Objective To investigate the regulatory effect of miRNA-933 on the apoptosis and proliferation of human hepatic stellate cell line LX-2 and its mechanism.Methods Firstly,with human liver tissue for research,gene microarray technology was used to detect the differentially expressed genes in liver tissue between liver cirrhosis/chronic hepatitis B tissue and normal liver tissue,among which the significantly differentially expressed miRNAs were identified,and thus miRNA-933 was determined as the research object.Then,with the human hepatic stellate cell line LX-2 for research,miRNA-933 mimic and inhibitor(miRNA-933 siRNA)were used to construct the LX-2 models of overexpression and knockdown,and the cells transfected with mimic-NC(overexpression)or siRNA-NC(knockdown)were established as the negative control group.Quantitative real-time PCR and Western blot were used to measure the expression levels of miRNA-933 and activation biomarkers;techniques such as cell proliferation assay and flow cytometry were used to investigate the effect and mechanism of miRNA-933 on cell apoptosis,proliferation,and activation.The independent-samples t test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and Bonferroni correction was also performed.Results A total of 18 significantly differentially expressed miRNAs were obtained based on the results of gene microarray,among which miRNA-933 was significantly downregulated(P<0.05).After LX-2 cells were transfected with miRNA-933 mimic or siRNA,compared with the negative control group,miRNA-933 siRNA significantly downregulated the expression of miRNA-933(P=0.000 7),while miRNA-933 mimic significantly upregulated the expression of miRNA-933(P=0.000 3).Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly upregulated the expression of collagen Ⅰ and α-SMA(P<0.001),while miRNA-933 mimic significantly inhibited the expression of collagen Ⅰ and α-SMA(P<0.05).Flow cytometry showed that compared with the negative control group,miRNA-933 siRNA significantly downregulated the apoptosis rate of LX-2 cells(P=0.031 9),and miRNA-933 mimic significantly upregulated the apoptosis rate of LX-2 cells(P=0.005 5).Western blot showed that compared with the negative control group,miRNA-933 siRNA could inhibit the expression of Caspase-3(P=0.006 7)and poly(ADP-ribose)polymerase-1(PARP-1)(P=0.003 0)and upregulate the expression of B-cell lymphoma-2(Bcl-2)in LX-2 cells(P=0.002 0),while miRNA-933 mimic could significantly upregulate the expression of Caspase-3(P=0.011 8)and PARP-1(P=0.049 5)and downregulated the expression of Bcl-2(P=0.002 1).Cell proliferation assay showed that compared with the negative control group,miRNA-933 siRNA could promote the proliferation of LX-2 cells(P=0.011 5),while on the contrary,miRNA-933 mimic could inhibit the proliferation of LX-2 cells(P=0.001 2).Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly inhibited the expression of Kruppel-like factor 6(KLF6)and downregulated the expression of activating transcription factor 4(ATF4),activating transcription factor 3(ATF3),and C/EBP homologous protein(CHOP),while miRNA-933 mimic promoted the expression of the above proteins(all P<0.05).Conclusion This study shows that miRNA-933 may promote cell apoptosis and inhibit cell activation and proliferation by promoting the activation of the KLF6/ATF4/ATF3/CHOP/Bcl-2 signal axis in LX-2 cells.

Objective:To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target.Method:Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve.Result:A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant ( P>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups ( P<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Conclusion:Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.

Objective:To analyze the diagnostic value of IgG anti-A/anti-B antibody titer in the serum of type O pregnant women after absorption of IgG anti-AB antibody for ABO hemolytic disease of fetus and newborn (ABO-HDFN).Methods:From February 2020 to September 2020,235 samples of neonatal hemolytic disease whose mother's blood type O from Beijing Blood Center were selected.The titer of IgG anti-A/anti-B antibody in mother's serum before and after absorption of IgG anti-AB antibody was detected by microcolumn gel card,and the incidence of ABO-HDFN was statistically analyzed.The titer level of IgG anti-A/anti-B antibody and the incidence of ABO-HDFN were compared before and after the absorption of IgG anti-AB antibody,and the diagnostic efficacy of the titer level of IgG anti-A/anti-B antibody in the serum of type O pregnant women after the absorption of IgG anti-A and B antibodies on the incidence of ABO-HDFN was analyzed using the receiver's work characteristic (ROC)curve.Results:Of the 235 neonatal hyperbilirubinemia samples with maternal blood type O,127 were blood type A,38 of which were diagnosed as ABO-HDFN;108 were blood type B,of which 31 were diagnosed as ABO-HDFN.Before and after absorption of IgG anti-AB antibody,there was a significant difference in the titer of IgG anti-A/anti-B antibody (P<0.05).Among the 69 confirmed cases,the incidence of ABO-HDFN increased with the increase of IgG anti-A/anti-B antibody with or without the IgG anti-AB antibody,but the anti-A/anti-B antibody titer≥1:512 before the absorption of IgG anti-AB antibody,while the anti-A/anti-B antibody titer decreased significantly,decreasing by three titers,all≤1∶512.The ROC curve shows that the titers of IgG anti-A/anti-B antibodies before and after absorption of IgG anti-AB antibodies can be used as the efficacy indicators for the diagnosis of ABO-HDFN.However,there was a significant difference in the potency of IgG anti-A/anti-B antibody titer for the diagnosis of ABO-HDFN before and after the absorption of IgG anti-AB antibody (P<0.05).The AUC values were greater than before absorption,indicating that the IgG anti-A/anti-B antibody after the absorption of IgG anti-AB antibody was better than before absorption (P<0.05).Conclusion:The higher the titer of IgG anti-A/anti-B antibody measured after absorbing IgG anti-AB antibody,the higher the incidence of ABO-HDFN. In addition,the efficacy of IgG anti-A/anti-B antibody titer to diagnose ABO-HDFN after absorption of IgG anti-AB antibody is higher than that before absorption.

Systemic lupus erythematosus is a classical autoimmune disease that affects multiple organs and systems. In 2023, a lot of new research progress was made in the pathogenesis, diagnosis, evaluation, and treatment of systemic lupus erythematosus. This review summarizes the major representative achievements.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective:To study the remote multi-disciplinary team (MDT) model in diagnosis and treatment of plague, in order to provide scientific basis for clinical treatment of plague.Methods:A retrospective analysis was made on the diagnosis and treatment process of a case of bubonic plague, a sudden imported Class A infectious disease, which was secondary to septicemic plague, involving a remote MDT team consisting of the Infectious Diseases Department, Intensive Care Unit, Respiratory and Critical Care Department, Cardiology Department, Pharmacy Department, and Nosocomial Infection Department of the General Hospital of Ningxia Medical University.Results:The patient was a middle-aged female who was engaged in herding work on the grassland. The first symptom was a sudden pain in the left lower abdomen for three days, accompanied by chest tightness and shortness of breath. After hospitalization, blood culture indicated Yersinia, abdominal CT indicated left lower abdominal lymph node enlargement, and lymph node puncture fluid was positive for Yersinia pestis nucleic acid. Combined with clinical symptoms and signs, the patient was diagnosed as bubonic plague secondary to septicemic plague, and was isolated for treatment. After remote MDT consultation, comprehensive treatment was given, including anti-infection treatment of streptomycin and ciprofloxacin, short-term application of hormones, nutritional support, and local application of chloramphenicol ointment, etc. Secondary acute pancreatitis occurred during the course of the disease, which improved after symptomatic treatment. Finally, after 20 days of treatment, MDT expert group assessed that it met the discharge criteria. No abnormalities were found in follow-up visits outside the hospital. Conclusion:The remote MDT is effective in the treatment of bubonic plague secondary to septicemic plague, which is worth popularizing.

Objective:To compare the clinical efficacy and safety of conventional transcatheter arterial chemoembolization (TACE) with drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) in treatment of patients with unresectable hepatocellular carcinoma.Methods:The data of patients with unresectable hepatocellular carcinoma who underwent hepatic artery chemoembolization at General Hospital of Ningxia Medical University from July 2019 to April 2020 were retrospectively analyzed. Of 282 patients who were enrolled, there were 233 males and 49 females, aged (55.9±10.0) years. The groups were divided into the conventional TACE group ( n=179) and the DEB-TACE group ( n=103) based on the treatments. The efficacy of the two groups was compared according to the modified response evaluation criteria in solid tumors. Postoperative adverse effects and liver function between the two groups were compared. Results:The differences in comparing the preoperative and postoperative liver function indexes between the two groups were not statistically significant. Patients who died and were lost to follow-up at 6 months after surgery were excluded and 240 patients were excluded in the efficacy analysis, with 148 patients in the conventional TACE group and 92 patients in the DEB-TACE group. At 6 months after treatment in the conventional TACE group, there were 64 patients (43.2%) with complete remission, 18 patients (12.2%) with partial remission, 27 patients (18.2%) with stable disease, and 39 patients (26.4%) with disease progression. In the DEB-TACE group, the corresponding figures were 38 patients (41.3%), 17 patients (18.5%), 26 patients (28.3%), and 11 patients (12.0%), respectively. The efficacy of DEB-TACE was better than conventional TACE with statistically significant differences between the 2 groups (χ 2=8.96, P=0.030). The incidence of postoperative embolic syndrome was 53.1% (95/179) in the conventional TACE group, which was significantly higher than the 34.0% (35/103) in the DEB-TACE group (χ 2=7.34, P=0.007). Conclusion:The efficacy and safety of DEB-TACE for unresectable hepatocellular carcinoma were superior to those of the conventional TACE group.

Systemic lupus erythematosus has always been a research hotspot in the field of autoimmune diseases in China and other countries. In 2022, Chinese and international researchers have made a lot of new progress in epidemiology, pathogenesis, diagnosis and evaluation, and treatment of systemic lupus erythematosus. This review mainly summarizes major representative advances.

OBJECTIVE: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth. METHODS: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del. RESULTS: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women. CONCLUSION The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, First ; Iodide Peroxidase ; Cohort Studies ; Reproducibility of Results ; Fetal Development ; Fetal Weight ; Fetal Growth Retardation ; Ultrasonography, Prenatal

In 2021, Chinese and international researchers have made a lot of new progress in pathogenesis, diagnosis and evaluation, and treatment of systemic lupus erythematosus. This review summarizes major representative advances.