Objective:To study the risk factors, cerebral hemodynamics and clinical outcomes of extremely and very preterm infants with severe intraventricular hemorrhage (IVH).Methods:From January 2019 to December 2019, premature infants with gestational age (GA) <32 w admitted to our hospital were assigned into severe IVH group and non-severe IVH group. Risk factors for severe IVH were analyzed. According to clinical outcomes, severe IVH group was further assigned into improvement subgroup and no-improvement subgroup. Cerebral hemodynamic parameters were compared between the two groups.Results:A total of 346 eligible neonates were enrolled in this study. The incidence of severe IVH was 11.0% (38 cases). The incidences of Grade Ⅲ and Ⅳ IVH were 8.7% (30/346) and 2.3% (8/346), respectively. Multivariate logistic regression analysis showed that CA < 28 w ( OR=4.365, 95% CI 1.055~18.054), 5 min Apgar score ≤7 ( OR=8.749, 95% CI 2.214~36.042), chorioamnionitis ( OR=3.245, 95% CI 1.127～9.344), PaCO 2 fluctuation within 1 h >25 mmHg ( OR=7.728, 95% CI 1.738~80.907) and vasoactive drugs usage ( OR=10.883, 95% CI 3.746~31.621) were the risk factors of severe IVH. 20 cases in severe IVH group were improved at discharge and 12 cases showed no improvement at discharge. Improvement subgroup showed quicker reduction of the middle cerebral artery flow resistance and faster recovery of the mean flow velocity than the no-improvement subgroup. Conclusions:GA <28 w, 5 min Apgar score ≤7, chorioamnionitis, PaCO 2 fluctuation within 1 h >25 mmHg and vasoactive drugs usage are risk factors of severe IVH in extremely and very preterm infants. Cerebral hemodynamic monitoring may provide initial assessment for the clinical outcomes for severe IVH.

Objective:To evaluate the post-marketing safety and immunogenicity of a 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods:From September 2020 to June 2021, a clinical trial of single-dose PPV23 was conducted in people ≥3 years old in Centers for Disease Control and Prevention of Guizhou, Hunan and Fujian provinces. Blood samples were collects from the subjects before and 30 d after vaccination. ELISA was used to quantitatively detect IgG antibodies against capsular polysaccharides of 23 Streptococcus pneumoniae serotypes in serum samples. The adverse events (AEs) were monitored within 7 d after vaccination. Results:A total of 409 subjects were enrolled and included in safety analysis. Except for one with antibody level inversion, the other 408 participants were included in immunogenicity analysis. The levels of antibodies against the 23 Streptococcus pneumoniae serotypes were all increased after vaccination by an average of 4.24 folds. The two-fold growth rates of the antibodies ranged from 51.72% to 96.81% with a total two-fold growth rate of 78.59%. The overall rate of AEs was 27.14% (111/409). Local AEs were mainly pain, induration, redness and swollen. No serious adverse events related to vaccination occurred. Conclusions:This study preliminarily demonstrated the good immunogenicity and safety of PPV23 vaccine.

Objective:To discuss the protective effect of Syringin (SYR) on myotube cell atrophy induced by lipopolysaccharide (LPS) and its molecular mechanism.Methods:After C2C12 myoblasts were differentiated into myotubes, they were divided into normal control group, model group and syringin group according to the random number table method. The cultured medium of model group and syringin group were added with LPS with a concentration of 200 ng/ml; the cultured medium of the syringin group was also added with 10 μmol/L syringin for 24 h. CCK8 was used to detect cell viability. In cell supernatant, NO release was detected with Griess and TNF-α level was detected by ELISA kit. The expression of NF-κB, PPAR γ1, MyHC were detected by Western blot.Results:Compared with the model group, the viability of cells [(101.08±8.92)%, (79.53±5.19)% vs. (69.07±7.16)%] in the 10 μmol/L and 100 μmol/L syringin groups were significantly increased ( P<0.01 or P<0.01), of which 10 μmol/L syringin had better effect. Compared with the model group, the level of NO [(2.92±0.33) μmol/L vs. (3.57±0.41) μmol/L] in the syringin group was significantly decreased after 6 hours of intervention ( P<0.01), and the cells in the syringin group after 24 hours of intervention, the level of TNF-α [(2.73±0.29) pg/ml vs. (4.15±0.29) pg/ml] was significantly decreased ( P<0.01), and the protein expression of cellular NF-κB (0.95±0.24 vs. 1.16±0.28) was significantly decreased ( P<0.05), the protein expression of MyHC (0.79±0.15 vs. 0.70±0.16) was increased ( P<0.05). Conclusion:SYR could inhibit the inflammatory response induced by LPS, promote the activity of myotubes, and antagonize the damage of LPS to myotube cells.

Objective:To study the clinical features and high-risk factors of early-onset sepsis (EOS) in extremely preterm and super preterm infants.Methods:Retrospective study.Clinical data of extremely preterm and super preterm infants with the gestational age < 32 weeks were obtained from the clinical database of breast milk quality improvement registration in the Woman′s Hospital of Nanjing Medical University between January 2019 and December 2019.EOS cases were enrolled in the EOS group, and the remaining were enrolled in the control group.Risk factors for EOS, distribution of pathogenic bacteria, clinical features, complications, and outcomes between groups were analyzed.Measurement data were compared between the independent sample t-test.Counting data between groups were compared by the Chi- square test, corrected Chi- square test or Fisher′ s exact test.Multivariable Logistic regression model was used to analyze the risk factors of EOS in extremely and super preterm infants. Results:A total of 347 eligible neonates were recruited, including 22 neonates with EOS and 325 neonates without EOS.The incidence rate of EOS was 6.3%.Multivariate Logistic regression analysis showed that cesarean delivery was the protective factor for EOS ( OR=0.277, 95% CI: 0.091-0.847); while maternal prenatal infection ( OR=2.750, 95% CI: 1.053-2.908), fetid amniotic fluid ( OR=3.878, 95% CI: 1.344-11.187), chorioamnionitis ( OR=4.363, 95% CI: 1.552-12.236) and intubation ( OR=3.883, 95% CI: 1.133-13.306) were risk factors for EOS.A total of 22 strains of pathogenic bacteria were cultured in the EOS group, including 14 strains (63.6%) of Gram-positive bacteria, 7 strains (31.8%) of Gram-negative bacteria and 1 strain (4.6%) of fungus.The acute respiratory distress syndrome (54.5%), poor peripheral circulation perfusion (54.5%), mental depression (50.0%), and procalcitonin>0.5 mg/L (40.9%) were the main clinical features of EOS.Compared with the control group, extremely preterm and super preterm infants with EOS had a significantly higher rate of septic shock, disseminated intravascular coagulation, severe intraventricular hemorrhage (≥Ⅲ), acute respiratory distress syndrome (ARDS), and bronchopulmonary dysplasia( χ2=36.696, 33.255, 13.534, 95.455 and 3.886, respectively; all P<0.05). Conclusions:Maternal perinatal infection, odor amniotic fluid, chorioamnionitis and delivery room tracheal intubation are high-risk factors for preterm and super preterm infants with EOS, which can be prevented by cesarean section.Gram-positive cocci are the main pathogenic bacteria of EOS.ARDS and poor peripheral circulation perfusion are the main clinical manifestations of EOS, which increase the occurrence of severe intracranial hemorrhage and other complications.

ObjectiveTo investigate the protective effect of Zhizi prescription （ZZP） on carbon tetrachloride （CCl₄）-induced acute and subacute liver injury and its mechanism. MethodAcute and subacute liver injury animal models were induced. C57 mice were randomly divided into a normal group， model group， obeccholic acid group， ZZP high-dose （0.5 g·kg^-1） group， and ZZP low-dose （0.25 g·kg^-1） group. According to the experiment design， the serum and liver tissue of mice were collected after the last administration. Hematoxylin-eosin （HE） and Sirius staining was used to observe the liver pathological changes. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， liver homogenate hydroxyproline （Hyp）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels were determined by kit. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the liver tissue were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expressions of collagen 1A1 （Col1a1）， collagen 3A1 （Col3a1）， fibronectin （FN）， transforming growth factor β receptor Ⅱ （Tgfbr2） and α-smooth muscle actin （α-SMA） in the liver tissue. ResultIn terms of the acute liver injury， as compared with the normal group， the levels of ALT， AST， TBIL and MDA in the model group were significantly increased （P<0.01）， while the activity of liver SOD was significantly decreased （P<0.01）. Compared with model group， the ZZP high-dose and low-dose groups both significantly reduced the degree of liver cell injury， and protected the acute liver injury induced by CCl₄. The ZZP high-dose group had a better effect than the ZZP low-dose group. In terms of the subacute liver injury， the levels of ALT， AST， MDA，TNF-α and IL-6 in the model group were significantly increased （P<0.01）， while the activity of liver SOD was significantly decreased （P<0.01）. As compared with the model group， liver Hyp content in the ZZP high-dose and low-dose groups was significantly decreased （P<0.01）， and the collagen deposition in liver of both groups was significantly reduced. The ZZP high-dose group also significantly down-regulated the mRNA expressions of α-SMA， Col1a1， Col3a1， FN， and Tgfbr2 in the liver of mice （P<0.05， P<0.01）. ConclusionZZP effectively protects the acute and subacute liver injury induced by CCl₄， and the protective effect is proportional to its concentration. The mechanism may be related to the increase of the activity of antioxidant enzymes in the liver tissue， the decrease of the level of lipid peroxidation， and the inhibition of inflammatory response， thus reducing collagen deposition and improving early liver fibrosis.

Objective:To evaluate the outcomes of cardiopulmonary resuscitation in the delivery room (DR-CPR) at birth for very/extremely low birth weight infants (VLBWI/ELBWI).Method:PubMed, Embase, Cochrane Library, CNKI, VIP database and Wanfang database were searched. The search time limit is from the establishment of the database to October 26, 2020. Search and screen all the literature on the short-term and long-term outcomes of VLBWI/ELBWI who require DR-CPR and conduct quality evaluations. Review Manager 5.3 software was used to perform the Meta analysis. Egger's test in Stata Software 15.0 was used to draw a funnel plot and validate publication bias.Result:A total of 16 studies were included, all in English. 5 661 VLBWI/ELBWI received DR-CPR, and 73 438 VLBWI/ELBWI did not receive DR-CPR. The Meta analysis showed: DR-CPR for VLBWI/ELBWI was associated with an increased risk of mortality ( RR=2.30, 95% CI 1.89~2.82, P<0.05), grade 3 or 4 intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) ( RR=1.92, 95% CI 1.56~2.36, P<0.05),bronchopulmonary dysplasia (BPD) ( RR=1.18,95% CI 1.04~1.33, P<0.05), neurodevelopmental impairment (NDI) ( RR=1.25, 95% CI 1.14~1.38, P<0.05). However, it did not increase the risk of retinopathy of prematurity (>grade 2)( RR=1.31, 95% CI 0.96~1.79, P=0.09). The ELBWI was analyzed in subgroups, and the results were consistent with the overall results. Conclusion:CPR at birth for VLBWI/ELBWI was associated with higher risk of mortality, IVH (grade 3 or 4) or PVL, BPD, NDI.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis, and surgical resection is the preferred method for the treatment of HCC, but it has a limited therapeutic effect on advanced HCC, while systemic treatment plays an important role in the treatment of advanced unresectable HCC. This article summarizes the advances in systemic therapy for unresectable liver cancer in China and globally in recent years, including a variety of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, and nivolumab). The analysis shows that for patients with unresectable HCC, systemic therapy can prolong the survival time of patients to a certain extent, and combined treatment regimen has become a new research hotspot. Individualized systemic treatment strategies will be further explored in the future.

Objective:To explore the value of laparoscopic and endoscopic cooperative surgery with the patient lying on supine position under general anesthesia in the operation of type I Mirizzi syndrome with choledocholithiasis.Methods:From Jan 2018 to Jan 2020, 53 cases of Mirizzi syndrome with choledocholithiasis undergoing laparoscopic and endoscopic cooperative surgery (preLC+ ERCP+ EST) at the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed.Results:53 patients successfully underwent LC without conversion to open surgery, and 2 patients failed in ERCP + EST attempt, with a success rate of 96.2%. One patient developed pancreas pseudocyst as a result of post-operative hemorrhagic necrotizing pancreatitis. Two patients suffered from chronic pancreatitis. Three patients complaining postoperative upper abdominal discomfort were finally diagnosed as stump cystic duct inflammation by MRCP, and no abnormalities were found in the follow-up of the remaining cases.Conclusion:Laparoscopic and endoscopic cooperative surgery in the treatment of patients with type I Mirizzi syndrome combined with choledocholithiasis is minimally invasive and effective.

Objective:To investigate the current situation of human milk (HM) feeding in hospitalized very low and extremely low birth weight infants.Methods:The study retrospectively extracted the data of 601 infants with birth weight <1 500 g, and admitted within 24 hours after birth to the Neonatal Intensive Care Unit of Nanjing Maternity and Child Health Care Hospital from January 2016 to December 2018. The infants were grouped into exclusive mother′s-own-milk (MOM) group, donor human milk (DHM) group (partial or none MOM), and mixed (HM and formula) feeding group according to the feeding strategy. Qualitative and quantitative variables in the three groups were compared with One-way ANOVA, Kruskal-Wallis test, Chi-square test or Fisher exact test. Kappa and McNemar test were used for consistency testing.Results:Among the 601 infants (309 boys and 292 girls), 6 (1.0%) infants had never been fed with MOM. The gestational age and birth weight were (29.3±1.9) weeks and 1 260(1 115, 1 400) g in 601 infants. A total of 8 (1.3%) infants were grouped into MOM group, 542 (90.2%) were grouped into DHM group, and 51 (8.5%) were grouped into mixed feeding group. The percentage of enteral feedings with MOM in the stage of hospitalization 1-7 d, 8-14 d and 15-28 d were 73.6% (42.9%, 86.7%), 97.5% (78.6%, 100.0%) and 99.3% (93.0%, 100.0%), respectively ( H=414.95, P<0.01), and the pairwise comparison suggested that the stage of hospitalization 1-7 d was the lowest (adjusted both P<0.05). The average weight adjusted daily dose of MOM were 9.7 (4.3, 18.2), 59.1 (26.5, 93.5) and 116.0 (60.3, 142.6) ml/(kg·d) in the stage of hospitalization 1-7 d, 8-14 d and 15-28 d, respectively ( H=759.75, P<0.01), and the pairwise comparison suggested that the stage of hospitalization 1-7 d was the lowest (adjusted both P<0.05). The weight adjusted daily dose of MOM in exclusive MOM group, DHM and Mixed feeding group were 95.2 (40.0, 117.2), 82.9(53.6, 103.1) and 55.7 (16.6, 97.5) ml/(kg·d), respectively ( H=10.78, P=0.005).Additionally, the percentage and weight adjusted daily dose of MOM showed a general consistency of 0.703 ( P>0.05, Kappa=0.408). Conclusions:The rate of exclusive MOM feeding is low, especially during the first 7 days of hospitalization. The percentage of total enteral feedings with MOM and the average weight adjusted daily dose of MOM can well evaluate the situation of HM feeding during hospitalization quantitively.

Objective To study the distribution of preterm infants' body temperature at admission and its effects on the clinical outcome.Method The distribution of preterm infants' body temperature at admission and its effects on their clinical outcome were searched in the Cochrane library,PubMed,Embase,Wanfang,CNKI,VIP from the initial establishment of these databases to June 2018.The quality of the included studies were assessed.STATA 12.0 software was used for statistical analysis.The odds ratio (OR) and 95％ confidence interval(CI) were used for continuous variables.Result A total of 16 studies (including 15 clinical trials) with 47 113 cases were included.The incidences of different admission temperatures were as follows:＜35℃:10.3％ (7.6％～13.1％),＜36℃:45.3％ (35.0％～55.5％),＜36.5℃:63.5％ (51.8％～75.2％),36.5～37.4℃:35.1％ (25.6％～44.7％),≥37.5℃:4.2％ (2.6％～5.7％).Compared with normothermia (36.5～37.4℃),hypothermia (＜35℃,35～35.9℃,36～36.4℃) increased the mortality,with the OR and 95％CI as follows:6.10(4.88～7.62),1.96(1.45～2.66),1.31(1.16～1.48);hyperthermia (≥37.5℃) was not associated with higher mortality (OR =0.98,95％CI 0.73～1.32,P=0.91).Compared with normothermia (36.5～37.4℃),hypothermia (＜36℃) increased the risks of severe retinopathy of prematurity (ROP),necrotizing enterocolitis (NEC),sepsis,periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH),with the OR and 95％CI as follows:ROP:1.70(1.45～2.00),NEC:1.27(1.08～1.49),sepsis:1.44(1.28～ 1.61),PVL/IVH:1.26(1.07～1.48),but not the risk of bronchopulmonary dysplasia (BPD,OR =1.03,95％CI 0.76～1.38,P=-0.87).Compared with normothermia (36.5～37.4℃),the temperature between 36～36.4℃ did not increase the risk of severe ROP,NEC,BPD,sepsis,PVL/IVH,with the OR and 95％CI as follows:1.19(0.92～ 1.54),1.01(0.86～1.18),0.91(0.68～1.22),1.02(0.91～1.14),0.98(0.85～1.14).Conclusion Admission temperature of ＜35℃,35～35.9℃,and 36～36.4℃ increased the mortality risk compared with 36.5～37.4℃,and the lower admission temperature,the higher mortality risk.Admission hypothermia (＜36℃) increased the risk of severe ROP,NEC,sepsis,PVL/IVH compared with normothermia (36.5～37.4℃).