Objective:To study the efficacy of norepinephrine in the treatment of neonates with septic shock.Methods:A prospective observation study of neonates with septic shock, who received norepinephrine in the neonatal intensive care unit of Guangdong Women and Children's Hospital from January 2019 to November 2020. All infants had functional echocardiography for hemodynamic monitoring before norepinephrine treatment and 1 hour thereafter blood pressure, heart rate, arterial blood gas analyses were recorded at the same time. The intravenous fluid volume and urine volume from the diagnosis of shock to the commencement of norepinephrine therapy (T0) and 24 hours thereafter (T1) were recorded, and the hemodynamic parameters, vasoactive drugs and clinical outcomes were analyzed.Results:A total of 66 newborns were enrolled, including 27 cases of mild shock, 33 cases of moderate shock and 6 cases of severe shock. 48 were male infants, 38 cases were premature infants. The gestational age was (35.2±4.1) weeks and the birth weight was (2 476±909) g. The median time of shock diagnosis was 2 days after birth, and the median shock score was 4 points. The median time from the diagnosis of shock to the start of norepinephrine treatment was 7.5 hours. Compared with that before norepinephrine treatment, stroke volume, stroke volume index, cardiac output, cardiac index, left ventricular ejection fraction, shortening fraction, systolic blood pressure, diastolic blood pressure, mean arterial pressure, blood pH and BE at 1 hour after treatment were increased, heart rate and blood lactic acid were decreased, the differences were statistically significant ( P<0.05). Urine volume was increased 24 hours after treatment ( P<0.05), and fluid overload decreased ( P<0.05). The maximum dopamine dose, the down-regulation time and duration of vasoactive drugs were positively correlated with the time to start norepinephrine therapy ( r=0.325、 r=0.383、 r=0.319, P<0.05). Among the 66 infants, 58 infants with shock had been corrected and 14 infants died within 28 days. Conclusions:Norepinephrine is effective and feasible in the treatment of neonatal septic shock and can significantly improve hemodynamic parameters.

Objective:To study the clinical value of neonatal shock score (NSS) and septic shock score (SSS) in the evaluation of mortality and serious complications of neonatal refractory septic shock.Method:From January 2019 to November 2020, clinical data of neonates with septic shock admitted to Neonatal Department of our hospital were retrospectively reviewed. According to the final outcomes, neonates were assigned into good prognosis group (neonates survived without serious complications) and poor prognosis group (neonates were dead within 28 days after birth and/or had serious complications). The NSS and SSS were calculated according to the worst value of each index during the septic shock course. SSS included computed septic shock score (cSSS) and bedside septic shock score (bSSS). The receiver operating characteristic (ROC) curve was used to analyze the efficacy of each scoring system evaluating the risk of poor prognosis due to septic shock. The correlation of each scoring system with the duration of vasoactive drugs was analyzed using Spearman rank correlation analysis.Result:A total of 72 neonates were enrolled, including 45 in good prognosis group and 27 in poor prognosis group. The vasoactive drug score, serum lactate level, NSS and cSSS in poor prognosis group were significantly higher than good prognosis group ( P<0.05).And bSSS score showed no significant differences between the two groups ( P>0.05). The area under the ROC curve (AUC) of NSS and cSSS predicting the adverse prognosis of neonates with septic shock were 0.644 (95% CI 0.510~0.777, P<0.05) and 0.765 (95% CI 0.654~0.877, P<0.05). The best cut-off values for NSS and cSSS predicting poor prognosis were 4.0 and 80.5, respectively. The positive predictive value (PPV) (81.3% vs. 47.5%) and negative predictive value (NPV) (75.0% vs. 70.6%) of cSSS were higher than NSS. Spearman rank correlation analysis showed that cSSS was positively correlated with the duration of vasoactive drugs( r=0.487, P<0.01). Conclusion:Both shock scoring systems have an evaluation value for the prognosis of neonatal septic shock. The evaluation value of cSSS is better than NSS, and can be used as a main tool for the evaluation of neonatal refractory septic shock.

Objective:To study the predictive value of vasoactive-inotropic score (VIS), shock score and lactate level for the outcome of term infants with septic shock.Methods:From January 2019 to October 2020, clinical data of term infants with septic shock admitted to our department were reviewed. According to their clinical outcome, the infants were assigned into the survival group and the deceased group and the differences of the two groups were compared. Logistic regression was used to determine the risk factors of mortality in term infants with septic shock. Receiver operating characteristic curve was used to compare the predictive efficacy of VIS, shock score and lactate level for the outcome of septic shock.Results:Significant differences existed between the survival group and the deceased group in the following: maximum VIS, maximum shock score, maximum lactate level, the mean value of VIS during the second 24 h, the mean value of lactate during the first and second 24 h ( P < 0.05). Meanwhile, maximum VIS ( OR = 1.038, 95% CI 1.014~1.063), maximum shock score ( OR = 2.372, 95% CI 1.126~4.999) and the mean value of lactate during the first 24h ( OR = 2.983, 95% CI 1.132~7.862) were correlated with mortality in the infants ( P < 0.05). The area under the curve of maximum VIS was the most prominent, with 58.5 as cut-off. Conclusions:Among the three indicators, VIS has the best predictive value for mortality outcome in term infants with septic shock, followed by shock score and lactate level.

Objective:To study the threshold of fluid overload (FO) and its risk factors in neonatal septic shock.Methods:From January 2019 to November 2020, clinical data of infants with septic shock hospitalized in the neonatal department of our hospital were reviewed. With poor prognosis as the outcome, ROC curve was drawn based on 24 h (from the beginning of septic shock), 48 h and 72 h FO value. FO cutoff value was determined as area under curve (AUC) reached maximum. Risk factors of FO were analyzed between FO

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Objective: To investigate the effect of irradiation to anastomosis from preoperative radiotherapy for patients with rectal cancer by studying the pathological changes. Methods: In this retrospective study, patients enrolled in the FOWARC study from January 2011 to July 2014 in the Sixth Affiliated Hospital of Sun Yat-Sen University were included. In the FOWARC study, enrolled patients with local advanced rectal cancer were randomly assigned to receive either neoadjuvant chemo-radiotherapy or chemotherapy. Among these patients, 23 patients were selected as radiation proctitis (RP)group, who fulfilled these conditions: (1) received neoadjuvant chemo-radiotherapy followed by sphincter-preserving surgery; (2) developed radiation proctitis as confirmed by preoperative imaging diagnosis; (3) had intact clinical samples of surgical margins. Twenty-three patients who had received neoadjuvant chemo-radiotherapy but without development of radiation proctitis were selected as non-radiation proctitis (nRP) group. Meanwhile, 23 patients received neoadjuvant chemotherapy only were selected as neoadjuvant chemotherapy (CT) group. Both nRP and CT cases were selected by ensuring the basic characteristics such as sex, age, tumor site, lengths of proximal margin and distal margin all maximally matched to the RP group. Both proximal and distal margins were collected for further analysis for all selected cases. Microscopy slices were prepared for hematoxylin & eosin staining and Masson staining to show general pathological changes, and also for immunohistochemistry with anti-CD-34 as primary antibody to reveal the microvessel. Microvessel counting in submucosal layer and proportion of macrovessel with stenosis were used to evaluate the blood supply of the proximal and distal end of anastomosis. A modified semi-quantitative grading approach was used to evaluate the severity of radiation-induced injury. Either ANOVA analysis, Kruskal-Wallis rank-sum test or χ² test was used for comparison among three groups, and Mann-Whitney U test was used for comparison between two groups. Results: Compared to group of neoadjuvant chemotherapy only, patients receiving neoadjuvant chemo-radiotherapy had lower microvessel count in both proximal and distal margins (M(Q_R): proximal, 25.5 (19.6) vs. 50.0 (25.0), Z=3.915, P=0.000; distal, 20.5 (17.5) vs. 49.0 (28.0), Z=3.558, P=0.000), higher proportions of macrovessel with stenosis (proximal, 9.5% (23.8%) vs. 0, Z=3.993, P=0.000; distal, 11.5%(37.3%) vs. 0 (2.0%), Z=2.893, P=0.004), higher histopathologic score (proximal, 4.0 (2.0) vs. 1.0 (2.0), Z=6.123, P=0.000; distal, 5.0 (3.0) vs. 2.0 (1.0), Z=4.849, P=0.000). In patients receiving neoadjuvant chemo-radiotherapy, compared to nRP group, RP group had lower microvessel count in both proximal and distal margins (proximal, 19.0 (23.0) vs. 30.4 (38.0), Z=2.845, P=0.004; distal, 19.0 (13.0) vs. 30.0(29.1), Z=2.022, P=0.043), higher proportions of macrovessel with stenosis (proximal, 23.0% (40.0%) vs. 0(11.0%), Z=3.248, P=0.001; distal, 27.0% (45.0%) vs. 3.0% (19.0%), Z=2.164, P=0.030). Rate of anastomotic leakage for CT, nRP and RP group were 8.7% (2/23), 30.4% (7/23), and 52.2% (12/23), and the differences among three groups were statistically significant (χ²=10.268, P=0.007). Conclusion Radiation-induced injury existed on both margins of the resected rectal site after preoperative radiotherapy, and those diagnosed as radiation proctitis had more severe microvascular injury.

Objective To investigate the"Precision Treatment for Oncology"course,which is offered by Peking Union Medical College.The course is aiming for collecting students'opinions and suggestions to optimize the course setting and improve the teaching quality.Methods This investigation collected data by questionnaire survey and in-terviewing from Dec.2021 to Feb.2022.The questionnaire data and interview data were analysed.Results Thirty-six quantitative questionnaires and five qualitative questionnaires were included.Improving professional knowledge and personal interests were two main reasons for students to choose courses,which existed statistical differences on different aspects of course evaluation.The overall score evaluated by medical students was 9.22 and 94.4%of the students thought the course achieved the desired goal.The scores of teachers'teaching attitude,frontier and practi-cality of course content were 9.81,9.08 and 8.86 points respectively.The students hoped to increase the case analysis practice and thematic discussion activities to enrich the teaching form.Conclusions This elective course for graduate is recognized and accepted by students.More efforts are needed in future to optimize curriculum set-tings,innovate teaching methods,improve teaching quality and explore new pathways for medical graduate educa-tion matching the needs of students.

Objective:To explore the effect of quality improvement of hemodynamic monitoring on fluid overload (FO) and outcome in newborns with septic shock.Methods:Non-invasive cardiac output monitoring and functional cardiac ultrasound quality improvement program was started during January 2020 in our hospital. Neonates with septic shock admitted before and after the program were retrospectively analyzed. From January 2018 to December 2019 was pre-improvement period when fluid resuscitation was routinely performed and vasoactive drugs was selected empirically. From January 2020 to December 2021 was post-improvement period when fluid resuscitation and/or use and adjustment of vasoactive drugs were guided by hemodynamic parameters. The 24 h, 48 h, 72 h FO, duration of invasive respiratory support, vasoactive-inotropic score, septic shock score, incidences of complications and all-cause mortality were compared between the two groups.Results:A total of 284 eligible cases were enrolled, including 136 cases in pre-improvement group and 148 cases in post-improvement group. Post-improvement group had significantly lower gestational age (GA), birth weight (BW) and body weight at disease onset than pre-improvement group ( P<0.05). Incidences of 48 h and 72 h FO, fluid resuscitation volume within 72 h, pulmonary hemorrhage and periventricular leukomalacia (PVL) were significantly lower in the post-improvement group ( P<0.05). No significant differences existed in 24 h FO, other complications and all-cause mortality between the two groups ( P>0.05). No significant differences existed in GA and BW for neonates with pulmonary hemorrhage and PVL between the two groups ( P>0.05). Conclusions:Quality improvement of hemodynamic monitoring can effectively improve FO and reduce the incidences of pulmonary hemorrhage and PVL.

Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

BACKGROUND:Increased homocysteine level induces apoptosis of human umbilical vein endothelial cells,but the mechanism remains unclear. OBJECTIVE:To investigate the role of hsa-circ-0001360 in human umbilical vein endothelial cell apoptosis induced by homocysteine. METHODS:In vitro cultured human umbilical vein endothelial cells were divided into control group,homocysteine group,interference control group,interference control + homocysteine group,hsa-circ-0001360 interference group,hsa-circ-0001360 + homocysteine interference group,overexpression control group,overexpression control + homocysteine group,hsa-circ-0001360 overexpression group and hsa-circ-0001360 + homocysteine overexpression group.All groups were treated with 100 μmol/L homocysteine.After 72 hours of intervention,the expressions of apoptosis-related proteins Bax,Bcl-2,and Caspase-3 were detected by western blot assay.The apoptotic rate was detected by flow cytometry.Quantitative real-time PCR was used to detect the expression of hsa-circ-0001360. RESULTS AND CONCLUSION:(1)Compared with the control group,the expression of Caspase-3 and Bax was significantly increased(P<0.01),and the expression of Bcl-2 was significantly decreased(P<0.01),and the apoptotic rate was significantly increased(P<0.01)in the homocysteine group.(2)Compared with control group,the expression of hsa-circ-0001360 was significantly increased in the homocysteine group(P<0.01).(3)The expression of hsa-circ-0001360 was significantly higher in the cytoplasm than that in the nucleus(P<0.01).(4)Compared with the interference control C group and interference control + homocysteine group,the expressions of Caspase-3 and Bax were significantly decreased(P<0.01),while the expression of Bcl-2 was significantly increased(P<0.01);the apoptotic rate was significantly decreased(P<0.01)in sh-hsa-circ-0001360 interference group and sh-hsa-circ-0001360 + homocysteine interference group.(5)Compared with overexpression control group and overexpression control + homocysteine group,the expressions of Caspase-3 and Bax were significantly increased(P<0.01),while the expression of Bcl-2 was significantly decreased(P<0.01);the apoptotic rate was significantly increased(P<0.01)in the hsa-circ-0001360 overexpression group and the hsa-circ-0001360 + homocysteine overexpression group.(6)In conclusion,hsa-circ-0001360 can promote the apoptosis of human umbilical vein endothelial cells induced by homocysteine.