AIM: To investigate the possibility of transfecting siRNA into rabbit cervical cells in transformation zone by the method of solid phase in vivo and to verify the effectivity of siRNA transfection by modifying the permeability of the cervical epithelium. METHODS: A sense strand small-interference RNA (siRNA) for human papillomavirus type 16 (21 bp) was designed and labeled with Cy3. siRNA-Lipo2000-carbomer gum was prepared. Twelve rabbits were included in the study and divided into experimental group and control group. In order to modify the permeability of cervical epithelium, hypertonic saline solution at concentration of 200 mmol/L was used to infuse the cervix in the experimental rabbits for 10 min, and normal saline was used for the control animals. The siRNA-Lipo2000-carbomer gum was applied to the surface of the rabbit cervix. Twenty-four hours later, the rabbits were sacrificed, and the cervix was isolated, cut into 2 parts, one part was for rapid frozen sectioning and the efficiency of transfection was observed under fluorescence microscope, another part was prepared by paraffin embedding and sectioning, and the form of cervical histiocytes was observed. Twelve SCID mice with SiHa cell cervical tumor, divided into experimental group and control group, were also used in the study. The mice in experimental group were treated with siRNA-Lipo2000-carbomer gum for 7 d. The control mice were treated with Lipo2000-carbomer gum only. Five days later, the mice were sacrificed and the tumor was collected, and the HPV16-DNA was measured by PCR. RESULTS: (1) Red fluorescence (Cy3) in cervical epithelium was observed in all rabbits. However, no different effect of siRNA transfection was found between the ways of modifying the cervical epithelium permeability. (2) No abnormal change such as flare, swelling and ulcer at all cervical tissue was observed, the cervical cell form was normal. (3) The titer of HPV16-DNA was decreased significantly after siRNA transfection (P<0.05). CONCLUSION: Transfection of siRNA into rabbit cervical epithelium in vivo is successful by using the method of solid phase and inhibits the processes of HPV-DNA, indicating that using RNAi is a practical way to treat HPV infection in human cercix and to decrease the incidence of cercical carcinoma.

Objective To investigate the clinical efficacy of ilaprazole and bismuth combined ten-day standard quadruple therapy and sequential therapy in the treatment of patients with Helicobacter pylori (H .pylori)infected chronic gastritis.Methods A total of 200 patients with H .pylori-positive chronic gastritis diagnosed by gastroendoscopy examination and rapid urease test (RUT)were randomly divided into standard quadruple therapy group and sequential therapy group,100 cases in each group.One group received ilaprazole,bismuth,amoxicillin-clavulanatepotassium and ofloxacin 10-day standard quadruple therapy, and the other group received ilaprazole, amoxicillin-clavulanatepotassium, ofloxacin and furazolidone 10-day sequential therapy.In four to six weeks after the therapy,the condition of H .pylori eradication was detected by a 14 C-urea breath test.The improvement of clinical symptoms and adverse effects were also observed. Normal distributed and variance homogenized measurement data were compared by t test,while unordered categorical data were analyzed by chi-square test and the exact probability method,and categorical data were compared by two independent sample rank sum test.Results The per-protocol analysis values of H .pylori eradication rates of the standard quadruple therapy group and the sequential therapy group were 88.54%(85/96)and 87.23%(82/94),respectively,while the intention-to-treat analysis values were 85 .00%(85/100)and 82.00%(82/100 ),respectively.The effective rates of symptomatic relief of upper abdominal pain,acid regurgitation,heart burning in the standard quadruple therapy group and the sequential therapy group were 95 .83%(92/96)and 95 .74%(90/94),respectively. The incidence of adverse effects which weve very mild was 6.25 % (6/96 ) and 7.44% (7/94 ), respectively.There was no statistically significant difference in the above three factors between the two groups (all P >0.05).Conclusions Ilaprazole and bismuth combined 10-day standard quadruple therapy and sequential therapy in the treatment of patients with H .pylori positive chronic gastritis both achieves high rates of H .pylori eradication and symptom relief with mild adverse effects.

Objective To investigate the risk factors for acute kidney injury (AKI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI),and to establish a prediction score system for AKI.Methods Totally 296 patients with NSTEMI,who were admitted to the emergency room and further transferred to the Cardiovascular Department in Shantou Central Hospital,were enrolled during January 2011 to April 2014.All patients were divided into AKI group and non-AKI group.Demographics,clinical data and laboratory examinations were collected before and after AKI.AKI risk factors and its OR values were determined after statistically analyzed data by One-Way ANOVA,multivariate logistic regression analysis.Prediction score system for AKI was further established by area under the ROC curve and Hosmer-Lemeshow goodness of fit tests.Results For total 296 patients,the incidence of AKI was 18.4％,including 35 (64.8％) patients in stage Ⅰ,12 (22.2％) patients in stage Ⅱ and 7 (13.0％) patients in stage Ⅲ.Logistic analysis showed that age,heart function (Killip),anemia,the time to emergency department after AMI attack,and absence β-blocker were independent factors associated with AKI.Prediction score system was established which the highest score was 13.A risk score of 3.5 points was determined by Youden' s index,as the optimal cut-off for predict AKI.Patients with ≤3.0 points were considered at low risk,and ≥4.0 points were considered at high risk for AKI.The prediction score system of AKI showed adequate discrimination (area under ROC curve was 0.806) and calibration (Hosmer-Lemeshow statistic test,P =O.503).Conclusions Age,heart function (Killip),anemia,the time to emergency department after AMI attack,and absence β-blocker were independent factors associated with AKI.The clinical prediction score system may help clinicians to make pre-intervention for NSTEMI patients with high AKI risk.

Acute myeloid leukemia (AML) is the most common type of leukemia at present. Although clinical treatment has a certain effect on this disease, most patients still die of relapse or its treatment related diseases. Nowadays, chimeric antigen receptor (CAR) T cells therapy technology has developed rapidly, and has become a hot topic in tumor immunotherapy. The high expression of CD123 in AML cells, low expression or non expression in normal hematopoietic stem cells and tissues, make more and more researchers focus on the technology of CD123+cell immunotherapy. Some studies have confirmed that CD123 CAR-T cells have a certain effect on AML, which provides a new way for clinical treatment of relapsed or refractory AML. This review summarizes the structure, production and delivery methods of CD123 CAR-T cells, and the current research status and shortcomings of CD123 CAR-T cells.

AIM: To explore the expression and significance of receptor tyrosine kinase anexelekto (Axl) in nasopharyngeal carcinoma (NPC).METHODS: Immunohistochemistry was used to detect the Axl protein expression of 78 patients with NPC and 32 patients with nasopharyngeal chronic inflammation (NPI).The correlations between the Axl protein levels and the clinical parameters of NPC patients were analyzed.NPC cells were cultured in vitro, and the expression of Axl in well differentiated CNE1 cells, poorly-differentiated CNE2Z cells and undifferentiated C666-1 cells was detected by immunofluorescence staining.After treatment of the CNE1and C666-1 cells with Axl specific inhibitor TP-0903, CCK-8 assay was used to detect cell viability, flow cytometry was adopted to analyze the cell cycle distribution, qPCR was used to examine the mRNA levels of Axl and proliferating cell nuclear antigen (PCNA), and Western blot was used to examine the protein expression of Axl and p-Axl.RESULTS: Axl protein was localized in the cell membrane and cytoplasm.The rate of high expression of Axl in NPC was significantly higher than that in NPI (P<0.01).High Axl expression showed no correlations with NPC patients'' age, gender and M stage, while positively correlated with the clinical stage, T stage and N stage (P<0.05).Axl protein showed a low level in the CNE1 cells, but showed a high level in CNE2Z and C666-1 cells.TP-0903 inhibited cell viability in concentration and time dependent manners.TP-0903 at 2 nmol/L showed significant inhibitory effects, as evidenced by arresting the cell cycle at G0 phase and reducing Axl activity and PCNA expression.CONCLUSION: High expression of Axl promotes the clinical progress of NPC.TP-0903 significantly inhibits the viability of NPC cells, suggesting that Axl may be a valuable target in the NPC treatment.

OBJECTIVETo investigate the effects of Sanren decoction on the immune function of rats with spleen-stomach damp-heat (DHSS) syndrome.

METHODSFifty male SD rats were randomly allocated into normal control group, DHSS model group, and 3 Sanren decoction groups (high, medium and low doses). The effects of the decoction on the body mass, rectal temperature (RT), water and food intake, histopathological changes of the gastrointestinal mucosa and serum levels of interleukin (IL)-4 and interferon (IFN)-γ were evaluated.

RESULTSThe serum levels of IFN-γ and IL-4 in the model group significantly increased compared with those in the control group (P<0.01), with a slightly increased IFN-γ/IL-4 ratio (P>0.05). Sanren decoction obviously reduced the rectal temperature and significantly decreased the production of both cytokines. High-dose Sanren decoction caused more markedly decreased IL-4 level (P<0.05) to result in a significantly increased IFN-γ/IL-4 ratio (P<0.05).

CONCLUSIONSA shift of Th1/Th2 balance toward Th1 immune response is demonstrated in rats with DHSS syndrome, and Sanren decoction produces a protective effect on the gastrointestinal mucosa by immunoregulation.

Animals ; Diagnosis, Differential ; Digestive System Diseases ; drug therapy ; immunology ; Inflammation ; drug therapy ; immunology ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Syndrome ; Th1-Th2 Balance ; drug effects

Objective To study the mechanism of urinary Kallidinogenase combined with aspirin in treat-ment of acute cerebral infarction. Methods Eighty-six patients with acute cerebral infarction were randomly divid-ed into the observation group(n=43)and the control group(n=43).The observation group was treated with uri-nary Kallidinogenase combined with aspirin,while the control group was treated only with aspirin.Two weeks after the treatment,variables of hemorheology,serum Hcy,hs-CRP,VEGF,IL-6,Cys-C,neurological deficit(NI-HSS)and daily living ability(ADL)were compared between the two groups. Results After treatment,the serum Hcy,hs-CRP,VEGF,Cys-C,IL-6 levels,the NIHSS and ADL in the observation group were significantly better improved than those of the control group(P<0.05).The clinical efficacy in the observation group was significantly higher than that of the control group[95.35%(41/43)vs 74.42%(32/43)](P<0.05).Conclusion Urinary Kal-lidinogenase combined with aspirin is more effective in the treatment of acute cerebral infarction. The mechanism may be related to the early improvements of serum Hcy,hs-CRP,VEGF,Cys-C and IL-6 expression.

Objective:A machine learning algorithm was used to develop a predictive model of self-injury among college students and to explore the high-risk factors for self-injury among college students.Methods:From November to December 2022, a convenience sample of 791 college students from a university in Hebei Province was selected.Whether the self-injurious behavior occurred or not was regarded as an outcome variable.The basic demographics data were collected for statistical analysis.The adolescent self-harm questionnaire, the acquired helplessness scale, the Chinese version of the interpersonal needs questionnaire, the adolescent life events scale, and the childhood traumatic experiences questionnaire were used for assessment.The predictor variables were statistically analyzed by SPSS 26.0 software, and the performance of the model was evaluated by random forest, support vector machine and logistic regression so as to predict the self-injury behavior of college students.The model performance was evaluated by the accuracy, F1 score, sensitivity, specificity, and AUC value of the model, and the optimal model was selected.Finally, the optimal model was used to analyze the high-risk factors of college students' self-injury behaviors.Results:(1) The results of one-way ANOVA showed that the detection rate of self-injury behavior among college students was 42.4%(335/791), and the detection rate of male students was significantly higher than that of female students ( χ2=14.139, P<0.05). Individuals with lower-middle monthly household income(RMB 3 000-5 999) had a significantly higher detection rate of self-injury behavior than those with other monthly household income( P<0.05). (2) The accuracy of random forest, support vector machine, and logistic regression models were 85.53%, 85.96%, and 68.86%, F1 scores were 0.853, 0.864, and 0.676, and sensitivities were 83.91%, 89.04%, and 64.91%, respectively.The AUCs of support vector machine, logistic regression models and random forest were 0.89, 0.73 and 0.92.(3) The top ten characteristic variables of high risk factors for college students' self-injury behaviors based on the random forest algorithm with better predictive efficacy were emotional abuse, frustration of belonging, helplessness, interpersonal relationship factor, despair, emotional neglect, academic stress factor, monthly family income, perception of tiredness, and health adaptation factor, in that order. Conclusions:Random forest is optimal for predicting self-injury behavior among college students compared to support vector machine and logistic regression.Factors influencing self-injury behavior among college students originate from environmental factors, individual factors and interpersonal factors.

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury, but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes (CMs) for driving the differentiation of cardiac stem cells (CSCs). Forced hypoxia-inducible factor 1 (HIF-1) expression and physical hypoxia (5% O) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1 by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor (PD98059), but not inhibitors of JNK (SP600125), Notch (DAPT), NF-B (PTDC), JAK (AG490), or STAT3 (Stattic) suppressed hypoxia-induced Jagged1 protein expression in CMs. c-Kit CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed GATA4, SM22 or vWF, but not Nkx2.5 and cTnI. Moreover, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU/Nkx2.5 cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced differentiation. Our results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling, and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures HIF-1/Jagged1/Notch signaling.