Objective To assess the clinical utility of single-molecule real-time technology(SMRT)in identifying triplicated α-globin genes and compound variant alleles.Methods A total of 36 samples with tripli-cated α-globin genes were collected.Among them,28 samples were confirmed by PCR flow-through hybridiza-tion and 8 samples were confirmed by Next Generation Sequencing(NGS).These 36 samples included tripli-cated α-globin genes compound variants with cis or trans arrangements unknown,such as αααanti4 2 compoundαcsα(2 cases),αααanti4.2 compound-α3.7(10 cases),and HKαα/--SEA pending confirmation(2 cases),SMRT technology was employed to detect thalassemia gene variants.Additionally,a pedigree with the genotype ofαααanti4.2 compound-α3.7 variant was recruited,including the proband(Ⅱ-1),its father(Ⅰ-1),and mother(Ⅰ-2).PCR flow-through hybridization and SMRT were employed to detect thalassemia gene variants.Results SMRT detected 35 out of 36 samples with triplicated α-globin genes,and 1 sample with quadrupllcated α-globin genes(ααααanti4.2).Among the 2 αααanti4 2 compound αCSα variant samples,both αααanti42 and αCSα were arranged in trans,with a genotype of αααanti4.2/αCSα.Among the 10 αααanti4.2 compound-α3.7 variant samples,9 samples hadαααanti4.2 and-α3.7 in a cis arrangement,with a genotype of HKαα/αα,and 1 sample had αααannti4.2 and-α3.7 in a trans arrangement,with a genotype of αααanti4.2/-α3.7.Compared with PCR flow-through hybridization,SMRT detected one case of a large segment deletion in the β-globin gene and two unknown variants,which led to an increase in the positive detection rate of approximately 10.71％(3/28).The pedigree analysis showed that the proband(Ⅱ-1)inherited αααanti4.2 and-α3.7 variants from his mother(Ⅰ-2),with a genotype of HKαα/αα,con-sistent with the SMRT detection results.Conclusion SMRT can accurately detect triplicated or quadrupllcat-ed α-globin genes,and compound variant alleles.It offers high accuracy,enables one-step identification of cis or trans arrangements,and provides comprehensive coverage of thalassemia gene variations,demonstrating its significant clinical value.

OBJECTIVE To explore the short-term and long-term efficacy of bevacizumab combined with paclitaxel （PTX） and carboplatin （CBP） chemotherapy in the treatment of persistent or recurrent cervical cancer， as well as its impact on patient quality of life， tumor markers and safety. METHODS Totally 80 patients with persistent or recurrent cervical cancer admitted to our hospital from January 2020 to October 2022 were randomly divided into control group （40 cases） and observation group （40 cases） using a random number table method. Both groups received PTX+CBP chemotherapy， while the observation group was treated with bevacizumab in combination. Both groups were treated continuously for 6 cycles. The recent efficacy， the incidence of toxic side effects as well as European Organization for Research and Treatment of Cancer Life Questionnaire Core 30 （EORTC QLQ-C30） scores， and the serum tumor markers [carcinoembryonic antigen （CEA）， carbohydrate antigen 125 （CA125）， and squamous cell carcinoma antigen （SCCA）] levels before and at the end of the entire course of treatment were compared between two groups. The survival curves of the two groups were drawn by using Kaplan-Meier method， and progression-free survival （PFS） and overall survival （OS） were compared between the two groups by Log-rank test. RESULTS The objective response rate of the observation group was significantly higher than that of the control group （62.50% vs. 35.00%， P＜0.05）， and the median PFS （9.30 months vs. 6.30 months） and median OS （14.90 months vs. 10.60 months） were also significantly longer than the control group （P＜0.05）. EORTC QLQ-C30 score of the observation group after treatment was significantly higher than that of the control group （P＜0.05）. Compared to before treatment， the serum levels of CEA， CA125 and SCCA in both groups were significantly reduced after treatment （P＜0.05）， while the observation group had a larger decrease （P＜0.05）. There was no significant difference in the grading of various types of toxic side effects between the two groups during treatment （P＞0.05）. Most patients experienced automatic disappearance of toxic side effects 1-2 months after discontinuation of medication， or symptoms disappearance after symptomatic treatment. CONCLUSIONS The combination of bevacizumab and PTX+CBP chemotherapy regimen can effectively improve the objective efficacy rate of persistent or recurrent cervical cancer， reduce serum tumor marker levels， improve patient quality of life， prolong survival， and have good safety.

Objective To explore the relationships of ultrasound vascular index quantification and elastic modulus with biological characteristics of breast cancer and its clinical significance. Methods A total of 103 patients with breast cancer who received neoadjuvant chemotherapy (NAC) were selected as study subjects. The relationships of the quantification of vascular index (VI) and maximum elastic modulus (E_max) of shear wave elastography (SWE) with the biological characteristics of breast cancer before NAC were analyzed. According to the pathological response of NAC, the patients were divided into significant response group and non-significant response group. The change rates of VI and E_max at the end of different cycles of NAC were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the change rates of VI and E_max at the end of different cycles to predict the pathological response of NAC in breast cancer. Results Before NAC, VI and E_max were related to the degree of differentiation, pathological stage and HER-2 expression in breast cancer tissues (P < 0.05). The significant response group had higher change rates of VI and E_max at the end of 1, 2, and 4 week of NAC compared to the non-significant response group (P < 0.01). At the end of the second cycle, AUC of change rates of VI combined with E_max predicted the pathological response of NAC in breast cancer was 0.918, with the sensitivity of 0.874, and specificity of 0.905, which were higher than 0.832 of AUC, 0.78 of sensitivity, and 0.827 of specificity at the end of 1 week of NAC, and were higher than 0.853 of AUC, 0.827 of sensitivity, and 0.849 of specificity at the end of the fourth week. Conclusion VI and E_max are correlated with the degree of differentiation, pathological stage and HER-2 expression in breast cancer. At the end of the second cycle of chemotherapy, the change rates of the VI combined with E_max have the best efficacy in predicting the pathological reaction of NAC in breast cancer.

Background/Aims: In patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), the optimal timing of endoscopy is still a matter of dispute. We conducted a systematic review and meta-analysis to determine the clinical benefit of early endoscopy. Methods: A literature search of the MEDLINE, Embase, and Cochrane databases was conducted to identify publications from inception to March 1, 2022. Eligible studies included observational cohort studies and randomized controlled trials that reported clinical outcomes of endoscopy in patients with ANVUGIB. ANVUGIB patients who underwent endoscopy within 24 hours of admission were considered to have had an early endoscopy. The primary outcome was the mortality rate in ANVUGIB patients who had early or nonearly endoscopy. Results: The final analysis included five randomized controlled studies (RCTs) and 20 observational studies from the 1,206 identified articles. The mortality rate was not significantly reduced among patients who received endoscopy performed within 24 hours, whether in cohort studies nor in RCTs. For subgroup analysis, a higher mortality rate was found only among patients who received very early endoscopy within 12 hours (odds ratio, 1.66; p<0.001, I 2 =0) in cohort studies. No significant difference in mortality rates was found among patients at high risk of bleeding who received early versus nonearly endoscopy. Conclusions Early endoscopy within 24 hours does not appear to significantly reduce the mortality rates of patients with ANVUGIB. Further well-designed studies are warranted to address if very early endoscopy within 12 hours can provide a clinical benefit for patients at high risk of bleeding.

Objective:To establish neurodevelopmental mice model of schizophrenia(SZ) with prepulse inhibition(PPI) deficits and investigate the effectiveness of olanzapine on PPI disruption.Methods:On the 9th day of pregnancy of SPF grade C57BL/6 mice, female mice were injected with polyinosinic acid poly (I∶C) (6 mg/kg) through tail vein for immune stimulation. The stress model was constructed by chronic unpredictable mild stress 30-40 d after birth (PND30-40). The offspring mice were divided into pregnancy immune stimulation + adolescent stress group (P + S + group), pregnancy immune stimulation group (P + S- group), adolescent stress group (P-S+ group) and non stimulation group (P-S-group), with 18 mice in each group. The mice in P+ S+ group were divided into OLZ intervention group (OLZ group) and non-OLZ intervention group (non-OLZ group), with 9 mice in each group. The PPI function of mice was detected by acoustic startle reflex test after modeling and OLZ intervention. Adopt StatView Version 5.0 software for data analysis, and multi factors analysis of variance was used to test the main effect, interactive effect and simple effect of each factor.Results:The main effects of maternal Poly(I: C) immune activation and pubertal chronic unpredictable stress were significant( F(1, 330)=47.72, P<0.01), and there was a significant interaction between the two factors( F(1, 330)=14.80, P<0.01), simple effect analysis showed that average percent prepulse inhibition (PPI%) in P+ S+ group((15.42±6.13)%) was significantly decreased compared with groups of P+ S-((27.33±4.58)%), P-S+ ((31.17±3.97)%) and P-S-((47.14±12.28)%)(all P<0.01). There was significant gender difference in Prepulse inhibition(PPI)score( F(1, 396)=61.94, P<0.01), in male and female mice, average startle reactivity of Pulse under Prepulse+ Pulse influence of distinct intensities was significantly different( F(1, 198)=18.68, 18.44, P<0.01), and the maternal Poly(I∶C) immune activation had a significant main effect( F(1, 198)=32.18, 12.58, P<0.01) and interaction with pubertal chronic unpredictable stress( F(1, 198)=34.54, 11.39, P<0.01), simple effect analysis suggested that the average startle reactivity of Prepulse+ Pulse in P+ S+ group(0.47±0.12) was significantly higher than other three groups(P+ S-: 0.36±0.11, P-S+ : (0.25±0.22), P-S-: (0.31±0.19)) in male mice( P<0.01) and in P-S+ group was significantly higher than the other three groups in female mice ( P<0.01). OLZ treatment could efficiently reverse the deficits on PPI by increasing PPI%( F(1, 165)=18.24, P<0.01), OLZ could reduce PPI score in male "dual-hit" model mice( F(1, 102)=21.81, P<0.01)and raise it in female( F(1, 102)=4.88, P<0.05). Conclusion:OLZ can reverse PPI deficits in schizophrenic neurodevelopmental model mice, and in the evaluation of PPI function in the model mice through PPI of acoustic startle reflex, PPI% has better stability and reactivity to OLZ intervention.

Objective:To investigate the relationship between the changes of default network topology properties of brain function and cognitive function in patients with end-stage renal disease (ESRD).Methods:A total of 31 patients with ESRD were enrolled in the Department of Nephrology, Changzhou Second Hospital Affiliated to Nanjing Medical University from January 2019 to December 2020, and 18 healthy persons were included in the same period as the control group.The cognitive function was evaluated with the Montreal cognitive assessment (MoCA) and trail making tests, and then the subjects were examined by resting-state functional magnetic resonance imaging (rs-fMRI). After preprocessing, the brain functional network was constructed and the topology properities of the network were calculated.The SPSS 20.0 software was used for statistical analysis.Independent sample t-test, chi square test and Pearson correlation analysis were used for data statistics. Results:(1) The score of MoCA in the ESRD group(23.37±1.77) was significantly lower than that in the healthy control group(27.94±1.13)( t=9.537, P<0.001). (2) The levels of Eglobal, Elocal, Cp and Sigma in ESRD group ((0.129±0.025), (0.148±0.040), (0.188±0.046), (1.593±0.650)) were significantly lower than those in healthy control group ((0.160±0.040), (0.212±0.024), (0.276±0.049), (2.004±0.864))( t=3.591, 7.474, 7.058, 2.034, all P<0.05). The Lp value of the ESRD group (8.131±1.905) was significantly higher than that of the control group (6.777±2.150)( t=2.583, P< 0.05). The node efficiency values of bilateral dorsolateral superior frontal gyrus, left middle frontal gyrus, bilateral posterior cingulate gyrus, right hippocampus, left superior marginal gyrus, bilateral angular gyrus and bilateral cuneate anterior lobe in ESRD group ((0.133±0.071), (0.201±0.047), (0.211±0.106), (0.175±0.066), (0.276±0.113), (0.122±0.146), (0.042±0.075), (0.171±0.027), (0.154±0.078), (0.240±0.095), (0.161±0.056))were lower than those in the healthy control group((0.312±0.075), (0.289±0.091), (0.277±0.132), (0.284±0.053), (0.368±0.063), (0.231±0.227), (0.120±0.162), (0.296±0.064), (0.310±0.186), (0.318±0.066), (0.286±0.103))( t=2.107-9.436, all P<0.05). (3)Pearson correlation analysis showed that the node efficiency values of bilateral posterior cingulate gyrus and right hippocampus in ESRD group were positively correlated with the score of MoCA( r=0.36, 0.49, 0.53, all P<0.05). Conclusion:The topological structure of brain functional network is abnormal in ESRD patients, which can affect the cognitive function of patients.

Objective: To analyze the clinical characteristics and treatment experience of Vitamin B12 (VB12) deficient patients with recurrent aphthous ulcers (RAU) to improve the clinical efficacy. Methods: A retrospective analysis was performed on 15 cases of recurrent oral ulcers from January 2016 to September 2018. The causes were analyzed according to the patients’ clinical characteristics. Results: In total, 15 patients with RAU had no remission after routine immunotherapy. Further clinical examination suggested that vitamin B12 levels were reduced. The erythrocyte mean corpuscular volume (MCV) was significantly increased, and the average number of red blood cells (RBC) and hemoglobin (Hb) levels were decreased. RAU disappeared after vitamin B12 supplementation. Routine blood work showed that the MCV returned to the normal range, which was statistically significant compared with the pretreatment MCV (P < 0.001). Vitamin B12 serum levels were significantly higher (P < 0.001) than those before treatment. Conclusion When the main manifestation of vitamin B12 deficiency is recurrent oral ulcer symptoms, dentists should examine the lesions carefully, inquire about the medical history in detail, and perform further serological tests when necessary to avoid the overuse of immunosuppressive drugs for treatment.

Objective To investigate the differential expression of microRNA (miRNA) in schizophrenia (SZ) patients,and explore the comorbidity of SZ and depression disorder based upon miRNA expression.Methods Affymetrix array analysis was used to investigate the differentially expressed miRNA in SZ patients firstly,and then quantitative real-time polymerase chain reaction (qRT-PCR) was further carried out to confirm the selected miRNA in peripheral blood mononuclear cells of 40 SZ patients,whom were administered by Positive and Negative Syndrome Scale (PANSS) and the selected miRNAs in depression disorder patients has also been confirmed by Affymetrix array analysis and qRT-PCR in our previous studies.Results Affymetrix array analysis indicated that there existed 33 miRNAs which differentially expressed (32 up-regulated and 1 down-regulated) compared with normal controls.qRT-PCR results suggested that the expression of 8 miRNAs (miR-1273d,miR-1303,miR-3064-5p,miR3131,miR-3687,miR-4428,miR-4725-3p and miR-5096) were significantly up-regulated in SZ;the miRNA differentially expressed in depression disorder patients also had differential expression in SZ patients (P＜0.05).There were significant correlation between the miRNAs differentially expressed in depression disorder patients and in SZ patients (P＜0.01).MiR-1972 differentially expressed in depression disorder patients had significant positive correlation with the positive symptoms of PANSS (P＜0.05),and miR-26b was positively correlated with composite factor (P＜0.05).Conclusion Comorbidity of SZ and depression disorder is observed not only on the clinical symptoms,but on the molecular genetic basis.

Objective To summarize the nursing cooperation during anterior cruciate ligament(ACL)reconstruction with autogenous quadurpled hamstring tendons under arthroscopic guide.Method Data of 25 cases of ACL reconstruction with autogenous quadrupled hamstring tendons under arthroscopic guide during January 2008 and December 2012 were analyzed and summarized the key points retrospectively.Result All the cases of ACL reconstruction were completed smoothly without any complication.Conclusion Excellent nursing cooperation including well-done preoperative preparation of instruments and accurate surgical cooperation are a guarantee of successful operation.