Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P＜0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P＜0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P＜0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.

Objective To analyze the administrative penalties for radiation diagnosis and treatment in Xuzhou, China, 2018—2021, investigate the key illegal behaviors in radiation diagnosis and treatment, and provide a basis for effective supervision with targeted measures. Methods A total of 142 cases of administrative penalties were analyzed for the year of the case, the undertaker, the basic information of the subjects, the amount of penalty, and the specific illegal facts. Results From 2018 to 2021, the case number of administrative penalties for radiation diagnosis and treatment in Xuzhou was relatively stable. The cases were mainly undertaken by the municipal health supervision institution, while the number of cases handled by basic-level health supervision institutions was increasing. The administrative penalties were mainly imposed on persons and primary or non-classified medical institutions. Common illegal behaviors included occupational health management of radiation workers and personal protection during medical exposure. Conclusion We should focus on strengthening the publicity and supervision of personal protection in occupational health management and medical exposure, continue to improve the law enforcement ability of basic-level radiation health supervisors, develop a standardized management system for radiation diagnosis and treatment, innovate the supervision mode and radiation hazard notification mode, promote the “Internet + ” informatization supervision, and recommend to improve and revise radiation-related laws and regulations.

Single-cell transcriptome sequencing (scRNA-seq) can resolve the expression characteristics of cells in tissues with single-cell precision, enabling researchers to quantify cellular heterogeneity within populations with higher resolution, revealing potentially heterogeneous cell populations and the dynamics of complex tissues. However, the presence of a large number of technical zeros in scRNA-seq data will have an impact on downstream analysis of cell clustering, differential genes, cell annotation, and pseudotime, hindering the discovery of meaningful biological signals. The main idea to solve this problem is to make use of the potential correlation between cells and genes, and to impute the technical zeros through the observed data. Based on this, this paper reviewed the basic methods of imputing technical zeros in the scRNA-seq data and discussed the advantages and disadvantages of the existing methods. Finally, recommendations and perspectives on the use and development of the method were provided.
Cluster Analysis ; Transcriptome

Objective:To investigate the efficacy of a SARS-CoV-2 recombinant protein vaccine as a booster dose.Methods:A new immunogen, namely RBD-sc-trimer, was designed by tandem repeating of single receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein to mimic the trimeric form of RBD presented by the virus. The RBD-sc-trimer protein was expressed as a His-tagged fusion protein using a baculovirus expression system and purified by nickel affinity column. The purified protein was identified by Western blot. Its in vitro binding activity to human angiotensin converting enzyme 2 (hACE2) was analyzed by ELISA. The immunogenicity of RBD-sc-trimer as well as RBD proteins of other forms including RBD dimer (RBD-Fc), RBD monomer (RBD) and S protein trimer (S trimer) as a booster dose was evaluated in BALB/c mice. Results:In terms of both binding and neutralizing antibodies against SARS-CoV-2, RBD-sc-trimer showed an immunogenicity that was superior to that of RBD-Fc and RBD and close to the level of S trimer. The antibody response induced by RBD-sc-trimer was characterized as Th1-biased. Moreover, it displayed a stronger cross-neutralization activity against SARS-CoV-2 Beta, Delta and Omicron variants. The titer of neutralizing antibody against Omicron induced by RBD-sc-trimer only decreased by 9.1 folds relative to the prototype strain, while the antibody response induced by RBD-Fc and S trimer decreased by 68.4 and 70.8 folds, respectively.Conclusions:The recombinant protein, RBD-sc-trimer, which was capable of eliciting stronger humoral response in mice as a booster dose and showed the superiority in raising cross-reactive antibodies against SARS-CoV-2 variants over non-trimeric RBD forms, should be considered as an optimal immunogen for the development of more effective SARS-CoV-2 vaccines.

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People’s Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.

Ninety eight patients with chronic hepatitis B (CHB) admitted to Department of Infectious Diseases, Yongkang First People′s Hospital from January 2017 to June 2018 were randomly divided into two groups. On the basis of entecavir+dicyclool treatment, patients in control group (48 cases) received health education and weekly telephone follow-up from the nurses, while patients in intervention group (50 cases) received health guidance from doctors and psychological counseling and communication from the nurses. All patients were followed up for 8 weeks. The illness perception, negative emotions, quality of life, and medication compliance were evaluated with the Revised Illness Perception Questionnaire (IPQ-R), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), SF-36 and Morisky Medication Adherence Scale (MMAS-8) in two groups, respectively. The results showed that, after 8 weeks, the disease identity, serious consequences, treatment control and disease correlation; SAS and SDS scores; physiological function, emotional function, energy and social function were significantly improved in control group( t=2.30, 3.45, 2.35, 2.23, 5.04, 6.03, 2.03, 2.79, 2.02, 2.34, all P<0.05). All dimension of illness perception; SAS and SDS scores; physiological function, physiological function, emotional function, energy, mental health, social function and general health were also improved significantly in intervention group ( t=4.06, 5.44, 6.91, 8.53, 5.65, 8.77, 7.25, 6.06; 12.71, 11.91, 2.27, 2.60, 4.48, 2.82, 3.65, 3.461, 2.82,all P<0.05). And the personal control, disease correlation and emotional expression; SAS and SDS scores; emotional function and mental health in intervention group were better than those in control group ( t=1.49, 2.74, 2.60, 5.02, 5.18, 5.56, 13.72, all P<0.05). In addition, the medication compliance of patients in both groups was significant improved ( Z=5.56, 13.72, all P<0.01), and the improvement was more marked in the intervention group ( Z=3.22, P<0.01). The study indicates that the comprehensive psychotherapy can more significantly improve the degree of illness perception, negative emotions, quality of life and medication compliance in patients with chronic hepatitis B.

Objective: To explore the clinical effects of split-thickness scalp and allogenic acellular dermal matrix (ADM) in repairing deep wounds of hands in patients with extremely extensive burns. Methods: Six patients with extremely extensive burns complicated by deep burn in hands were admitted to our department from December 2014 to December 2017, including 4 males and 2 females, aged 21 to 58 years. Their total burn areas were from 85% to 95% total body surface area (TBSA), and the sum of deep-partial thickness and full-thickness wounds was larger than 50% TBSA. Under general anesthesia, deep wounds of 10 dorsal hands were repaired by combined transplantation of split-thickness scalp and allogenic ADM in 4 to 6 weeks after injury. The skin grafting range was beyond the metacarpophalangeal joint, including partial dorsal digital deep wounds. Survival of skin grafts on dorsal hands, follow-up of hand shape and functional recovery were observed and recorded. Results: Six patients were successfully treated. There was no infection on the dorsal deep wounds of 10 hands after surgery, and the grafts survived well. During follow-up of 1 to 2 years after operation, there were no recurrent tension blisters or dorsal extension deformity of the metacarpophalangeal joints in 10 hands, the shape and function of hands recovered well, and hand Carroll scores were from 90 to 99 points, with functional levels of Ⅴ and Ⅵ. Conclusions The combined transplantation of split-thickness scalp and allogenic ADM is a good method for repairing deep hand wounds in patients with extremely extensive burns, which can alleviate the cicatrix hyperplasia and contracture of healed hand wounds, and improve the shape and function of hands.

Objective: To investigate the influence of pharmaceutical care pathway on cancer-related fatigue (CRF) and negative emotion in patients with advanced lung cancer undergoing chemotherapy. Methods: Patients with advanced lung cancer admitted to the oncology department of Yongkang first people′s hospital from January 2017 to June 2018 for chemotherapy were randomly divided into two groups:61 cases received conventional clinical pathway management (control group), and 64 cases received conventional clinical pathway combined with pharmaceutical pathway management (intervention group). Fatigue, anxiety, depression scores were compared between the two groups before and after 2, 4 cycles chemotherapy. Results: There was no significant difference in baseline condition between the two groups (P>0.05). After 4 cycles of chemotherapy, emotional, physical and cognitive fatigue scores in the intervention group were lower than control group (t=2.975, 1.512, 2.393, P<0.05). With the increase of chemotherapy cycles, scores of fatigue dimensions in control group were increased (F=44.274,21.740,29.261,7.206, P<0.05). In the intervention group, there were statistically significant differences in scores of fatigue dimensions (F=17.083, 15.902, 17.055, 10.543, P<0.01), among which, scores of behavioral and physical fatigue dimensions were increased (P<0.01), while scores of emotional and cognitive fatigue dimensions were decreased (P<0.01). In terms of negative emotions, depression scores in the intervention group were lower than those in control group at 2 cycles of chemotherapy (t=2.578, P<0.05), and at 4 cycles, anxiety and depression scores were lower than control group (t=7.004, 7.454, P<0.05). As the chemotherapy cycle increased, anxiety and depression scores in the control group increased (F=12.333, 14.819, P<0.05), while those in the intervention group decreased (F=4.992, 3.826, P<0.05). Conclusion The pathway of clinical pharmaceutical care can significantly improve the CRF and negative emotions of patients with advanced lung cancer undergoing chemotherapy.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of miRNA in mouse fibroblasts L929 cell line.Methods L929 cells were cultured in vitro and divided into simulated microgravity (SMG) group and normal gravity (NG) group according to the simple random method.Samples of two groups were collected on 7th day of culture and the total RNAs were extracted,labeled,and hybridized in sequence.Feature Extraction Software was used to collect the array images and get raw data,which were analyzed by Genespring Software.Differentially expressed miRNAs were identified and then validated by qRT-PCR.Target genes of differentially expressed miRNAs were predicted by the databases of Targetscan and microRNAorg,and the intersections of databases were identified as potential regulatory target genes.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were applied to determine the roles of these target genes.Relevant biological functions and/or signaling pathways of the regulated genes especially related with wound healing process were categorized based on their enrichments.Then integration predictions of the miRNA and mRNA expression profiles had been proposed to refine the functional miRNA-mRNA relationships.The miRNA-mRNA functional network and miRNA-mRNA control network were constructed.Results Four miRNA genes were up-regulated significantly including mmumiR-669j,-122-5p,-30a-3p,-6516-3p,among which mmu-miR-669j was up-regulated at 52.84 folds with the greatest significance (P ＜ 0.05).Seventeen miRNA genes were down-regulated significantly including mmu-miR-21a-3p,-miR-28a-5p,-218-5p,-210-3p,-miR-19a-3p,-miR-31-3p,and-miR-19b-3p,among which mmu-miR-28a-5p was down-regulated at 15.47 folds with the greatest significance (P ＜ 0.05).The qRT-PCR showed a high concordance with the microarray results (P ＜ 0.05).Target gene prediction and functional enrichment analysis suggested that a variety of biological processes and signaling pathways involved in wound repair were significantly enriched (P ＜ 0.05).Function network and regulation network of miRNA-mRNA covered all the differentially expressed miRNAs,which suggested that miR-21 a-3p and predicted target gene Smad3 might play an important role in wound healing under microgravity.Conclusions Simulated microgravity by RCCS can significantly affect the expression of stress-related miRNAs in mouse fibroblasts L929.The miRNA target gene prediction and functional enrichment analysis based on gene chip technology may provide theoretical basis for illustrating the mechanism and management of weightlessness stress injury.

Objective: To observe the influence of epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) on peripheral blood T lymphocyte subsets, and its efficacy and safety in the treatment of non-small cell lung cancer (NSCLC) patients.Methods: A total of 35 cases with NSCLC in our hospital were selected as the observation group and 28 healthy persons undergoing health examination at the same time were used as the control group.All the NSCLC patients were with EGFR mutations and accepted the EGFR-TKIs therapy.Flow cytometry was employed to detect T lymphocyte subsets in peripherial blood (including CD3+,CD4+,CD8+,CD4+/CD8+ and NK lymphocy-tes)in one week before the treatment, at the 1st, 2nd and 4th cycle after the EGFR-TKIs treatment, and the curative effect and safety were evaluated as well.Results: Before the chemotherapy, the levels of CD3+, CD4+, CD4+/CD8+ and NK lymphocytes in the NSCLC patients were significantly lower than those in the control group (P<0.01), and CD8+ lymphocytes increased significantly (P<0.01).After the treatment of 1, 2 and 4 cycles, the levels of CD4+and CD4+/CD8+ increased in varying degrees when compared with those before the treatment (P<0.01), and CD8+ decreased significantly when compared with that before the treatment (P<0.01).After the treatment of 2 and 4 cycles, NK cells increased in varying degrees when compared with those before the treatment (P<0.05).After the treatment of 4 cycles, the level of CD3+lymphocytes was significantly higher than that before the treatment (P<0.05).The T lymphocyte immune function in the patients with different therapeutic effects showed statistically significant difference (P<0.05).The order of lymphocyte subgroup improvement was PR>SD>PD.The adverse reactions caused by EGFR-TKIs were slight, and all could be improved markedly after the symptomatic treatment.Conclusion: EGFR-TKIs can significantly regulate the expression of T lymphocyte subsets in NSCLC patients and improve the immune function of the patients with promising safety.