[Association between lesion location and depressive symptoms in acute ischemic stroke patients using voxel-based lesion-symptom mapping].

Objective: The study aimed to investigate the association between lesion location and post-stroke depression (PSD) in acute ischemic stroke patients. Methods: In this case-control study, acute ischemic stroke patients were recruited from the Department of Neurology, First Affiliated Hospital of the University of Science and Technology of China (USTC), between September 2020 and June 2021. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, the patients were divided into the PSD and non-PSD groups. The 24-item Hamilton Rating Scale (HAMD) was used to evaluate the severity of depression. The Student's t-test, Mann-Whitney test, and Chi-square test were used to compare the clinical baseline characteristics of PSD and non-PSD groups. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and depression occurrence and severity. Results: A total of 70 and 173 patients were admitted to the PSD and non-PSD groups, respectively. The mean age of patients was 59 years (23-86). There were 153 males and 90 females. Univariate analysis showed a significant difference only in Hamilton Anxiety (P=0.025) and Depression (P<0.001) scores between the PSD and non-PSD groups. VLSM analysis identified clusters within the anterior cingulate gyrus (Z=-3.05, P<0.001), left hippocampus (Z=-3.15, P<0.001), and left lingual lobe (Z=-3.08, P<0.001) where lesions were significantly associated with PSD. Additionally, the severity of PSD was associated with damage in the anterior cingulate gyrus (Z=-3.64, P<0.001), left hippocampus (Z=-3.51, P<0.001), left lingual lobe (Z=-4.18, P<0.001), and pericalcarine cortex (Z=-3.65, P<0.001). Conclusion: VLSM demonstrated that lesion location could be used to predict the occurrence of PSD in patients with acute ischemic stroke.

[Prognostic evaluation value of (18)F-FDG PET-CT in Hodgkin's lymphoma after treatment].

Objective: To investigate the prognostic value of (18)F-fluorodeoxygen-D-glucose-positron emission tomography /computerized tomography ((18)F-FDG-PET-CT) in Hodgkin's lymphoma (HL) at the end of first-line treatment (PET-end), by comparing the ratio of maximum standardized uptake value (SUV(max)) of lesion and liver SUV (rLL), SUV(max) reduction between baseline PET (PET-0) and PET-end (ΔSUV(max)), and Deauville 5-point scale (5-PS). Methods: Patients with HL newly treated in our hospital from August 2006 to December 2015 were retrospectively analyzed. All the patients enrolled in the study underwent post-treatment FDG PET-CT. The rLL and ΔSUV(max) were calculated, and all the cases were scored using Deauville 5-PS. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point value, and survival curves according to different PET-CT assessment methods were estimated using the Kaplan-Meier analysis. The prognostic efficacy of different PET-CT assessment methods was compared, and DeLong test was used to verify it. Kaplan-Meier method and multivariate analysis using the Cox proportional hazards model were performed to analyze the potential independent risk factors. Results: There were 5 patients progressed within a 3-year follow-up. In the three PET-CT assessment methods, the predictive value of rLL and Deauville 5-PS were significant effective. ROC analysis for rLL as a progression predictor showed an optimal cut-point of 1.29. Deauville 5-PS=4 and rLL=1.29 showed the best prognostic accuracy. The sensitivity of rLL and Deauville 5-PS were both 80.0%, and the specificity of each was 98.0% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of rLL were 66.7% and 98.7%, while the PPV and NPV of 5-PS were 44.4% and 98.7%. The 3-years progression-free survival (PFS) rates of rLL≥1.29 group and rLL<1.29 group were 33.3% and 98.7%, with significant difference (P<0.001). The 3-years PFS rates of post-treatment Deauville 5-PS<4 group and Deauville 5-PS≥4 group were 98.7% and 55.6%, with significant difference (P<0.001). The prognostic evaluation efficacy of rLL was positively correlated with that of Deauville 5-PS (r=0.75, P<0.05). Area under curves (AUC) of rLL and Deauville 5-PS were 0.93 (95%CI: 0.825-1.000) and 0.91 (95%CI: 0.757-1.000), respectively. DeLong test showed the significant difference between the two methods (P<0.05). The univariate analysis results showed that clinical baseline stage, post-treatment rLL and Deauville 5-PS were associated with the prognoses of HL patients (P<0.05). The multivariate analysis results showed that post-treatment rLL and Deauville 5-PS were independent prognostic factors of HL (P<0.05). Conclusions: The rLL and Deauville 5-PS are potential prognostic factors for HL response assessment. The new semi-quantitative method rLL has methodological advantages over visual analysis, and it is a good supplement for Deauville 5-PS. rLL can improve prognostic evaluation accuracy of PET-CT and is useful to early identify patients with HL at a high risk of relapsing after first-line treatment.

[Relationship of C1QA level and therapeutic effect and prognosis of DLBCL patients treated with R-CHOP].

Objective: To investigate the relationship between plasma levels of complements before treatment and the clinicopathological feathers and prognoses of diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab (R)-CHOP or R-CHOP-like therapy. Methods: The clinicopathological data of 105 DLBCL patients treated in cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2016 were collected. The plasma samples from 105 DLBCL patients treated with R-CHOP or R-CHOP-like therapy and 80 healthy controls were used to detect 34 complement levels before treatment by utilizing antibody microarray. The relationship between plasma levels of complements and the clinicopathological feathers and prognosis of DLBCL patients were analyzed. Results: The signal values of C1QA and CR1L in patients with international prognostic index (IPI) scores of 3-5 were 1 261.43±138.9 and 2 214.69±98.58, respectively, higher than 950.79±80.19 and 984.67±121.79 in patients with IPI scores of 0~2 (both P<0.05). The levels of C1QA and CR1L in the non-complete response (CR) group were 1 165.43±98.56 and 2 263.13±145.63, respectively, higher than 914.70±100.77 and 1 821.34±84.68 in the CR group (both P<0.05). Cox regression analysis showed that elevated C1QA signal value was associated with poor progression-free survival (PFS) and poor overall survival (OS) (PFS: HR=2.063, 95%CI: 1.220-3.489, P=0.007; OS: HR=2.23, 95%CI: 1.036~4.798, P=0.040). After IPI correction by Cox multivariate model, the elevated C1QA signal value was still correlated with poor PFS (HR=1.765, 95%CI 1.034~3.013, P=0.037). Conclusions: The baseline plasma levels of C1QA and CR1L are correlated with IPI scores and therapeutic effects of DLBCL patients treated with R-CHOP. The baseline plasma level of C1QA has a certain predictive value for the prognostic evaluation of DLBCL.

[Preliminary research on long non-coding RNA related signaling pathways regulated by SIRT1 in human trabecular meshwork cells].

Objective: To explore the possible mechanism of silent information regulator 1 (SIRT1) in regulating the function of human trabecular meshwork cells (HTMCs). Methods: Experimental study. HTMCs were transfected with SIRT1-overexpressed lentivirus and control lentivirus at the optimal multiplicity of infection, respectively. The total RNA was extracted, and the long non-coding RNA (lncRNA) microarray was used to detect the expression of lncRNAs. The differentially expressed lncRNAs were analyzed by bioinformatics. Real-time PCR was used to verify the microarray results. Student's t-test was used for comparison between groups. Results: Compared with the control group, there were 636 up-regulated lncRNAs and 2 246 down-regulated lncRNAs in the SIRT1 overexpressed group (all P<0.05). Gene ontology analysis showed that SIRT1 regulated extracellular matrix, cell metabolism, proliferation and apoptosis of HTMCs. Kyoto encyclopedia of genes and genomics pathway analysis indicated that differential lncRNAs induced by SIRT1 were involved in 19 signal pathways, including Notch signaling pathway, mitogen-activated protein kinase signaling pathway, inflammatory mediator regulation of tyrosinase-associated protein channels and extracellular matrix-receptor interaction. Conclusion: SIRT1 could have effects on the function of HTMCs through regulating lncRNAs in multiple signaling pathways, including Notch signaling pathway, mitogen-activated protein kinase signaling pathway, etc. (Chin J Ophthalmol, 2021, 57: 215-222).

[The effect of ovarian function suppression on the psychological status of breast cancer patients under 35 years old in China].

Objective: To explore whether the addition of ovarian function suppression in endocrine therapy of Chinese breast cancer patients under 35 years old will affect the psychological state. Methods: This cross-sectional study enrolled 91 Chinese postoperative breast cancer patients aged 35 years or younger. The depression and anxiety state of patients were assessed by Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7), and their sociodemographic characteristics were collected. Results: Among the 91 patients, 61 were receiving ovarian function suppression (OFS) treatment, 30 were not. Among the 30 patients with out OFS treatment, 2 had PHQ-9 score ≥8, 28 had PHQ-9 score < 8, 1 had GAD-7 score ≥10, and 29 had GAD-7 score < 10. Among the 61 patients with OFS, 19 had PHQ-9 score ≥8, 42 had PHQ-9 score < 8, 8 had GAD-7 score ≥10, and 53 had GAD-7 score <10. The incidence of depression was 6.7% and 31.1% in the non-OFS group and OFS group, respectively (P=0.018). The incidence of anxiety in the two groups was 3.3% and 13.1%, respectively (P=0.174). Univariate analysis showed that the incidence of depression was significantly higher in patients with OFS (P=0.018). After taking into account the sociodemographic factors, pathological stage and treatment of the patients, multivariate analysis showed that the administration of OFS was still significantly related to the incidence of depression (OR=9.14, 95% CI=1.52~55.16, P=0.016). There was no significant difference in the incidence of anxiety (P=0.174). Conclusions: For Chinese young breast cancer patients under 35 years old, the use of OFS in the adjuvant endocrine therapy may lead to a significant increase in the incidence of depression. We should pay attention to the evaluation and monitoring of the psychological state of this population.

[Programmed cell death-1 inhibitor combined with rituximab in refractory or relapsed diffuse large B-cell lymphoma: a preliminary efficacy and safety analysis].

Objective: To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitor combined with rituximab in the treatment of refractory or relapsed diffuse large B-cell lymphoma (rrDLBCL) patients. Methods: The efficacy and safety of rrDLBCL patients treated with PD-1 inhibitor combined with rituximab as salvage therapeutic regimen after initially treated with rituximab, cyclophosphamide, anthracycline, vincristine and prednisone (R-CHOP) regimen in Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College from October 2018 to Janurary 2020 were retrospectively analyzed.Patient who received at least one dose of PD-1 inhibitor combined with rituximab treatment and obtained the efficacy and safety evaluation were included. Results: A total of 22 patients were enrolled in this study. The median age was 51.5 years and the median number of prior treatment regimen was 2. The median time to progression (TTP) for the initial R-CHOP treatment was 9.3 months and the median interval time of rituximab administrations between the previous and the research regimen was 5.5 months. Patients were classified as germinal center B cell (GCB) origin (n=8), non-GCB origin (n=9) and primary mediastinal large B cell lymphoma (PMBCL, n=5). Four patients were double-expression lymphoma, one patient were triple-hit lymphoma. Nine patients had PD-L1 immunohistochemical staining and the proportion of PD-L1 positive tumor cells were 1%-90% for eight patients and negative for one patient.The objective response rate (ORR) and complete response rate (CR) were 72.7% (16/22) and 13.6% (3/22), respectively. The median progression free survival (PFS) was 8.0 (95%CI: 7.0-14.5) months, and overall survival (OS) was not reached. For the 17 patients of non-specific DLBCL, the ORR was 64.7% (11/17), the estimated median PFS was 4.0 (95%CI: 0-8.8) months, the 1-year PFS and OS rates were 39.2% (95%CI: 19.4%-43.4%)and 81.3% (95%CI: 71.4%-91.1%), respectively. All of 5 PMBCL cases achieved ORR, among them, one case was CR and 4 cases were partial responase (PR), and their PFS were 16.4, 9.3, 8.3, 7.9and 3.0 months, respectively. One patient had National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 grade 3 hypophysitis and one patient had NCI CTCAE grade 3 interstitial pneumonia. Conclusion: For rrDLBCL patients who have underwent rituximab treatment previously, PD-1 inhibitor combined with rituximab regimen shows a promising efficacy and tolerability, which can be a potential treatment option.

[Comparison the efficacy and prognosis of different first-line treatment for elderly diffuse large B-cell lymphoma].

Objective: To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups. Results: A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, ß(2)-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group (P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years (P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group (P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, ß(2)-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis (P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma (P<0.05 for both). Conclusions: The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

[Impact of portal vein thrombosis on the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis].

Objective: To explore whether portal vein thrombosis affects the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis. Methods: Hospitalized patients who received endoscopic therapy to prevent re-bleeding from ruptured gastroesophageal varices due to hepatitis B-related liver cirrhosis during 2013 to 2017 were selected, and followed up for 1 year after treatment for re-bleeding and survival status. Patients were divided into thrombotic and non-thrombotic group according to whether they were combined with portal vein thrombosis at the time of initial admission. The baseline data characteristics of the two groups were analyzed. The 1-year re-bleeding rate and survival rate of the two groups were compared by Kaplan-Meier survival analysis. The other risk factors for re-bleeding after endoscopic variceal therapy were evaluated by univariate and multivariate regression. Results: A total of 124 cases with re-bleeding from ruptured gastroesophageal varices due to hepatitis B-related liver cirrhosis were included. The average age was 50.7 years old. 81.5% (101 cases) were male, and 24.2% (30 cases) were combined with portal vein thrombosis. There were no statistically significant differences between the thrombotic and the non-thrombotic group in the average age, gender, liver function classification, transjugular portal pressure gradient, antiviral treatment, and non-selective ß-blockers. Kaplan-Meier analysis of the re-bleeding rate after endoscopic treatment indicated that the incidence of non-bleeding in patients with thrombotic group at 60 days, 180 days and 1 year was significantly lower than that in the non-thrombotic group [86.7%, 80.0%, 56.7% vs. 95.7%, 93.6%, 87.2% (P = 0.000 1)]. Analysis of the location of portal vein thrombosis showed that the bleeding rate in the main portal trunk, left and right branches and superior mesenteric vein had increased significantly after endoscopic treatment, while the splenic vein had no effect on the bleeding after endoscopic treatment. Univariate and multivariate regression analysis indicated that age (HR 1.05, 95% CI: 1.01-1.09, P = 0.02) and thrombosis in the main portal trunk, left and right branches (HR 4.95, 95% CI: 2.05-11.95, P < 0.01) were independent risk factors for re-bleeding at 1 year after endoscopic treatment. Conclusion: Portal vein thrombosis is an independent risk factor that affects the efficacy of endoscopic treatment in preventing re-bleeding from ruptured gastroesophageal varices in hepatitis B-related liver cirrhosis and the risk of re-bleeding increases significantly after endoscopic treatment in patients with thrombosis.

[MicroRNA-1 regulates fibronectin expression in human trabecular meshwork cells under oxidative stress].

Objective: To investigate the expression of microRNA-1 (miR-1) and its regulatory function on fibronectin (FN) in human trabecular meshwork cells (HTMC) under oxidative stress. Methods: Experimental study. After HTMC were treated with 0, 60, 100, 200, 400 µmol/L hydrogen peroxide (H(2)O(2)) for 6 h, respectively, the cells were placed in culture medium for 24 h. The expression of miR-1 and FN mRNA in these cells were detected by real-time quantitative PCR. According to bioinformatics analysis, the target gene of miR-1 is predicted to be FN; pcDNA3/pri-miR-1 vectors, pcDNA3/enhanced green fluorescent protein (EGFP)-FN-3'UTR vectors and pcDNA3/EGFP-FN-3'UTRmut vectors were constructed. pcDNA3/pri-miR-1 were co-transfected with pcDNA3/EGFP-FN-3'UTR or pcDNA3/EGFP-FN-3'UTRmut respectively into HTMC. pDsRed2-N1 was taken as internal reference. After 48 h transfection, the absorbance of EGFP and red fluorescent protein (REP) was detected with fluorescence spectrophotometer to explore the effect of miR-1 on FN expression. HTMC was stimulated with 200 µmol/L H(2)O(2) for 24 h after overexpression plasmid of miR-1 was transfected into it, and then FN mRNA and protein levels were detected via real time PCR, Western blotting and immunofluorescence. Data were analyzed via one-way analysis of variance or t test. Results: With the increase of H(2)O(2) concentration, miR-1 decreased (F=390.80, P<0.01) while FN increased (F=13.16, P<0.01). The level of miR-1 in HTMC stimulated by 200 µmol/L and 400 µmol/L H(2)O(2) decreased to 0.608±0.014 (t=21.67, P<0.01) and 0.409±0.020 (t=29.91, P<0.01), respectively, compared with untreated control cells (1.000); whereas, the mRNA levels of FN increased to 1.630±0.233 (t=4.47, P=0.011) and 1.903±0.246 (t=6.15, P=0.003), respectively, compared with untreated control cells(1.000). Through bioinformatics analysis, miR-1 might have candidate binding site in FN mRNA 3'-UTR. Meanwhile, these cells co-transfected with pcDNA3/pri-miR-1 and pcDNA3/EGFP-FN-3'UTRmut (0.562±0.018) had higher EGFP expression than cells co-transfected with pcDNA3/pri-miR-1 and pcDNA3/EGFP-FN-3'UTR (0.329±0.015) (t=17.39, P<0.01). Compared with the control (1.000), after overexpressing miR-1 the mRNA expression and the protein level of FN decreased to 0.294±0.081 (t=11.01, P<0.01) and 0.584±0.022 (t=5.57, P<0.01), respectively. Conclusions: MiR-1 decreases while FN increased in HTMC under oxidative stress. MiR-1 inhibits FN expression through targeting FN 3'-UTR. (Chin J Ophthalmol, 2019, 55: 355-360).

Genome-wide association analysis reveals novel loci for hypoxia adaptability in Tibetan chicken.

The Tibetan chicken (TBC), an indigenous chicken breed of the Tibetan Plateau, has adapted to its hypoxic, high-altitude environment over hundreds of years. The objective of this study was to identify the polymorphisms and genes associated with adaptation to hypoxia in this chicken breed. In the present study, samples were collected during days 18-21 of the incubation period from both surviving chicks and dead embryos, all of which were hatched under hypoxic conditions. A genome-wide association study was conducted using the Illumina iSelect 60K SNP array with a case-control design, in which the case group consisted of the dead chicken embryos (n = 54) and controls were the surviving chicks (n = 82). Four significant SNPs were detected at the genome-wide level (P < 0.05), and the results indicated that fork head box G1 (FOXG1) was the main candidate gene. The lead SNP NC_006092.4:g.33368893T>C was confirmed with a polymerase chain reaction-restriction fragment length polymorphism analysis of 122 cases and 212 controls. A chi-square test showed a significant association between NC_006092.4:g.33368893T>C and hatchability under hypoxic conditions (P < 0.01). Our results revealed novel polymorphisms and a candidate gene associated with hypoxic adaptation, facilitating further study in this field.

[The development of biosimilars in oncology].

With the extensive application in clinical practice, biological medicine plays a significant role in both treatment and supportive care in oncology. With the expiration of original drug patents, biosimilars emerge. The biosimilars are defined as biological drugs that are be highly similar but not identical to the biological reference. Their development and evaluation procedure are different from those of small molecular chemical generics. Biosimilars are expected to reduce the health care costs worldwide. The booming developments of biosimilars, such as rituximab, trastuzumab and bevacizumab in medical oncology can optimize the clinical strategies, offer patients more treatment options and reduce the medical expenditure. In this article, we review the advances in the field of biosimilars, especially focus on the challenges and opportunities of biosimilars in clinical oncology.

[Effects of prophylactic chemotherapy on outcomes and prognosis of patients older than 40 years with invasive mole].

Objective: To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients. Methods: One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group, while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group). The general clinical data (including age, clinical stage, risk factor score), treatment, outcomes and relapse of patients were retrospectively compared between two groups. Results: (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old. Ratio of clinical stageⅠ-Ⅱ were 3/11 versus 29.8% (31/104), clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2% (73/104). Ratio of risk factor score 0-6 were 11/11 versus 84.6% (88/104), risk factor score >6 were 0 versus 15.4% (16/104). There were no significant statistical differences between two groups in age, clinical stage or risk factor score (all P>0.05). (2) Treatment: the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002). There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of ß-hCG, consolidation chemotherapy courses, total therapeutic chemotherapy courses or ratio of hysterectomy (all P>0.05). (3) Outcomes and relapse: between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group, the complete remission rate were 11/11 versus 98.1%(102/104), the relapse rate were 0 versus 1.0%(1/102). There were no significant difference between the two groups in outcomes or relapse rate (P>0.05). Conclusions: Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years. Prophylactic chemotherapy may not significantly improve patients' prognosis, in which increased sample size is required in further study.

Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

Disparities in postpartum readmission by patient- and hospital-level social risk factors in the United States: a retrospective multistate analysis, 2015-2020.

BACKGROUND: Postpartum readmission is an area of focus for improving obstetric care and reducing costs. We examined disparities in all-cause 30-day postpartum readmission by patient- and hospital-level factors in the United States. METHODS: We conducted a retrospective cohort study using 2015-2020 records from the State Inpatient Databases from four states. Generalized linear mixed models were constructed to estimate the effects of individual patient- and hospital-level factors on adjusted odds of 30-day readmission after controlling for confounders. Stratified analyses by delivery and anesthesia type (New York only) and interaction models were performed. RESULTS: Black mothers were more likely than White mothers to be readmitted within 30-days postpartum (aOR 1.57, 95% CI 1.52 to 1.61). Mothers with public insurance had increased odds of readmission compared with those with private insurance (Medicare: aOR 2.13, 95% CI 1.95 to 2.32; Medicaid: aOR 1.14, 95% CI 1.11 to 1.17). Compared with mothers in the lowest income quartile, those in the highest quartile experienced a 14% lower odds of readmission (aOR 0.86, 95% CI 0.83 to 0.89). There were no significant associations between hospital-level characteristics and readmission. Black mothers were more likely to be readmitted regardless of delivery type and most combinations of delivery and anesthesia type. Black mothers from the highest income quartile were more likely to be readmitted than White mothers from the lowest income quartile. CONCLUSION: Substantial disparities in 30-day postpartum readmissions by patient-level social factors were observed, particularly amongst Black mothers. Action is needed to address and mitigate disparities in postpartum readmission.

[Outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network].

Objective: To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks' gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021. Methods: This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results: Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions: With the increasing number of extremely preterm infants at 22-25 weeks' gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

[Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units].

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

[Treatment of patent ductus arteriosus in very preterm infants in China].

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

[Regulation of microRNA-126 on the polarization of human macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide].

Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.