/proliferation-associated protein-1 (Caprin-1)-mediated expression of calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and pain perception in mice.Methods:Nestin CreERT2 mice and Caprin-1 flox/flox mice were hybridized to obtain Nestin CreERT2; Caprin-1 flox/flox homozygous mice. The mice were divided into 2 groups ( n=5 each) using a random number table method: Nestin CreERT2; Caprin-1 flox/floxsolventcontrol group (SC group) and Caprin-1 gene knockout group (KO group). Tamoxifen 100 mg/kg was intraperitoneally injected for 5 consecutive days to generate inducible knockout of the Caprin-1 gene in KO group. The mechanical paw withdrawal threshold was measured at day 1 before and day 5 after the end of administration. Then the mice were sacrificed, and L 4-6 segments of the spinal cord were removed for determination of the expression of Caprin-1 and CaMKⅡα protein and mRNA (by Western blot or real-time quantitative polymerase chain reaction) and co-expression of Caprin-1 with CaMKⅡα (by immunofluorescent double staining). Results:Compared with SC group, the mechanical paw withdrawal threshold was significantly increased at 5 days after the end of tamoxifen administration, the expression of Caprin-1 and CaMKⅡα protein and mRNA was down-regulated ( P<0.05), and the co-localization expression of Caprin-1 and CaMKⅡα in the spinal dorsal horn was down-regulated in KO group. Conclusions:Caprin-1 is involved in the development of pain perception by promoting CaMKⅡα expression.

Objective:To investigate the synergistic antitumor effect of pyrotinib in combination with 5-fluorouracil(5-Fu)on human epidermal growth factor receptor 2(HER2)positive breast cancer cells and its underlying molecular mechanism. Methods:HER2 positive breast cancer cells were screened by Western blotting.HER2 positive SKBR-3 and BT474 cells were treated with pyrotinib and 5-Fu individually or in combination for the following experiments.MTT assay was used to assess the effect of different drugs on the proliferation of the treated cells,and the combination index(CI)values were calculated using Combidrug software.Colony formation assay was used to evaluate the effect of different drugs on the colony-forming ability of the treated cells.FCM assay was used to analyze the effect of different drugs on the apoptosis rate and cell cycle of the treated cells.Western blotting was used to examine the effect of different drugs on the expression levels of proteins in the proliferation-and apoptosis-related signaling pathways.SKBR-3-cell-based tumor xenograft model was established using BALB/c nude mice.After treatment with pyrotinib and 5-Fu individually or in combination,the growth profiles of the xenograft tumors were recorded and the expression levels of proteins in the proliferation-and apoptosis-related signaling pathways were examined in the tumor tissues. Results:HER2 positive breast cancer cell lines SKBR-3 and BT474 were selected for further experiments after screening.The proliferation SKBR-3 and BT474 cells could be inhibited after treatment with pyrotinib and 5-Fu individually or in combination(all P＜0.05).Compared with pyrotinib or 5-Fu single drug treatment,pyrotinib in combination with 5-Fu had higher inhibition rate on the proliferation of SKBR-3 and BT474 cells with a Cl value of＜1,indicating the synergistic effect of pyrotinib and 5-Fu.In addition,in contrast to pyrotinib or 5-Fu single drug treatment,there was a further decrease in the number of colonies formed,increase in apoptosis rate,and increase in the percentage of G0/G,cells in SKBR-3 and BT474 cells after treatment with pyrotinib in combination with 5-Fu(all P＜0.01).Animal experiment results showed that the growth rate of xenograft tumors in mice treated with pyrotinib in combination with 5-Fu was significantly slower than that of the single-drug treated mice(P＜0.05).Western blotting analysis showed that the expression levels of HER2,HER4,AKT and phosphorylated ERK were significantly decreased after treatment with pyrotinib in combination with 5-Fu both in vitro and in vivo(all P＜0.01),indicative of the blockage of proliferation-related signaling pathways.Meanwhile,analysis of the apoptosis-related proteins revealed a decrease in the expression levels of caspase 3,poly ADP-ribose polymerase(PARP),and Bcl-2(all P＜0.01),while an increase in the expression levels of cleaved-caspase 3,cleaved-PARP,and p21(all P＜0.01). Conclusion:Pyrotinib and 5-Fu had synergistical antitumor effect on HER2 positive breast cancer cells,and the underlying mechanism may be related to the blockage of proliferation-associated signaling pathways and the induction of apoptosis and cell cycle arrest.

Objective:To explore the effects of stepwise acute pain management on acute pain and post-traumatic stress disorder (PTSD) in children with burns.Methods:From November 2018 to December 2019, 196 children with burns who were admitted to West China Hospital of Sichuan University and met the inclusion criteria were enrolled in the prospective randomized controlled study. The children were divided into traditional pain management group (97 children, 51 males and 46 females, aged 1 to 6 years) and stepwise pain management group (96 children, 55 males and 41 females, aged 1 to 6 years) according to the random number table. Children in traditional pain management group were treated with traditional acute pain care, while the children in stepwise pain management group were treated with stepped acute pain management (moderate pain was treated with oral administration of acetaminophen sustained-release dry suspension at the dose of 10 to 15 mg/kg once every 4 to 6 hours, and severe pain was treated with morphine intravenous injection at the dose of 0.1 to 0.2 mg/kg once every 4 hours) on the basis of traditional acute pain care after admission. The COMFORT behavior scale was applied to compare the resting pain levels of children in the two groups within post injury day (PID) 3 (1, 9, and 17 o'clock each day). The adverse reactions of children in the stepwise pain management group during the treatment period were recorded. The occurrence of PTSD within one month after injury was evaluated in both groups by the revised PTSD scale. Data were statistically analyzed with independent sample t test, Bonferroni correction, analysis of variance for repeated measurement, chi-square test, Wilcoxon rank sum test, and Fisher's exact probability test. Results:The pain scores of children in stepwise pain management group were significantly lower than traditional pain management group at 1, 9, and 17 o'clock on PID 1, 1, 9, and 17 o'clock on PID 2, and 1, 9, and 17 o'clock on PID 3 ( t=2.71, 3.44, 4.05, 4.18, 4.08, 4.19, 4.25, 3.69, 3.71, P<0.05 or P<0.01). The pain scores of children in both groups showed a decreasing trend over time. Of the 96 children in stepwise pain management group, 84 children were treated with oral administration of acetaminophen sustained-release dry suspension, and 12 children were treated with morphine intravenous injection. No adverse reaction occurred during the treatment period. The incidence of PTSD of children in stepwise pain management group within 1 month after injury was 3.12% (3/96), which was significantly lower than 14.43% (14/97) in traditional pain management group, P<0.05. Conclusions:The stepped acute pain management can relieve the acute pain and reduce the incidence of PTSD in children with burns.

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes

【Objective】 To investigate the hepatitis E virus(HEV) infection among voluntary blood donors in Liuzhou, Guangxi. 【Methods】 Qualified blood donations in Liuzhou from October to November 2019 were tested for anti-HEV IgG and IgM and.HEV antigen. HEV RNA test was performed on samples positive for HEV antigen and/or anti-HEV IgM. and the test results were analyzed statistically. 【Results】 The seroprevalence rates of HEV antigen and anti-HEV IgG and IgM among 5 751 qualified donations were 0, 26.03% (1497/5 751), and 1.67% (96/5 751), respectively.None of the 91 anti-HEV IgM positive samples was positive for HEV RNA, whereas 60.41% of anti-HEV IgM positive samples were anti-HEV IgG positive. The HEV antibody prevalence varied significantly by gender, age, and nationality (P<0.05). 【Conclusion】 The prevalence of anti-HEV IgG / IgM among blood donors in Liuzhou was higher than that in other domestic regions. Significant increase in HEV antibody prevalence was observed among ethnic minorities, such as Miao and Dong, and age group of more than 45 years.Follow-up studies with larger sample size could be conducted to estimate potential risks of HEV transmission by blood transfusion, which may provide references for selective screening of HEV infection marker among high-endemic population.

Objective To investigate the effects of calycosin, formononetin, calycosin-7-glucoside and ononin on PC 12 cells differentiation. Methods PC 12 cells were cultured and treated with different concentrations of nerve growth factor (NGF), calycosin, formononetin, calycosin-7-glucoside and ononin for 5 days, once a day, 3 times in a row. The neurite outgrowth of PC 12 cells was observed and the expression of β III-tubulin were measured by immunofluorescence. Results Compared with the vehicle group, neurite outgrowth and the expression of β III tubulin in PC 12 cells had not promoted by calycosin, formononetin, calycosin-7-glucoside and ononin (0.01-10.00 μmol/L). Conclusion PC 12 cells differentiation could not be induced by calycosin, formononetin, calycosin-7-glucoside and ononin.