Objective To observe the therapeutic effect of Shenshuai Formula(composed of Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine,Citri Reticulatae Pericarpium,Poria,Atractylodis Macrocephalae Rhizoma,Bambusae Caulis in Taenia,Morindae Officinalis Radix,Centellae Herba,Rhei Radix et Rhizoma,etc.)on patients with chronic kidney disease(CKD)at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type.Methods Seventy patients with CKD at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type were randomly divided into a treatment group and a control group,with 35 patients in each group.The control group was given the conventional western medicine integrated treatment for CKD,and the treatment group was given the Chinese herbal decoction of Shenshuai Formula on the basis of treatment for the control group.The course of treatment for the two groups covered 8 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function indicators of serum creatinine(Scr),blood urea nitrogen(BUN),serum cystatin C(CysC),blood uric acid(UA)and estimated glomerular filtration rate(eGFR),and the level of hypersensitive C-reactive protein(hs-CRP)in the two groups before and after the treatment were observed.Moreover,the TCM syndrome efficacy and clinical safety in the two groups were evaluated.Results(1)During the trial,5 cases in the treatment group and 3 cases in the control group fell off,and eventually a total of 62 patients were included in the trial,including 30 cases in the treatment group and 32 cases in the control group.(2)After 8 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 86.67%(26/30),and that of the control group was 59.38%(19/32).The intergroup comparison showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of TCM syndromes in the two groups were significantly decreased when compared with those before treatment(P＜0.01),and the decrease in the treatment group was more obvious than that in the control group(P＜0.01).(4)After treatment,the renal function indicator levels of Scr,BUN,CysC and UA in the two groups were decreased when compared with those before treatment(P＜0.05),and the level of eGFR was increased when compared with that before treatment(P＜0.05).The intergroup comparison showed that the decrease in the levels of Scr,BUN,CysC and UA and the increase in the level of eGFR in the treatment group were superior to those in the control group(P＜0.05).(5)After treatment,the inflammatory factor level of serum hs-CRP in the two groups was improved when compared with that before treatment(P＜0.05),and the improvement in the treatment group was superior to that in the control group(P＜0.05).(6)During the treatment period,no significant changes in the safety indicators such as blood routine test,stool routine test and occult blood test,liver function,electrolyte,and electrocardiogram were presented in the two groups.Conclusion Shenshuai Formula exerts certain effect in the treatment of patients with CKD at stage 3-4 of spleen-kidney qi deficiency with internal accumulation of turbid-phlegm and stasis type.It can relieve the clinical symptoms of the patients to certain extent,effectively decrease the levels of Scr,BUN,CysC and UA,increase the eGFR,improve renal function,lower the level of serum hs-CRP,reduce the micro-inflammatory state of patients,and delay the progress of the disease.

Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

Objective: This study aimed to investigate whether cytokine profiles and virological markers might add value in monitoring the effects of peginterferon (PEG-IFN) therapy for hepatitis B e-antigen (HBeAg) positive chronic hepatitis B (CHB). Methods: HBeAg positive patients with CHB were treated with PEG-IFN for 48 weeks. Clinical biochemical, and HBV serological indexes, as well as cytokines, were detected at baseline and every 12 weeks. Results: A total of 116 patients with CHB were enrolled in this study; 100 patients completed the 48-week treatment and follow-up, of whom 38 achieved serum HBeAg disappearance, 25 achieved HBeAg seroconversion, 37 showed HBsAg decreases ≥ 1 log ₁₀ IU/mL, 9 showed HBsAg disappearance, and 8 became HBsAb positive. The cytokine levels at baseline and during treatment were similar between the HBeAg disappearance group and non-disappearance group. The disappearance of HBeAg was independently associated with HBeAg levels at weeks 12 and 24, and with the HBeAg decline at week 24 ( P < 0.05). The HBsAg response was independently associated with HBsAg, the HBsAg decline, HBeAg, the HBeAg decline at week 12, and HBsAg at week 24 ( P< 0.05). Conclusion There was no significant correlation between the response to interferon (IFN) and cytokines during PEG-IFN treatment. The changes in virological markers predicted the response to IFN after 48 weeks.
Biomarkers ; Cytokines ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B, Chronic/drug therapy* ; Humans ; Interferon-alpha/therapeutic use* ; Polyethylene Glycols/therapeutic use*

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18^th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (r_s = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (r_s = 0.97, P < 0.01) and in placental (r_s = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (r_s = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. Methods Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1β and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. Results Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1β mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1β mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1β mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. Conclusions HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies