ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective:To analyze the clinical features and risk factors for renal injury in children with antineutrophil cytoplasmic antibody (ANCA)-positive IgA vasculitis (IgAV).Methods:A case-control study was conducted. Seventy-two ANCA-positive IgAV children hospitalized at the Children′s Hospital of Chongqing Medical University from January 2017 to October 2022 were enrolled as the ANCA-positive group. Propensity score matching (1∶4) using the nearest neighbor was performed with age and gender as covariate, and 288 cases ANCA-negative IgAV children were included as the ANCA-negative group. Patients with renal injury were named ANCA-positive IgAV nephritis (IgAVN) group and ANCA-negative IgAVN group, respectively. The ANCA-positive IgAVN group was further divided into myeloperoxidase (MPO) group and proteinase 3 (PR3) group based on the type of ANCA. Clinical data including manifestations, laboratory tests, renal injury, and prognosis were collected. Comparisons between groups were performed using independent sample t-tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests. Kaplan-Meier curves were used to assess differences in the time to renal injury onset, and multivariate logistic regression was performed to identify independent risk factors for renal injury. Results:Among the 72 ANCA-positive IgAV children (41 males, 31 females, age of 7.7 (5.3, 11.2) years), no significant difference in age or gender was observed compared to the ANCA-negative group (both P>0.05). The ANCA-positive group had higher IgM levels, a higher incidence of recurrent rash, and shorter thrombin time (all P<0.05). Among children with renal injury, the ANCA-positive group showed significant differences in the incidence of hematuria, clinical classification, and grade A prognosis compared to the ANCA-negative group (all P<0.05), but no difference was found in the time to renal involvement onest or renal pathology (all P>0.05). The MPO group had higher rates of microscopic hematuria, gross hematuria, acute renal insufficiency, glomerular sclerosis, and grade B prognosis compared to the ANCA-negative IgAVN group (all P<0.05), with a later onset of renal involvement ( P<0.05). Elevated serum creatinine ( OR=1.08, 95% CI 1.03-1.14) and shortened thrombin time ( OR=0.71, 95% CI 0.55-0.92) were independent risk factors for renal injury in ANCA-positive IgAV children (all P<0.05). Conclusions:Children with ANCA-positive IgAV are more likely to experience recurrent rash. MPO-ANCA-positive IgAVN children have higher risks of hematuria, acute kidney injury and glomerular sclerosis, with later-onset but poorer renal prognosis compared to ANCA-negative IgAVN children. Higher serum creatinine levels and shorter thrombin time may be associated with renal injury in children with ANCA-positive IgAV.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Objective:To compare the effects of manual acupuncture(MA),electroacupuncture(EA),and moxibustion on knee joint cartilage morphology,serum inflammatory factors interleukin(IL)-6 and IL-10,matrix metalloproteinase 13(MMP13),and intestinal flora composition in knee osteoarthritis(KOA)model rats.Methods:Forty male specific-pathogen-free Sprague-Dawley rats aged seven weeks were randomly divided into a normal group(n=8)and a KOA modeling group(n=32).The KOA model was established using sodium iodoacetate induction.The KOA modeling rats were further randomly divided into a model group,an MA group,an EA group,and a moxibustion group,with 8 rats in each group.In the MA,EA,and moxibustion groups,interventions targeting the right Futu(ST32)and Zusanli(ST36)were performed for 15 min,once every other day,for 14 sessions.The normal and model groups were bundled on the self-made fixation frame for 15 min.The rat knee joint diameter was measured on the 8th day of adaptive feeding,after successful modeling,and after the 14th intervention.Lequesne behavioral scoring was performed after successful modeling and after the 14th intervention.After the 14th intervention,hematoxylin-eosin(HE)staining and Masson staining were performed with the cartilage sections of the right knee joint.The pathomorphological changes of the rat joint cartilage were observed and quantified by Mankin's score.Enzyme-linked immunosorbent assay was used to detect the rat serum levels of IL-6,IL-10,and MMP13.Additionally,16S rDNA sequencing was used to detect the composition of rat fecal flora.Results:Compared to the normal group,the right knee joint diameter and the Lequesne score were significantly increased in the model group(P<0.01).Compared to the model group,the right knee joint diameter and the Lequesne score of rats in the MA,EA,and moxibustion groups were significantly reduced(P<0.01),with no significant differences among the three intervention groups(P>0.05).HE staining and Masson staining revealed disordered cartilage structure in the model group,which was improved following interventions in the MA group,EA group,and moxibustion group.Mankin's score was significantly higher in the model group versus the normal group(P<0.05)while significantly lower in the MA,EA,and moxibustion groups versus the model group(P<0.05).Serum analysis showed elevated IL-6 and MMP13 levels and reduced IL-10 level in the model group versus the normal group(P<0.05).Compared to the model group,the serum IL-6 level was significantly reduced(P<0.05),and the IL-10 level was significantly increased(P<0.05)in the MA,EA,and moxibustion groups,but without statistical differences among the three intervention groups(P>0.05);moreover,the MMP13 level in the moxibustion group was significantly lower than that in the model group(P<0.05).The alpha diversity analysis of intestinal flora showed no statistical difference in the number of operational taxonomic units(OTUs)and alpha diversity index among groups(P>0.05).Intestinal flora beta diversity analysis revealed significant differences among groups(P<0.05).Intestinal flora composition analysis showed significantly increased relative abundance of Lactobacillus(P<0.05)and significantly decreased relative abundance of Eubacterium_coprostanoligenes(P<0.05)in the model group compared to the normal group;compared to the model group,the relative abundances of Firmicutes,Lactobacillus,and Romboutsia in the MA,EA,and moxibustion groups were significantly reduced(P<0.05);the relative abundance of Bacteroidetes and Lachnospiraceae_NK4A136 in the MA group increased significantly(P<0.05);Bacteroidetes and Ruminococcaceaae_UGC-005 increased significantly in the moxibustion group(P<0.05).Conclusion:MA,EA,and moxibustion effectively reduced knee joint swelling,improved cartilage tissue morphology,optimized intestinal flora composition,down-regulated expression levels of serum pro-inflammatory factors IL-6 and MMP13,and increased expression level of anti-inflammatory factor IL-10 in KOA rats.Among them,moxibustion exhibited the most obvious regulatory effect on inflammatory factors.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.