Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q₁ and Q₃ of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q₁, Q₃) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.
Humans ; Infant, Newborn ; Copper/analysis* ; Selenium ; Iron/analysis* ; Fetal Blood/chemistry* ; Case-Control Studies ; Heart Defects, Congenital

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (^aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (^aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (^aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (^aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.
Case-Control Studies ; Child ; Cohort Studies ; Female ; Heart Defects, Congenital/etiology* ; Humans ; Metals, Heavy ; Pregnancy ; Prospective Studies ; Trace Elements/analysis*

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
Adult ; Aged ; Betacoronavirus ; genetics ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; genetics ; rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; genetics ; rehabilitation ; RNA, Viral ; genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies

Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F=2.669, P=0.044, and adjusted R²=0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t=-2.699, P=0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t=2.550, P=0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t=4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P >0.05). Conclusions In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

Objective: To investigate the incidence of chromosome polymorphisms and their influence on semen quality and sperm DNA integrity in male patients receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). METHODS: We retrospectively analyzed the chromosomal karyotypes and the types and incidence rate of chromosome polymorphisms in 2 370 male patients undergoing IVF/ICSI between June 2016 and June 2018. We classified the patients into groups A (with variation in the secondary constriction region in the autosomal long arm), B (with variation in the short arm of the D/G group chromosomes), C (with interbrachial inversion of chromosome 9) and D (with Y chromosome polymorphisms), and compared the semen parameters and sperm DNA fragmentation indexes (DFI) between the patients with chromosome polymorphisms and those with normal chromosomes. RESULTS: Totally, 154 (6.50%) of the patients undergoing IVF/ICSI were found with chromosome polymorphisms, including 34 cases of secondary constriction variation in the long arm of the autosome (1.43% ［34/2 370］, 22.08% ［34/154］), 82 cases of short arm polymorphisms of the D/G group chromosomes (3.46% ［82/2 370］, 53.25% ［82/154］), 26 cases of interbrachial inversion of chromosome 9 (1.10% ［26/2 370］, 16.88% ［26/154］), 10 cases of Y chromosome polymorphisms (0.42% ［10/2 370］, 6.50% ［10/154］), and 2 cases of mixed chromosome polymorphisms (0.08% ［2/2 370］, 1.42% ［2/154］). The total sperm count was lower in group D than in the other polymorphism groups and the normal chromosome group, but with no statistically significant difference among the five groups (P > 0.05). The sperm progressive motility was also lower in group D than in the other five groups, with statistically significant difference from group B (27.5 ± 13.5 vs. 41.5 ± 21.1, P = 0.027), but not from the other groups (P > 0.05). No statistically significant difference was observed in the sperm DFI between the polymorphism groups and the normal chromosome group (P > 0.05), or among the polymorphism groups (P > 0.05). The proportion of normal semen was lower in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05). The incidence rate of asthenospermia was higher in group D than in the other four groups, but with no statistically significant difference among the five groups (P > 0.05), and so was that of oligoasthenospermia, with statistically significant difference from the normal chromosome group (30.0% vs 8.0%, P = 0.041), but not from the other polymorphism groups (P > 0.05). CONCLUSIONS Short arm polymorphisms of the D/G group chromosomes are the most common type of chromosome polymorphisms in male patients undergoing IVF/ICSI. Polymorphisms of the Y chromosome have a negative effect on semen quality, while those of the other chromosomes do not significantly affect semen quality and sperm DNA integrity.

Liver fibrosis is a tissue repair compensatory response to liver injury caused by various chronic factors, ultimately leading to liver cirrhosis, liver failure and even hepatocellular carcinoma. Abnormal activation of hepatic stellate cells is the cellular basis of liver fibrosis development. Pepstatin Pr, the derivative of pepstatin A, was isolated from Streptomyces sp. CPCC 202950. Our purpose was to investigate the anti-fibrotic activity of pepstatin Pr and explore its molecular mechanism. Hepatic stellate cell LX-2 was stimulated by TGFβ1 and sub- sequently treated with pepstatin Pr. Its cytotoxicity was detected by sulforhodamine B (SRB) assay. The expression of COL1A1, α-SMA and cathepsin D, signaling proteins TGFβ, Smad and YAP/TAZ were detected by Western blot or real-time PCR. The results showed that pepstatin Pr was not cytotoxic to LX-2 cells. And pepstatin Pr significantly reduced the mRNA and protein expression of COL1A1 and α-SMA, which are important liver fibrosis markers. Pepstatin Pr also repressed the protein expression level of cathepsin D, TGFβ1, YAP/TAZ, the phospholation level of Smad2, and YAP nuclear translocation. In conclusion, pepstatin Pr exhibits anti-fibrotic effects in TGFβ1-stimulaed LX-2 cells by mediating YAP-TGFβ-Smad pathway.

Objective To explore the impact of hepatitis B virus infection, intrahepatic cholestasis during pregnancy on the risk of small for gestational age (SGA) and low birth weight (LBW), and analyze the interaction effect. Methods The study was conducted from Jan 2017 to Apr 2018 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. The peripheral blood hepatitis B surface antigen (HBsAg) and total bile acids of pregnant women were determined by chemiluminescence method, unconditional Logistic regression models were used to estimate association between hepatitis B virus infection, intrahepatic cholestasis of pregnancy and the risk of neonate outcomes. Results After adjusting for confounding factors, compared to normal pregnant women, HBV infection alone or ICP alone during pregnancy did not increase the risk of SGA or LBW. The increased risk of born before term SGA (OR=1.76, 95% CI:1.16-2.65, P=0.007) and LBW infants (OR=1.85, 95%CI:1.44-2.38, P<0.001) were observed in pregnant women with HBV infection and ICP, the additive and multiplicative interaction were also observed for before term SGA ［RERI (95% CI) =6.54(0.14-12.94), AP (95% CI) =0.90%(0.68%-1.13%), S (95% CI)=7.03(1.38-42.64)］ and LBW ［RERI (95% CI) =5.69(0.48-10.90), AP (95% CI) =0.76%(0.55%-0.97%), S (95% CI)=8.02(1.92-33.43)］. Conclusions Our results suggest that pregnancy HBV infection combined with ICP increase the risk of SGA and LBW infants. These two risk factors had a synergistic effect.

OBJECTIVETo analyze the clinical manifestations, laboratory findings, treatment and prognosis of patients with hemophagocytic syndrome (HPS).

METHODSA retrospective study was carried out to analyze the underlying disease, clinical characteristics, laboratory findings and outcomes of 46 patients with HPS.

RESULTSThis cohort included 19 cases of HPS secondary to cancer, 11 cases of HPS secondary to infection, 10 cases of suspected malignant lymphoma based on PET-CT findings (without biopsy), and 6 cases of unknown etiology. The coincidence rate of the clinical characteristics of the patients with the indices listed in HPS-2004 criteria were: fever (100%), elevated serum ferritin (100%), cytopenias (93.48%), splenomegaly (91.30%), hemophagocytosis in the bone marrow, spleen or lymph nodes (84.78%), hypofibrinogenemia (67.39%), and hypertriglyceridemia (54.05%). The cases of cancer, infections and unknown etiology showed significant differences in serum levels of ferritin and β2MG (P<0.05), and significant differences were found in triglycerides, LDH, and fibrinogenemia between the nonfatal and fatal cases (P<0.05).

CONCLUSIONHPS can be secondary to various underlying diseases, many associated with Epstein-Barr virus infection. Cancer, especially NK/T-cell lymphoma, is the main cause of HPS. Persistent fever, elevated serum ferritin level and cytopenias are the most sensitive indicators for diagnosis of HPS, and early diagnosis and treatment are critical to lower the mortality rate of this disease.