Bone-related diseases are a group of inflammatory diseases characterized by abnormal bone resorption and formation,with a wide variety of diseases involving age,inflammation,obesity,genetics,radiation,and other pathogenic factors.In recent years,se-nescent cells have become an important mechanism for age-related diseases,and their role in bone-related diseases has attracted the at-tention of researchers.Senescent cells are gradually being used as therapeutic targets for bone-related diseases.In this paper,we pres-ent a review of the mechanism of senescent cells in various types of bone-related diseases,which will provide new strategies for the pre-vention and treatment of bone diseases.

Objective:To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis.Methods:This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions.Results:At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT.Conclusion:FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Bone-related diseases are a group of inflammatory diseases characterized by abnormal bone resorption and formation,with a wide variety of diseases involving age,inflammation,obesity,genetics,radiation,and other pathogenic factors.In recent years,se-nescent cells have become an important mechanism for age-related diseases,and their role in bone-related diseases has attracted the at-tention of researchers.Senescent cells are gradually being used as therapeutic targets for bone-related diseases.In this paper,we pres-ent a review of the mechanism of senescent cells in various types of bone-related diseases,which will provide new strategies for the pre-vention and treatment of bone diseases.

Objective:To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis.Methods:This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions.Results:At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT.Conclusion:FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.

Objective To observe the clinical efficacy of Feisu Granules,and its effects on quality of life,coagulation and immune function in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with syndrome of phlegm-heat and blood stasis of lung.Methods Totally 120 AECOPD patients were divided into observation group and control group according to random number table method,with 60 cases in each group.The control group was given conventional Western medicine treatment,and the observation group received Feisu Granules treatment on the basis of the control group,one bag each time,three times a day,orally.The treatment for both groups lasted for 7 d.The clinical efficacy of both groups were observed.TCM symptom scores,St.George's respiratory questionnaire(SGRQ)score,coagulation function indexes(fibrinogen,D-dimer),and immune function indexes(CD4+,CD8+,CD4+/CD8+)of both groups were compared.The side effects were observed.Results The total effective rate in the observation group(93.10%)was significantly higher than that of the control group(79.66%),with statistical significance(P<0.05).Compared with before treatment,TCM symptom scores,scores of cough,wheezing,venous congestion,and SGRQ score decreased in both groups after treatment(P<0.05);after treatment,the observation group had lower above scores than the control group(P<0.05).Compared with before treatment,both groups showed a decrease in plasma fibrinogen and D-dimer levels after treatment(P<0.05);after treatment,the observation group showed lower levels of plasma fibrinogen and D-dimer compared with the control group(P<0.05).Compared with before treatment,the peripheral blood CD4+ and CD4+/CD8+ levels in both groups significantly increased after treatment,while CD8+ levels significantly decreased(P<0.05);after treatment,the peripheral blood CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group,while CD8+ was lower than those in the control group(P<0.05).Neither group had any drug-related side effects.Conclusion On the basis of conventional Western medicine,the combination of Feisu Granules in the treatment of AECOPD with syndrome of phlegm-heat and blood stasis of lung can significantly improve clinical efficacy,improve patient quality of life,facilitate coagulation function recovery,and enhance cellular immune function.

[Objective[ To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

Dandy-Walker syndrome is one of the posterior fossa malformations, which is easily confused with arachnoid cyst or cerebellar dysplasia in clinical practice, leading to misdiagnosis. Dandy-Walker syndrome is easy to be combined with hydrocephalus, resulting in increased intracranial pressure, increased head circumference, growth retardation, spastic hemiplegia and other manifestations, and can also be accompanied by other nervous system malformations. On February 27, 2021, a child with Dandy-Walker syndrome with growth retardation as the primary manifestation was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. After multiple surgical treatment, the child's hydrocephalus was significantly improved. Through the analysis of the clinical data of the child's operation and the treatment of complications, it is helpful to improve the clinicians' understanding of the surgical treatment of the disease.

Forensic science is looking for clues at a crime scene in order to reconstruct the crime scene.Classic clues include DNA and fingerprints.Forensic microbiology is a branch of forensic medicine that uses microbes as clues,providing us information about lifestyle,circadian rhythms,geographic locations,postmortem intervals,cancers,and oral or systemic diseases.Oral cavity,as the place with the second largest number of microorganisms,can provide researchers with microbial information of each ecological niche,and assist in the prediction,diagnosis and monitoring of oral or systemic diseases.This paper reviews the composition of oral microbiome,the application in oral diseases,systemic diseases and forensic medicine,with the aim of providing some references for the development of forensic microbiology based on oral microbiome.

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Cell Proliferation ; DNA, Mitochondrial ; Energy Metabolism ; Glucose ; Mouth Neoplasms/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism* ; Phosphatidylinositol 3-Kinases ; Reactive Oxygen Species