Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.
Humans ; Autoantibodies/isolation & purification* ; Female ; Breast Neoplasms/immunology* ; Ovarian Neoplasms/immunology*

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

Pregnancy ; Female ; Humans ; Milk, Human ; Overweight/genetics* ; Fatty Acids, Unsaturated ; Fatty Acids ; Adiponectin/genetics*

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.
Humans ; Diabetic Nephropathies/drug therapy* ; Nonprescription Drugs/therapeutic use* ; Qi ; Network Meta-Analysis ; Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Tablets ; Diabetes Mellitus/drug therapy*

OBJECTIVE: To investigate the role of miRNAs in amniotic fluid exosomes in growth and development of fetuses with Down syndrome (DS). METHODS: Amniotic fluid were collected from 20 fetuses with DS and 20 normal fetuses (control) to extract amniotic exosome miRNA. MicroRNA sequencing technique was used to identify the differentially expressed miRNAs between the two groups, for which gene ontology (GO) and pathway analysis was performed. Three differentially expressed miRNAs with the strongest correlation with DS phenotype were selected for qPCR verification. Dual luciferase reporter assay was used to verify the activity of let-7d-5p for targeted regulation of BACH1. RESULTS: We identified 15 differentially expressed miRNAs in DS as compared with the control group, among which 7 miRNAs were up-regulated and 8 were down-regulated. Target gene prediction results showed that the differentially expressed miRNAs targeted 17 DS-related genes. GO analysis revealed that the main functions of the target genes involved protein binding, protein transport, ATP binding, transferase activity and synapses. Pathway analysis revealed that the functional pathways were closely related with the development of the nervous system. qPCR results showed that the expression levels of miR-140-3p and let-7d-5p were significantly lower in DS group than in the control group (P < 0.05), as was consistent with miRNA sequencing results; the expression level of miR-4512 was significantly higher in DS group than in control group (P < 0.05), which was contrary to miRNA sequencing results. The results of double luciferase reporter gene assay confirmed that let-7d-5p was capable of targeted regulation of BACH1 expression. CONCLUSION Let-7d-5p in amniotic fluid exosomes may promote oxidative stress events in the brain of fetuses with DS by regulating BACH1 expression.
Amniotic Fluid/metabolism* ; Down Syndrome/genetics* ; Exosomes ; Female ; Humans ; MicroRNAs/metabolism* ; Pregnancy

Objective: To analyze the change trend of underground dust concentration, the incidence and survival status of pneumoconiosis patients, and provide reference for improving the working environment of dust-exposed workers and the prevention and treatment of pneumoconiosis patients in the future. Methods: In February 2020, a retrospective investigation was conducted on the dust data of underground mining operations in a steel enterprise in Jiangsu Province from 1991 to 2019, and the case data of patients diagnosed with pneumoconiosis from 1956 to 2019 were collected. The time trends of the number of pneumoconiosis patients and dust concentration, the stage of pneumoconiosis and survival status of patients were analyzed. Results: From 1956 to 2019, a total of 241 patients with pneumoconiosis were diagnosed in the steel enterprise. From 1991 to 2019, the annual average dust concentration in the mine showed a downward trend as a whole. Compared with the transportation platform (14.28%, 1447/10132) , the average dust concentration exceeding rate of the mining platform (43.68%, 8415/19263) was significantly higher (χ(2)=2674.84, P<0.01) . The average age of pneumoconiosis patients was (73.54±10.42) years old, and the average working age of dust exposure was (21.41±8.68) years, of which 85 cases (35.27%) survived and 156 cases (64.73%) died. The main type of pneumoconiosis was silicosis (90.46%, 218/241) , and the main stage of pneumoconiosis was the stage I (96.68%, 233/241) ; The higher the stage of pneumoconiosis, the younger the diagnosis age (P<0.01) . The average survival time of patients was (27.264±1.982) years, and the median survival time was 28 years. The cumulative survival rates of patients with pneumoconiosis in different diagnosis time periods were significantly different (χ(2)=35.57, P<0.01) . Conclusion: The improved dust-proof measures have a significant effect on reducing the concentration of underground dust. We need to focus on the dust control of underground mining platforms and the treatment of patients with stage Ⅲ pneumoconiosis.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Child ; Adolescent ; Young Adult ; Adult ; Incidence ; Coal Mining ; Steel ; Retrospective Studies ; Pneumoconiosis/diagnosis* ; Dust ; Occupational Exposure/adverse effects*

Objective: “Same treatment for different diseases” is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. Citrus Grandis Exocarpium (Huajuhong in Chinese, HJH), a famous herbal, is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on “syndrome differentiation and treatment” theory. However, the common mechanism for HJH's treatment of COPD and lung cancer is not clear. Methods: In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build “ingredient-target-signal pathway” network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules. Results: Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer. Conclusion: Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the “Same treatment for different diseases” strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases.

ObjectiveBone marrow-derived mesenchymal stem cells (MSCs) can promote ovarian angiogenesis, improve ovarian insufficiency caused by chemotherapy, and repair ovarian function, while heat shock pretreatment can reduce the apoptosis rate of stem cells and improve the therapeutic effect of stem cells. This study aims to investigate the effect of heat shock pretreatment on MSCs, and further study the effect of heat shock pretreated mesenchymal stem cells on chemotherapy-induced apoptosis of ovarian granulosa cells.Methods1. The bone marrow-derived MSCs of rats were isolated, cultured and identified, and pretreated within a 42 °C water bath for one hour. 2. Cisplatin (5 mg/L) was added to MSCs to simulate the local microenvironment of chemotherapy. MSCs were divided into four groups: blank control group, heat shock control group, model group, and heat shock model group. The effects of heat shock pretreatment on the proliferation, apoptosis and survival rate of MSCs were investigated by CCK-8 method, Hoechst33342/PI, and flow cytometry. 3. We isolate and culture rat ovarian granulosa cells (GCs) to establish an in vitro model of GCs injury under the induction of cisplatin (5 mg/L). The experiment was carried out in four groups: a control group, model group, MSCs model group, HS-MSCs model group. The apoptosis and survival rate were detected by Hoechst33342/PI and flow cytometry, respectively.Results1. The proliferation level and survival rate of MSCs in the heat shock control group were significantly higher than those in the other three groups, and the apoptosis rate was significantly lower than the other three groups (P<0.05). Compared to the model group, the proliferation level of the heat shock model group was significantly increased, and the apoptosis rate was significantly decreased (P<0.05), and the cell survival rate increased; 2. The apoptosis rate of GCs in the HS-MSCs model group was significantly lower than that in the other three groups. Compared to the MSCs model group, the apoptosis rate of GCs in the HS-MSCs model group was significantly decreased (P<0.05).ConclusionHeat shock pretreatment can increase the proliferation level and survival rate of MSCs, and reduce its apoptosis rate. Heat shock pretreated stem cells can effectively inhibit chemotherapy-induced apoptosis of ovarian granulosa cells.

Background: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. Methods: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. Results: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. Conclusion Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

AIM:To observe the changes of autophagy-related indexes during endoplasmic reticulum stress (ERS) induced by dithiothreitol (DTT) and its effect on apoptosis in human normal hepatocytes.METHODS:LO2 cells were treated with DTT at 2.0 mmol/L for 0, 6, 12 and 24 h to induce ERS.The expression of glucose-regulated protein 78 (GRP78) , protein kinase R-like endoplasmic reticulum kinase (PERK) , activating transcription factor 4 (ATF4) , C/EBP homologous protein (CHOP) , autophagy-related gene 12 (Atg12) , autophagy-related gene 5 (Atg5) and microtubule-associated protein 1 light chain 3 (LC3) at mRNA and protein levels was determined by real-time PCR and Western blot.The apoptosis was analyzed by flow cytometry.The formation of autophagosomes was observed under transmission electron microscope.After the LO2 cells were pretreated with rapamycin at 400 nmol/L for 1 h and treated with DTT at 2.0mmol/L for 24 h, the effect of rapamycin pretreatment on the apoptosis was analyzed by flow cytometry.RESULTS:After treatment with DTT at 2.0 mmol/L for 6, 12 and 24 h, the mRNA and protein levels of GRP78, PERK, ATF4, CHOP, Atg12, Atg5 and LC3 in the LO2 cells were significantly higher than those in 0 h group (P<0.05).At the same time, the ratio of LC3Ⅱ/LC3Ⅰwas also increased after DTT treatment (P<0.05).Observation under transmission electron microscope showed that autophagosomes were found in the LO2 cells treated with DTT for 6, 12 and 24 h.After DTT treatment for 6, 12 and 24 h, the apoptosis rate of LO2 cells was significantly higher than that in DTT 0 h group, while the apoptosis induced by DTT was significantly decreased after rapamycin pretreatment (P<0.05).CONCLUSION:ERS induces autophagy and rapamycin pretreatment alleviates the apoptosis of LO2 cells to some extent.