ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

PURPOSE: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

OBJECTIVE: To establish a genotyping method for Diego, MNS and Kell blood groups based on quantitative real-time PCR (qPCR) technology, and preliminarily apply it to the screening of rare blood groups in blood donors. METHODS: Blood group gene standards containing heterozygous and homozygous alleles were prepared by blood group serological and PCR-SBT methods. Specific amplification primers and hybridization probes were designed, and explore to establish the qPCR method for detecting Diego, MNS, and Kell blood group genotypes. Then the established qPCR method was used to identify blood group genotypes of 186 blood donor samples. RESULTS: A method based on qPCR technology was established to identify Dia/Dib, S/s and K/k blood group antigens. The genotyping results of the gene standard samples were consistent with the serological testing results and genotypes detected by PCR-SBT. qPCR testing of 186 samples identified 11 cases of DI*A/B heterozygosity and 19 cases of GYPB*S/s heterozygosity, and the rest were DI*B/B, GYPB*s/s, KEL*02/02 homozygosity. No rare blood group genotypes of DI*A/A, GYPB*S/S, KEL*01.01/01.01 were found. CONCLUSION The established qPCR method is suitable for genotyping on Diego, MNS and Kell blood group, and it can be used for batch screening of blood donors and the establishment of rare blood group bank.
Humans ; Genotype ; Genotyping Techniques/methods* ; Real-Time Polymerase Chain Reaction/methods* ; Blood Group Antigens/genetics* ; Kell Blood-Group System/genetics* ; Blood Donors ; Blood Grouping and Crossmatching/methods* ; Erythrocytes ; MNSs Blood-Group System/genetics*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins