Hepatitis E is the liver inflammation caused by a hepatitis E virus infection.Immunocompetent patients with acute hepatitis E can spontaneously clear the infection,whereas immunosuppressed patients may not be able to clear the hepatitis E virus infection and develop chronic hepatitis.Most patients with hepatitis E are asymptomatic and present only with mild and persistent liver function abnormalities.This article reports a case of hepatitis E in an immunocompetent adult with elevated aminotransferases as the main manifestation.Hepatic fibrosis was detected by hepatic puncture biopsy.This report aims to remind other physicians to evaluate liver fibrosis when encountering acute hepatitis E,especially in patients with chronic liver disease.
Adult ; Humans ; Acute Disease ; Hepatitis E/complications* ; Liver Cirrhosis/etiology*

Objective To investigate the clinical efficacy of Yiqi Huoxue Prescription(derived from Shengyu Decoction)in the treatment of mild cervical spondylotic myelopathy(CSM)with qi deficiency and blood stasis type.Methods A total of 128 patients with mild CSM of qi deficiency and blood stasis type who admitted to Guangdong Provincial Hospital of Chinese Medicine from January 2022 to January 2024 were randomly divided into the control group and the trial group according to the random number table method,with 64 cases in each group.The control group was treated with oral administration of Mecobalamin Tablets,and the trial group was treated with Yiqi Huoxue Prescription orally on the basis of treatment for the control group.The two groups were all treated for four weeks,and then were followed up for three months after the completion of treatment.The CSM scores of the Japanese Orthopedic Association(JOA)and the traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before treatment,after two weeks of treatment,after four weeks of treatment,and three months after the completion of treatment.And then the clinical efficacy,progression of CSM and the incidence of adverse reactions of the two groups were evaluated.Results(1)During the trial,two cases in the control group and three cases in the trial group fell off,and eventually a total of 123 cases were included,62 cases in the control group and 61 cases in the trial group.(2)Three months after the completion of treatment,the total effective rate of the trial group was 93.44%(57/61)and that of the control group was 82.26%(51/62),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the trial group was significantly superior to that of the control group,the difference being statistically significant(P<0.05).(3)After two and four weeks of treatment as well as three months after the completion of treatment,JOA scores in the two groups were increased compared with those before treatment(P<0.05),and JOA scores of the trial group at various time points mentioned above were higher than those of the control group,the difference being statistically significant(P<0.05).(4)After two and four weeks of treatment as well as three months after the completion of treatment,TCM syndrome scores in the two groups were decreased compared with those before treatment(P<0.05),and TCM syndrome scores of the trial group at various time points mentioned above were lower than those of the control group,the difference being statistically significant(P<0.05).(5)During the follow-up period,there was none case of significant aggravation or progression to moderate-severe illness in the two groups,and there were no adverse events such as allergies and gastrointestinal reactions.Conclusion Yiqi Huoxue Prescription exerts certain efficacy in treating patients with mild CSM of the qi deficiency and blood stasis type,and the treatment method is effective on improving the spinal cord function and symptoms of qi deficiency and blood stasis type,and slowing down the progression of disease in the patients,with high safety.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To explore the feasibility and operability in identifying the therapeutic dominant stages of traditional Chinese medicine(TCM)based on subdivision model of disease course.Methods The hierarchical Bayesian model was used to differentiate the disease course of 125 cases of premature ovarian failure(POF),and the disease course of POF were divided into the occult stage,diminished ovarian reserve(DOR)stage,premature ovarian insufficiency(POI)stage,and POF stage.An then the paired sample t-test,Pearson correlation analysis and expert in-depth interview were used for the analysis of the therapeutic effects of TCM for POF at various stages.Results(1)Compared with POF stage,DOR and POI stages were frequently intervened by Chinese patent medicine.(2)In DOR(complicated with POI)stage and POF stage,there was significant difference between the degree of TCM intervention and the therapeutic effect(t =-3.70,P＜0.001).(3)The degree of TCM intervention was positively correlated with treatment outcomes in the DOR stage(r = 0.679,P＜0.001),so did in the POF stage(r = 0.432,P＜0.001),but the correlation in the POF stage was slightly lower than that in the DOR stage.(4)The results of in-depth interviews with experts of TCM gynecology showed that in the concealed phase of POF,the prognosis would be most favorable if TCM regulation and intervention were performed.In the DOR stage and POI stage,treatment with Chinese medicine prescriptions usually brought about better curative effect and prognosis.For the patients at POF stage,the therapeutic effect of TCM depended on the patients'compliance and the treatment course,and the effect was relatively not as good as that of the previous stages.Conclusion In the DOR stage and POF stage,the higher the degree of TCM intervention,the better the prognosis will be achieved for the patients treated with western medicine.In the POF stage,the efficacy of TCM intervention is reduced to a certain extent compared with the DOR stage.The results indicated that it is feasible and operable to identify the TCM therapeutic dominant stages based on the subdivision model of disease course.

Pyroptosis is a newly discovered kind of cell death modality that, due to its association with innate immunity, plays a crucial role in cytolysis and inflammatory cytokine release during host defense against infection. In recent years, studies have shown that pyroptosis plays an important role in the occurrence and development of liver diseases. This article introduces and elaborates on the most recent research progress on pyroptosis in liver diseases based on the morphological features, molecular and pathophysiological mechanisms.

Yellowish sweating disease is one of the fluid-retention diseases recorded in Jin Gui Yao Lve(Synopsis of the Golden Cabinet).The symptoms of yellowish sweating disease are complex,involving multiple visceral lesions,which are caused by interior heat and exterior deficiency,together with the concurrent invasion of pathogens of wind and water.Huangqi Shaoyao Guizhi Kujiu Decoction(mainly composed of Astragali Radix,Paeoniae Radix Alba,Cinnamomi Ramulus and vinegar)and Guizhi Plus Huangqi Decoction(mainly composed of Cinnamomi Ramulus and Astragali Radix)are the classical formula for the treatment of yellowish sweating disease.Both of the formulas have the actions of warming defensive qi and dredging yang,removing fluid retention and resolving dampness.Usually suffering heat in the spleen and stomach,together with carelessness in daily living and wind-water pathogens attacking the exterior,contributes to the key pathogenesis of diabetes mellitus.The clinical manifestations,etiology,occurrence and progression,and prognosis of yellowish sweating disease are similar to those of diabetic complications.Therefore,the treatment of diabetes complications such as diabetic kidney disease,diabetic cardiomyopathy,diabetic peripheral neuropathy,diabetes mellitus complicated with liver dysfunction,diabetic foot,and diabetic retinopathy can follow the therapeutic principles of yellowish sweating disease,and can be achieved by the therapies of clearing heat and purging fire,dispelling cold and removing dampness,and nourishing nutritive yin and harmonizing defensive qi with the appropriate formulas.The exploration of the treatment of diabetes mellitus and its complications from the pathogenesis and symptom characteristics of yellowish sweating disease will expand the thoughts for treating diabetic complications with traditional Chinese medicine.

Objective To observe the value of 5.0T MR susceptibility weighted imaging(SWI)for displaying cerebral small veins and detecting cerebral microbleeds(CMB).Methods Head MR examinations were prospectively performed using both 3.0T and 5.0T MR scanner in 30 stroke patients suspected caused by cerebral small vessel disease.The image quality,effect of displaying cerebral small veins and detecting CMB were compared between 3.0T and 5.0T SWI.Results The image quality scores,signal-to-noise ratios,contrast-to-noise ratios,scores of displaying deep cerebral veins and subcortical veins,the counts of detecting CMB and iron deposition on cortical surface of 5.0T SWI were all higher than those of 3.0T SWI(all P＜0.05).High consistency of CMB positions was found between 3.0T and 5.0T SWI(Kappa=1.0).Conclusion The effect of 5.0T MR SWI for displaying cerebral small veins and detecting cerebral microbleeds were better than 3.0T MR SWI,which could be used to assess stroke caused by cerebral small vascular disease.

Abstract: Objective To explore the risk factors for macrolide unresponsive mycoplasma pneumoniae pneumonia (MUMPP) in children and to develop a model for predicting the risk of MUMPP. Methods Children with mycoplasma pneumoniae pneumonia admitted to the Pediatric Department of Leshan People's Hospital who met the inclusion criteria from March 1, 2023, to December 1, 2023, were retrospectively selected and divided into the responsive group and unresponsive group according to their reactions to macrolides. General patient data, laboratory tests, and imaging findings were collected and compared. Logistic regression analysis was used to analyze the risk factors of the Macrolide unresponsive mycoplasma pneumoniae pneumonia, and R language (R4.2.3) to establish the nomogram model. The goodness of fit, discriminative ability, calibration, and clinical utility of the model were assessed using the Hosmer-Lemeshow goodness of fit test, receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. Results A total of 224 patients were included in the analysis of children. Among them, 156 (70%) were randomly selected as the training set, and the remaining 68 cases (30%) were used as the validation set. Logistic regression analysis revealed that pleural effusion (OR=6.986, 95%CI 1.362-35.847), highest temperature before admission (OR=3.095, 95%CI 1.487-6.439), neutrophil count (OR=1.294, 95%CI:1.103-1.519), C-reactive protein (OR=1.030, 95%CI 1.002-1.058), and procalcitonin (OR=2.899, 95%CI:1.353-6.214) were independent risk factors for MUMPP in children (all P<0.05). A nomogram was established using R software. The Hosmer-Lemeshow goodness of fit tests for the training set and the validation set were χ2=4.018 and χ2=4.657 (all P>0.05), indicating a good fit of the model. The AUC values for the training set and validation were 0.825 (95%CI: 0.755-0.894) and 0.828 (95%CI 0.729-0.928), respectively, suggesting good discriminative ability of the model. Calibration curve analysis suggested that the model had good predictive performance, while decision curve analysis indicated a high clinical application value of the predictive model. Conclusions Pleural effusion, highest body temperature before admission, neutrophil count, C-reactive protein, and procalcitonin are independent risk factors for MUMPP in children. The prediction model constructed based on the above variables has high predictive efficacy and clinical application value.

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*