Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To explore the effects of individualized nutrition intervention combined with one-day outpatient mode on blood glucose management and pregnancy outcomes in pregnant women with gestational diabetes mellitus(GDM).Methods A total of 395 pregnant women diagnosed with GDM who underwent prenatal examination in Maternity and Child Health Care of Guangxi Zhuang Autonomous Region from January 2023 to January 2024 were selected as study objects.According to the nutritional intervention measures,the pregnant women were divided into control group(102 cases),nutrition intervention group(141 cases)and combined intervention group(152 cases).The control group was given routine diet education,and nutrition intervention group received individualized nutrition intervention on the basis of control group,and combined intervention group received one-day outpatient intervention on the basis of nutrition intervention group.All pregnant women in three groups were intervened until delivery.The general data,blood glucose indexes and pregnancy outcome of three groups were compared.Results After the intervention,the levels of preprandial blood glucose and 2h postprandial blood glucose on the day of delivery,glycated hemoglobin in late pregnancy and postpartum fasting blood glucose in combined intervention group were significantly lower than those in nutrition intervention group and control group(P＜0.05).The levels of preprandial blood glucose on the day of delivery and postpartum fasting blood glucose in nutrition intervention group were significantly lower than those in control group(P＜0.05).The incidence of preterm birth,low birth weight infants,neonatal hyperbilirubinemia and neonatal hypoglycemia in nutrition intervention group and combined intervention group were significantly lower than those in control group(P＜0.05).Conclusion Individualized nutrition intervention combined with one-day outpatient mode can help to manage blood glucose in pregnant women with GDM and improve pregnancy outcome.

Objective To explore the effects of individualized nutrition intervention combined with one-day outpatient mode on blood glucose management and pregnancy outcomes in pregnant women with gestational diabetes mellitus(GDM).Methods A total of 395 pregnant women diagnosed with GDM who underwent prenatal examination in Maternity and Child Health Care of Guangxi Zhuang Autonomous Region from January 2023 to January 2024 were selected as study objects.According to the nutritional intervention measures,the pregnant women were divided into control group(102 cases),nutrition intervention group(141 cases)and combined intervention group(152 cases).The control group was given routine diet education,and nutrition intervention group received individualized nutrition intervention on the basis of control group,and combined intervention group received one-day outpatient intervention on the basis of nutrition intervention group.All pregnant women in three groups were intervened until delivery.The general data,blood glucose indexes and pregnancy outcome of three groups were compared.Results After the intervention,the levels of preprandial blood glucose and 2h postprandial blood glucose on the day of delivery,glycated hemoglobin in late pregnancy and postpartum fasting blood glucose in combined intervention group were significantly lower than those in nutrition intervention group and control group(P＜0.05).The levels of preprandial blood glucose on the day of delivery and postpartum fasting blood glucose in nutrition intervention group were significantly lower than those in control group(P＜0.05).The incidence of preterm birth,low birth weight infants,neonatal hyperbilirubinemia and neonatal hypoglycemia in nutrition intervention group and combined intervention group were significantly lower than those in control group(P＜0.05).Conclusion Individualized nutrition intervention combined with one-day outpatient mode can help to manage blood glucose in pregnant women with GDM and improve pregnancy outcome.

Objective To observe the changes of laboratory blood indexes in patients with intrahepatic cholestasis of pregnancy(ICP),and analyze the value of blood inflammation indexes and liver function indexes in the diagnosis of ICP and the prediction of delivery mode.Methods A total of 251 patients diagnosed with ICP in this hospital from January 2021 to December 2022 were selected as the ICP group,and another 200 healthy pregnant women were selected as the control group.The patients with ICP were further divided into the severe ICP group(n=47)and the mild ICP group(n=204),the vaginal delivery group(n=113)and the cesarean section group(n=138)according to the severity of ICP and delivery mode.Mann-Whitney U test was used for comparison of parameters between groups,and Spearman method was used for correlation analy-sis.Receiver operating characteristic(ROC)curves were used to evaluate the efficacy of laboratory indicators in diagnosing ICP and predicting delivery mode.Results Neutrophil/lymphocyte ratio(NLR)[6.01(4.45,8.37)vs.3.36(4.12,3.51)]and aspartate transaminase(AST)level[20.00(16.00,33.00)U/L vs.15.00(13.00,18.00)U/L]in the ICP group were significantly higher than those in the control group(P＜0.05),and NLR in the severe ICP group was significantly higher than that in the mild ICP group[4.93(3.87,7.35)vs.4.14(3.12,5.17),P＜0.05].Correlation analysis showed that NLR was positively correlated with AST level(r=0.279,P＜0.001)and ICP severity(r=0.139,P=0.028)in patients with ICP.The area under ROC curve(AUC)of NLR combined with AST for ICP diagnosis was 0.882(95％CI:0.851-0.913).In ad-dition,cholinesterase(CHE)[6 020.00(5 499.50,6 703.50)U/L vs.5 341.50(4 651.75,6 259.25)U/L]and prealbumin(PA)[199.00(177.71,225.20)mg/Lvs.169.17(139.18,204.40)mg/L]levels in the va-ginal delivery group were significantly higher than those in the cesarean section group(P＜0.05),and the AUC of CHE combined with PA for predicting vaginal delivery in ICP patients was 0.727(95％CI:0.664-0.789).Conclusion NLR and AST have potential value in the diagnosis of ICP,and CHE and PA have poten-tial value in predicting delivery mode of ICP patients.

Objective To explore the consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model.Methods Totally 953 patients with solitary breast nodule from multicenter who underwent ultrasound and CEUS were collected.The research team was composed by the initial group (one junior physician from each hospital),check group (one or two physicians who had at least two-year experience of CEUS examination from each hospital),research group (two senior physicians from Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) and cross-blinded group (one or two vice directors or chief physicians from each hospital).At first,the lesions were classified according to the breast imaging reporting and data system (BI RADS) by the initial group and the check group,then new BI RADS classifications were performed by research group and cross blind group with breast CEUS predictive model.The consistency of different physicians in diagnosis of malignant breast lesions was analyzed.Results Among 953 patients,benign lesions were found in 451 patients (451/953,47.32％),malignant lesions were found in 435 patients (435/953,45.65％),and precancerous lesions were found in 67 patients (67/953,7.03％).The accuracy of the initial group,check group,research group and cross-blinded group was 71.67％(683/953),74.92％(714/953),80.17％ (764/953) and 83.42 ％ (795/953),respectively.The consistency of different physicians for diagnosis of malignant breast lesions between initial group and check group was good (Kappa =0.82,P＜0.001),while between initial group and crossblinded group,initial group and research group were both moderate (Kappa =0.56,0.41;all P＜0.001).The consistency of different physicians for diagnosis of malignant breast lesions between cheek group and cross-blinded group,between check group and research group were both moderate (Kappa =0.68,0.51;all P＜0.001).The consistency between research group and cross-blinded group with breast CEUS predictive model was moderate (Kappa =0.74,P＜ 0.001).Conclusion The consistency of different physicians in diagnosis of malignant breast lesions with breast CEUS predictive model was moderate.

Objective To explore the value of contrast-enhanced ultrasonography ( CEUS ) breast predictive model in the optimization of BI-RADS classification of breast lesions . Methods A total of 1049 BI-RADS 4 ,5 breast lesions were obtained from 1039 patients in 8 centers . CEUS examination was performed prior to biopsy or surgery . According to the classification of the model ,class 3 ,4A ,4B and 4C were selected as biopsy thresholds ,and the ROC curve was drawn . The diagnostic sensitivity ,specificity , accuracy ,positive predictive value ,negative predictive value and Jordanian index were calculated for the biopsy threshold . The biopsy rate of breast lesions before and after angiography ,cancer detection rate , follow-up cases of malignant risk were compared . Results There were benign lesions 586 ( 55 .9％ ) , malignant lesions 463 (44 .1％ ) in the 1049 breast lesions . The area of ROC with thresholds of 3 ,4A ,4B and 4C were 0 .695 ,0 .838 ,0 .847 and 0 .757 ,respectively ( all P < 0 .01) . Ultrasonography had a certain diagnostic effect on benign and malignant breast lesions . The diagnostic sensitivity ,specificity ,accuracy , positive predictive value and negative predictive value with class 4A after CEUS set as the biopsy threshold were 93 .32％ ,75 .65％ ,82 .75％ ,75 .57％ and 93 .35％ ,respectively ,and the Jordanian index was 0 .690 . When chass 3 after CEUS was set as the biopsy threshold ,the biopsy rate was reduced from 100％ to 76 .74％ ,the detection rate was increased from 44 .23％ to 56 .77％ ,and the risk of cancer was only 0 .67％ in the follow-up cases . When class 4A was set as the biopsy threshold ,the biopsy rate was reduced from 100％ to 55 .58％ after CEUS . The detection rate of cancer increased from 44 .23％ to 74 .44％ . The risk of cancer was 2 .96％ . Conclusions The biopsy rate of breast lesions in category 4 and 5 would be reduced and cancer detection rate of them would be increased after CEUS ,however ,the risk of malignancy in the follow -up cases would be controlled as low as category 3 and 4A in previous BI-RADS . Thus ,CEUS has a good prospect of in optimizing BI-RADS and reducing biopsy rate in unnecessary lesions .

Objective To investigate the learning curve of contrast-enhanced ultrasonography ( CEUS) in sentinel lymph node( SLN ) of breast cancer and provide a theoretical basis for leaners to learn SLN CEUS . Methods The multi-center study of SLN CEUS in breast cancer" was planned by Sichuan Cancer Hospital . According to the uniform inclusion and exclusion criteria , 511 patients with complete clinical data and follow-up results from 9 hospitals in Multi-center were included in this study . According to the inspection time ,the patients were divided into 3 groups named as group A ( 170 patients) ,group B ( 170 patients) and group C ( 171 patients ) ,respectively . The basic clinical data ,ultrasound imaging data , intraoperative and postoperative pathological findings of all patients were recorded . With the accumulation of cases examined ,analysis was performed to find the learning curve of the SLN CEUS examination time , SLN CEUS detection rate ,SLN CEUS surface marking accuracy rate and SLN CEUS diagnosis rate ,the learning curve was analyzed . Results ① There was no statistical significant difference in patients ages , tumors sizes ,tumors locations ,SLNs numbers and LCs numbers among the three groups( all P > 0 .05) . ②As the number of cases examined increases ,the examination time was reduced gradually ,but SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate were increased gradually( F = 151 .75 , 1 .96 ,7 .49 ,5 .50 ; P = 0 .000 ,0 .143 ,0 .001 ,0 .005 ) . Conclusions The skill of the doctor is improved gradually when learning SLN CEUS . With the number of the cases increase ,the operating time of SLN CEUS is shorted ,and the SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate of SLN-CEUS are gradually increased . It has an important clinical significance for beginners to learn the SLN CEUS technology .

Objective To investigate the effect of pulmonary surfactant on neonatal with acute respiratory distress syndrome.Methods98 cases with neonatal respiratory distress syndrome inthe fourth hospital of Ningbo were randomly divided into experimental group and control group, 49 cases in each group.All patients were given warm, anti infection, and maintain the internal environment stability, prevention of bleeding and other conventional treatment.The control group were treated with mechanical CPAP, the experimental group were given pulmonary surfactant 70mg/kg, concentration is 35mg/mL.Pulmonary surfactant was injected slowly by tracheal intubation at supine, lateral(left, right) and semi recumbent position.The drug was distributed evenly in the lung of the patients who were given the drug 1-2 times.Respiratory frequency (RR), pH, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2) levels and the incidence of complications, clinical effective rate of the tthe two groups were observed and compared.ResultsCompared with pre-treatment, RR and PaCO2 levels were decreased, pH and PaO2 levels were increased after treatment in the two groups, the differences were statistically significant (P<0.05);compared with the control group, RR, PaCO2 level were lower, pH and PaO2 levels were higher in the experimental group, the differences has statistical significance (P<0.05);compared with the control group, the experimental groupwith a low incidence of complications, clinical effective rate is higher, the difference was statistically significant (P<0.05).ConclusionPulmonary surfactant can reduce the respiratory frequency in neonatal with acute respiratory distress syndrome, improve arterial blood gas levels, which get better clinical curative effect.

Objective To provide a comprehensive reference index for different mouse models of herpes simplex virus 1 (HSV-1) infection by investigating the related clinical manifestations, pathological features and characteristics of viral distribution in tissues and organs of BALB/c mice infected with different HSV-1 strains by using different strategies.Methods Acute infection models were established by challenging BALB/c mice at age three or six weeks with HSV-1 17+ and McKrae strains via intranasal and corneal administrations.Correspondingly, chronic infection models were established with BALB/c mice through subcutaneous and foot pad injections.Results Although all experimental mice showed trichiasis and roachback, there were differences in weight and fatality rate among different groups.Results of the quantitative PCR detection indicated that the proliferation of HSV-1 in the nervous tissues (brain, spinal cord, trigeminal ganglion) varied among different groups.The pathological examination indicated that in the acute infection groups, significant pathological changes only occurred in the brain tissues, while in the chronic infection groups, pathological injuries only occurred in the trigeminal ganglia.Although a key index latency-associated transcript (LAT) was not detected in the trigeminal nerve tissues of mice in the chronic infection groups, co-culturing the tissues with Vero cells resulted in infectious lesions in the cells.Conclusion This study indicates that there are significant differences in weight and fatality rate among different BALB/c mouse models of HSV-1 infection.Varied replication dynamics of HSV-1 were observed in different tissues or organs of the BALB/c mice in different groups.Therefore, different indexes should be adopted to evaluate different HSV-1 infection models.