With the rising incidence of diabetes， diabetic kidney disease （DKD） has become a significant global health burden. Although current prevention and treatment strategies can partially delay the progression of DKD， the risk of patients advancing to end-stage renal disease remains high. Since the concept of the "gut-kidney axis" was first introduced at the International Congress on Dialysis in 2011， research on the role of gut microbiota in the pathogenesis of DKD has received increasing attention. This review summarizes the current research on gut microbiota， explores the mechanisms through which it contributes to DKD development， and outlines clinical approaches for DKD prevention and treatment based on the "gut-kidney axis" theory. Evidence indicates that dietary interventions， intake of probiotics or prebiotics， use of metformin and novel antidiabetic drugs， and application of traditional Chinese medicine （TCM） compound formulas can effectively improve gut microbiota composition， influence metabolite production， and restore the intestinal mucosal barrier. These interventions can further regulate intestinal innate immunity and inflammatory responses， thereby modulating the progression of DKD. Despite challenges posed by the traditional oral administration of water-decocted TCM compound formulas and the complexity of their ingredients， increasing evidence suggests that TCM may indirectly affect the occurrence and development of DKD by modulating gut microbiota. This finding provides a new perspective on the potential mechanisms of TCM in DKD treatment and may offer novel strategies for DKD prevention and therapy.

Traditional Chinese medicine （TCM） offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome（CKM）， demonstrating unique advantage. Building on previous work in managing diabetes， its complications， and chronic kidney disease， our team has proposed a five-phase evolution theory of "constraint， heat， deficiency， stasis， and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness， constraint transforming into heat， heat damaging qi and yin， stasis accumulated in the collateral vessels， and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM， it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory， and incorporate the "2-5-8" prevention and treatment strategy， which combines prevention with treatment， tailors interventions to different phases， and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.

OBJECTIVE: To explore the safety and effectiveness of the "talus home technique (THT) " in the surgery of pronation open ankle fractures (POAF). METHODS: A retrospective analysis was conducted on 14 patients with POAF admitted between January 2023 and December 2023 who met the selection criteria. There were 7 males and 7 females; age ranged from 26 to 58 years, with a median age of 53 years. Injury causes included 9 cases of traffic accident injury, 3 cases of fall from hight injury, and 2 cases of crush injury. There were 5 cases of type Ⅱ, 6 cases of type ⅢA, and 3 cases of type ⅢB according to Gustilo classification; and 6 cases of pronation-abduction grade Ⅲ and 8 cases of pronation-external rotation grade Ⅳ according to Lauge-Hansen classification. Emergency first-stage debridement of the ankle joint was performed, followed by second-stage open reduction and internal fixation surgery. The THT was used through a limited incision on the lateral malleolus to restore the height of the lateral malleolus, rotational alignment, and anatomical relationship of the distal tibiofibular syndesmosis (DTFS). Wound healing was observed postoperatively. At 4 months postoperatively, weight-bearing anteroposterior, lateral, and mortise view X-ray films and CT scans of both ankles were reviewed to measure the medial clear space (MCS), tibiofibular clear space (TFCS), distal fibular tip to lateral process of talus (DFTL), and anterior/posterior syndesmosis distances of DTFS, and the quality of reduction of ankle fractures was evaluated. Ankle joint function was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and active dorsiflexion/plantar flexion range of motion were recorded at last follow-up. RESULTS: After second-stage internal fixation, 8 patients achieved wound healing by first intention, 1 case had skin edge necrosis, 2 cases had local skin necrosis, 1 case had extensive medial soft tissue defect, and 2 cases developed medial wound infection with sinus formation. All 14 patients were followed up 13-24 months (mean, 16.8 months). Postoperative X-ray films showed 1 case of delayed union of the lateral malleolus, which healed after bone grafting at 12 months; the remaining 13 cases achieved clinical union at 12-32 weeks (mean, 21.5 weeks). At 4 months postoperatively, X-ray films and CT examination showed no significant differences in MCS, TFCS, DFTL, and anterior/posterior syndesmosis distances of DTFS between the healthy and affected sides ( P>0.05), with no poor DTFS reduction. AOFAS ankle-hindfoot score ranged from 80 to 95, with an average of 87.7; ankle range of motion ranged from 10° to 25° (mean, 19.6°) in dorsiflexion and from 32° to 50° (mean, 41.2°) in plantar flexion. CONCLUSION THT is safe and effective in POAF surgery. It can restore lateral malleolar height and rotational alignment, enhance DTFS reduction quality, and obtain satisfactory short-term functional recovery of the ankle.
Humans ; Male ; Female ; Middle Aged ; Ankle Fractures/surgery* ; Adult ; Retrospective Studies ; Fracture Fixation, Internal/methods* ; Pronation ; Fractures, Open/surgery* ; Talus/surgery* ; Treatment Outcome ; Debridement/methods* ; Ankle Joint/surgery* ; Open Fracture Reduction/methods*

OBJECTIVE: To evaluate the safety and effectiveness of reducing posterior malleolar fractures via the modified Rammelt transfibular approach. METHODS: A retrospective analysis was conducted on 26 patients with ankle fractures who met the selection criteria and were admitted between September 2023 and May 2024. There were 13 males and 13 females, aged from 14 to 59 years (median, 43.5 years). Causes of injury included traffic accident (1 case), falls (7 cases), and sprains (18 cases). Time from injury to operation ranged from 1 to 13 days (mean, 3.9 days). According to the Lauge-Hansen classification, there were 5 supination-external rotation type Ⅲ fractures and 21 supination-external rotation type Ⅳ fractures. According to the Bartoníček classification for posterior malleolar fractures, there were 12 type Ⅱ fractures, 10 type Ⅲ fractures, and 4 type Ⅳ fractures. During operation, the fracture was exposed via the modified Rammelt transfibular approach; then, the fracture reduction was achieved under direct vision using techniques such as towel clip traction, posterolateral compression, and lifting with a posterior transverse periosteal elevator; finally, the fracture was fixed using anteroposterior cannulated screws or Kirschner wires. The incision healing was observed after operation. At 4 months after operation, X-ray film and CT were reviewed to evaluate the quality of fracture reduction. The medial clear space, tibiofibular clear space, and the anterior/posterior tibiofibular syndesmotic distances were measured. At last follow-up, the ankle function was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the range of motion. RESULTS: The marginal necrosis occurred in 2 lateral malleolar incisions, and superficial infection occurred in 1 lateral malleolar incision; the remaining incisions healed by first intention. All 26 patients were followed up 13-21 months (mean, 15.6 months). X-ray films showed that fractures in 25 patients achieved clinical union within 3-8 months (mean, 5.4 months); 1 case had delayed union of the lateral malleolus. At 4 months after operation, no significant difference was found between the injured and healthy sides in the medial clear space, tibiofibular clear space, or the anterior/posterior tibiofibular syndesmotic distances ( P>0.05). No malreduction of the posterior malleolus or the tibiofibular syndesmosis occurred. At last follow-up, the AOFAS score ranged from 80 to 100 (mean, 91.9). The range of motion ranged from 17° to 22° (mean, 21.0°) in active ankle dorsiflexion and from 40° to 49° (mean, 44.6°) in plantar flexion. Internal fixator was removed in 12 patients at 1 year after operation, with no ankle instability occurring. Ankle joint degeneration was observed in 1 patient at last follow-up. CONCLUSION The modified Rammelt transfibular approach is a safe and reliable technique. It enables precise reduction under direct vision, improves the quality of reduction for the distal tibial articular surface and the tibiofibular syndesmosis, and provides satisfactory ankle functional recovery in short-term follow-up.
Humans ; Male ; Female ; Adult ; Ankle Fractures/diagnostic imaging* ; Middle Aged ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Adolescent ; Treatment Outcome ; Young Adult ; Bone Screws ; Ankle Joint/surgery* ; Fibula/surgery* ; Range of Motion, Articular

Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

Objective:To investigate whether hsa_circ_0054595(circRTN4)is involved in glomerulosclerosis of lupus nephri-tis(LN)by regulating monocyte-derived TNF-α.Methods:RT-qPCR and immunofluorescence were used to detect the expression of TNF-α in monocytes of LN patients,and fluorescence in situ hybridization(FISH)was used to detect the expression of circRTN4.THP1 cells were transfected with circRTN4-siRNA and negative control NC-siRNA,respectively.RT-qPCR and Western blot were used to detect the expression of TNF-α in THP1cell,and ELISA was used to detect the expression of TNF-α in THP1 culture superna-tant.THP1 cells were transfected with mircoRNA mimics,and the expression of TNF-α was detected by Western blot.The direct bind-ing of miR-486-3p to TNF-α and circRTN4 were verified by reversion experiment and dual luciferase reporter gene experiment.MRL/lpr mice were injected with circRTN4 recombinant adeno-associated virus via tail vein,and the expression of circRTN4 in peripheral blood mononuclear cells of the mice was detected by RT-qPCR.ELISA was used to detect the expression of serum TNF-α.HE staining and PAS staining were used to observe the pathological changes,and immunofluorescence was used to detect the expression of FN.Results:The expressions of TNF-α and circRTN4 were increased in monocytes of LN patients(P<0.05).The expression of TNF-α in THP1 was significantly increased in the LN group(P<0.01).Knockdown of circRTN4 inhibited the expression and secretion of TNF-α(P<0.05),and this effect was achieved by binding to miR-486-3p(P<0.01).In vivo,knockdown of circRTN4 in peripheral blood monocytes of MRL/lpr mice reduced the expression of TNF-α in serum(P<0.05),and improved glomerular cell proliferation and FN deposition.Conclusion:Highly expressed circRTN4 in monocytes promotes the expression of TNF-α by binding to miR-486-3p,and participates in the occurrence and development of glomerulosclerosis in LN.

Objective We aimed to investigate(i)the preventive and therapeutic effects of Huogu Muli Prescription(HGMLP),a Chinese medical compound consisting of epimedii folium,drynariae rhizoma,and ostreae concha,on postmenopausal osteoporosis(PMOP)rats and(ii)whether it exerts its effects by regulating the osteoclast-osteogenesis balance.Methods Forty-eight female Sprague-Dawley rats were randomly divided into the following six groups:(i)the sham-operated group,(ii)the model group,(iii)the Qianggu Capsule group,(iv)the calcium carbonate group,and(v,vi)the HGMLP low-dose and high-dose groups(n = 8 rats per group).After adaptive feeding,rats in all groups except the sham-operated group were treated with bilateral ovarian castration to establish the PMOP model.Each day,rats in the Qianggu Capsule group received 0.054 g/kg Qianggu Capsule suspension intragastrically,rats in the calcium carbonate group received 1.670 g/kg calcium carbonate suspension intragastrically,and rats in the HGMLP low-dose and high-dose groups received 0.188 g/kg and 0.375 g/kg HGMLP intragastrically.Rats in the sham-operated group and the model group received an equal volume of normal saline intragastrically.After 90 consecutive days,serum estradiol(E2),estrogen receptor α(ERα),procollagen typeⅠN propeptide(PINP),and tartrate-resistant acid phosphatase 5b(TRACP-5b)were detected by ELISA.Total antioxidant capacity(T-AOC),superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels were measured by colorimetry.Bone mineral density(BMD),trabecular number(Tb.N),trabecular separation/spacing(Tb.Sp),trabecular thickness(Tb.Th),and structure model index(SMI)were measured by Micro-CT,and the microstructure of cancellous bone was observed.The expressions of osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK),RANK ligand(RANKL),phosphorylation of forkhead box O3(FoxO3α),Wnt2,β-catenin,and peroxisome proliferator-activated receptor γ(PPARγ)in rat femur tissue were detected by Western blotting.Results(i)The serum levels of E2 and ERα increased in the Qianggu Capsule group and HGMLP groups,compared with the model group(all P<0.05).(ii)Compared with the model group,the serum levels of PINP,TRACP-5b decreased and PINP/TRACP-5b increased in both the Qianggu Capsule group and HGMLP high-dose group(all P<0.05).(iii)The activities of T-AOC,AOD,and CAT in the Qianggu Capsule group and HGMLP groups were higher than those in the model group,while the content of MDA lower(all P<0.05).(iv)Compared with the model group,the femoral BMD,Tb.Th,and Tb.N increased in the Qianggu Capsule group and HGMLP groups,while the femoral Tb.Sp and SMI decreased(all P<0.05);the femoral BMD increased and the Tb.Sp decreased in the calcium carbonate group(all P<0.05).(v)The protein expressions of RANKL,RANK,FoxO3α,and PPARγ in the Qianggu Capsule group and HGMLP groups were lower than those in the model group,while the protein expressions of OPG,Wnt2,and β-catenin were higher(all P<0.05).Conclusion HGMLP can significantly increase estrogen levels,inhibit osteoclast differentiation,and inhibit bone resorption in the PMOP rats.It also alleviates oxidative stress,promotes osteogenic differentiation,inhibits lipogenic differentiation,improves bone formation,and recovers the balance between osteoclasts and osteoblasts,thus achieving prevention and treatment of PMOP.The potential mechanism of HGMLP may be related to regulation via the OPG/RANKL/RANK or FoxO3α/Wnt2/β-catenin/PPARγ pathways.

Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

Objective: To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments. Methods: Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot. Results: Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells. Conclusion P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.