This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Limb length discrepancy(LLD) is a common complication after total hip arthroplasty (THA). Good positioning of the prosthesis and suitable soft tissue tension are essential to ensure hip joint stability. Patients will be more satisfied if almost the same length of both lower extremities is achieved. Preoperative comprehensive evaluation of patients is helpful to prevent the occurrence of LLD after surgery. Therefore, the pelvic spine conditions, as well as type and cause of LLD should be analyzed in detail before surgery. During operation, limb length should be adjusted by touching the position of patella, Kirschner's wires positioning and referring to the relationship between the center of femoral head and the tip of greater trochanter. After surgery, it is necessary to clearly distinguish true LLD from functional LLD, and make a reasonable therapeutic plan according to patient's symptoms and the range of differences in limb length. This article reviews the latest literatures based on clinical practice experience and summarizes the research status of LLD after THA, which helps joint surgeons to have an in-depth understanding of this postoperative complication.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Femur ; Femur Head ; Lower Extremity ; Pelvis

Child ; Humans ; Acquired Immunodeficiency Syndrome/drug therapy* ; Retrospective Studies ; Anti-Retroviral Agents/therapeutic use* ; HIV Infections/epidemiology* ; China/epidemiology* ; Anti-HIV Agents/therapeutic use*

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.
Humans ; Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Abelmoschus ; Flavones/pharmacology* ; Podocytes ; Tumor Necrosis Factor-alpha/metabolism* ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Fibrosis ; Threonine/pharmacology* ; Collagen/metabolism* ; Serine/pharmacology* ; Diabetes Mellitus/drug therapy*

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

Objective:To investigate the clinical outcomes of minimally invasive lateral lumbar interbody fusion (LLIF) and the necessity to perform LLIF plus posterior direct decompression in the treatment of severe degenerative lumbar spinal stenosis (DLSS).Methods:In this prospective randomized, controlled trial, we assigned 71 patients, who were 50 to 80 years old, and diagnosed with severe DLSS (Schizas Classification grade C on magnetic resonance imaging), in a 1∶1 ratio to undergo either one-stage LLIF plus posterior internal fixation (treatment group) or CLIF plus posterior internal fixation with laminectomy (control group). Demographic and perioperative data were collected and compared. The clinical outcome measures included Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) score as well as visual analogue scale (VAS). Patients were followed up for at least 1 year.Results:The treatment group included 36 patients with 46 surgical levels, while the control group included 35 patients with 46 surgical levels. The baseline demographic data of the 2 groups were equivalent in preoperative central canal areas, spinal canal anteroposterior diameter, disc height, ODI, ZCQ score for symptom severity and physical function, as well as VAS scores for back and leg pain. The mean operative time, blood loss, drainage volume and hospital stay of the treatment group are significantly less than the control group (157.2±29.1 min vs. 180.6±26.8 min, 75.6±39.1 ml vs. 108.6±43.3 ml, 136.9±73.9 ml vs. 220.5±121.3 ml, 5.3±1.1 d vs. 6.6±2.3 d). There were 2 cases with dura tear and 1 case with wound infection in control group. Thus, the surgical trauma and complications of the control group were more than the treatment group. At 1-year follow-up, the mean ODI score of treatment group improved from 42.24%±10.70% preoperatively to 18.21%±11.49%, the mean ZCQ symptom severity from 2.89±0.38 to 1.61±0.41, the mean ZCQ physical function from 2.31±0.45 to 1.50±0.37, the mean VAS for back from 5.56±1.19 to 1.97±1.13 and the mean VAS for leg from 4.44±1.81 to 0.94±1.26. At 1-year follow-up, the mean ODI score of the control group improved from 43.65%±14.93% preoperatively to 17.36%±12.15%, the mean ZCQ symptom severity from 2.92±0.52 to 1.65±0.39, the mean ZCQ physical function from 2.37±0.52 to 1.55±0.39, the mean VAS for back from 5.63±1.40 to 2.34±1.47, and the mean VAS for leg from 4.37±2.14 to 0.83±1.20. The ZCQ satisfactory score of both groups were not significant different (1.25±0.45 vs. 1.26±0.43, t=0.07, P=0.944). The mean improvement rate of both groups for ODI, ZCQ symptom severity, ZCQ physical function, VAS back and VAS leg at 1-year follow-up were not significant different (55.43%±27.74% vs. 58.36%±25.06%, 43.07%±17.22% vs. 42.66%±12.95%, 32.25%±23.65% vs. 31.71%±23.24%, 62.65%±21.25% vs. 58.37%±22.44%, 78.94%±26.41% vs. 85.45%±20.53%). One adjacent segment disease was found in each group at 1 year follow-up. Conclusion:CLIF+ posterior internal fixation in the treatment of Schizas Grade C DLSS has satisfactory clinical outcome at 1-year follow-up. Laminectomy increases surgical trauma, but does not significantly improve the clinical outcome at 1-year follow-up.

Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.