ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

ObjectiveTo investigate the clinical efficacy and mechanisms of Qigui Didang decoction in the treatment of kidney collateral stasis syndrome in patients with stage Ⅲ-Ⅳ diabetic kidney disease （DKD） in a real-world setting. MethodsPatients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome admitted to Beijing Aerospace General Hospital from January 2022 to December 2024 were selected for clinical study. According to treatment methods， patients were divided into the Qigui Didang decoction group （Qigui Didang decoction + conventional treatment） and the control group （conventional treatment alone）. A 1∶1 propensity score matching （PSM） method was used to reduce bias caused by confounding factors. Clinical efficacy， traditional Chinese medicine （TCM） symptom scores， renal function indicators， mRNA expression related to pathway mechanisms， glycolipid metabolism indices， and adverse reactions were compared between the two groups. ResultsA total of 120 patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome were included， including 62 cases in the Qigui Didang Decoction group and 58 cases in the control group. Before matching， there were statistically significant differences between the two groups in DKD stage， baseline urinary albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， and estimated glomerular filtration rate （eGFR） （P<0.05）. After matching， 47 cases were included in each group， and there was no statistically significant difference in baseline data between the two groups. After matching， the total clinical effective rate of the Qigui Didang decoction group was significantly higher than that of the control group （χ²=4.681， P<0.05）. Compared with data before treatment， the scores of primary and secondary TCM symptoms in the Qigui Didang decoction group were significantly decreased （P<0.05）. Compared with data before treatment， serum creatinine （SCr）， 24 h-UTP， and UACR levels were significantly decreased， while eGFR was significantly increased in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， the mRNA expression of silent information regulator 1 （Sirt1） was significantly upregulated， while the mRNA expression of nuclear factor-kappa B （NF-κB） and tumor suppressor protein p53 （p53） was significantly downregulated in the Qigui Didang decoction group （P<0.05）. Compared with data before treatment， fasting plasma glucose （FPG）， 2-hour postprandial plasma glucose （2 hPG）， glycated hemoglobin A1c （HbA1c）， total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C） levels were decreased， while high-density lipoprotein cholesterol （HDL-C） levels were increased （P<0.05）. There was no statistically significant difference in adverse reactions between the two groups. ConclusionQigui Didang decoction combined with conventional treatment can significantly improve renal function， glycolipid metabolism， and TCM syndromes in patients with stage Ⅲ-Ⅳ DKD with kidney collateral stasis syndrome， with good safety. The mechanism may be related to the regulation of the Sirt1/NF-κB/p53 signaling pathway.

With the rapid advancement of hemodynamic indices and monitoring technologies, their classification methods and application processes have become increasingly complex. Currently, no unified standard hasbeen established, making it difficult to fully meet the clinical requirements for hemodynamic management. To assist in hemodynamic monitoring assessment and therapeutic decision-making in critically ill patients, the Critical Hemodynamic Therapy Collaborative Group, in conjunction with the Critical Ultrasound Study Group, has jointly developed the Standard for the Application of Hemodynamic Monitoring Techniques in Critical Care. The first part of this standard systematically categorizes hemodynamic indicators into flow indicators, pressure and its derivative indicators, and tissue perfusion indicators, while elaborating on the clinical application of each. The second part establishes a standardized clinical implementation pathway for hemodynamic monitoring. It proposes a tiered monitoring strategy-comprising basic, advanced, indication-specific, and special scenario monitoring-tailored to different clinical settings. It emphasizes the central role of critical care ultrasound across all levels of monitoring and establishes hemodynamic assessment standards for organs such as the brain, kidneys, and gastrointestinal tract. This standard aims to provide a unified framework for clinical practice, teaching, training, and research in critical care medicine, thereby promoting standardized development within the discipline.

Objective To investigate the clinical characteristics of patients with clinical and subclinical Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia(PBMAH).Methods A retrospective analysis was performed on the clinical data of 198 patients with Cushing's syndrome caused by PBMAH diagnosed in the First Medical Center of Chinese PLA General Hospital from January 2004 to October 2024.According to clinical manifestations,the patients were classified into clinical type Cushing's syndrome(n=61)and subclinical type Cushing's syndrome(n=137),and the clinical characteristics of the two types were compared.Results The mean age at diagnosis of patients with PBMAH-induced Cushing's syndrome was(53.5±10.4)years,including 118 males and 80 females,with a male-to-female ratio of 1.475:1.Compared with the subclinical type,the clinical type had a higher proportion of females,higher levels of serum cortisol,24-hour urine free cortisol(24 h UFC),and inhibited serum cortisol after low-dose dexamethasone suppression.Additionally,the clinical type had lower plasma ACTH,larger adrenal nodules and a higher risk of surgery(P<0.05)compared with those in subclinical type.The incidences of hypertension,dyslipidemia,obesity,diabetes mellitus,hypokalemia,vitamin D deficiency,osteoporosis,coronary heart disease,and cerebrovascular disease in patients with Cushing's syndrome caused by PBMAH were 87.9%,50.5%,37.1%,36.9%,27.8%,25.9%,18.7%,18.7%and 12.1%,respectively.Among them,compared with subclinical type patients,clinical type patients had higher incidence of hypokalaemia,vitamin D deficiency and osteoporosis(P<0.05),while there were no statistically significant differences in the incidences of other comorbidities between the two types(P>0.05).The results of postoperative follow-up for PBMAH patients showed that the short-term biochemical remission rate of unilateral total adrenalectomy was 41.5%(22/53)and the long-term biochemical remission rate was 32.0%(8/25).The short-term biochemical remission rate of unilateral partial(or nodular)adrenalectomy was 52.9%(9/17),and the long-term biochemical remission rate was 14.3%(1/7).All patients who underwent unilateral total adrenalectomy plus contralateral partial resection developed adrenal insufficiency(3/3),and 1 patient(1/3)relapsed 3.4 years after surgery.Conclusion Clinical and subclinical types of Cushing's syndrome caused by PBMAH have their distinct clinical characteristics.Surgery is an effective treatment for PBMAH,but a certain proportion of patients fail to achieve biochemical remission after non-bilateral total adrenalectomy.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

RNA methylation is a key process in the epigenetic regulation of post-transcriptional gene expression.5-Methylcytosine(m⁵C)is a type of RNA methylation,commonly existing in eukaryotic mRNA and non-coding RNAs.It mainly regulates transfer RNA stability,ribosomal RNA assembly,and mRNA translation,stability,and translation.RNA methylation is dynamically reversible and regulated by methyltransferase,demethylase,and methylation recognition protein.It has been confirmed that aberrant m⁵C RNA methylation is involved in the pathogenesis of non-neoplastic kidney diseases.This article summarizes the current progress of m⁵C RNA methylation associated with non-neoplastic acute and chronic kidney diseases,aiming to provide potential targets for the diagnosis and treatment of such diseases.
Humans ; Methylation ; 5-Methylcytosine/metabolism* ; Kidney Diseases/metabolism* ; Epigenesis, Genetic ; RNA Methylation

Objective To explore the effect of management model of clinical pharmacists participating in multidisciplinary collaborative diagnosis and treatment(MDT)for new anti-tumor drugs in the national medical insurance drug negotiation(hereinafter referred to as"national negotiation"),including efficacy,safe-ty,economy and rationality.Methods The medical records of 326 cases using novel anti-tumor drugs by na-tional negotiation and conforming to the including and excluding standards in this hospital from July 2018 to June 2023 were retrospectively analyzed.The patients were divided into the MDT group(n=122)and non-MDT group(n=204).The patients diagnosed as non-small cell lung cancer(NSCLC)in the two groups were extracted and defined as the MDT-NSCLC subgroup(n=41)and non-MDT-NSCLC subgroup(n=77).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR)and the indexes such as survival quality and medical quality control were compared between the groups.Results The median PFS in the two groups was 12.7 months and 8.0 months,the median OS was 75.2 months and 56.3 months,DCR was 96.72％and 81.86％respectively,and the differences were statistically significant(P＜0.05).The COX multivariate regression analysis indicated that the HR value of clinical pharmacists participating in MDT was higher than the other influencing factors.The median PFS time in the MDT-NSCLC subgroup and non-MDT-NSCLC subgroup was 10.5 months and 6.7 months,DCR was 97.30％and 75.64％respectively,and the differences were statistically significant(P＜0.05),the median OS time was 55.1 months and 40.3 months respectively,and the difference was statistically significant(P＞0.05).The COX multivariate regression anal-ysis indicated that the HR value with clinical pharmacists participating in MDT was higher than the other in-fluencing factors;The adverse reaction occurrence rate in the MDT group and non-MDT group was 45.9％and 58.3％respectively,and the difference was statistically significant(P＜0.05).The KPS score after treatment in the MDT group was higher than that in the non-MDT group,and the difference was statistically significant;in the aspect of medical quality control,the average drug proportion in the MDT group and non-MDT group was 63.93％and 64.54％respectively,the rational drug rate of comments on prescription was 98.36％and 88.73％respectively,the patient satisfaction average value was 90.69 points and 87.36 points respectively and the differences were statistically significant(P＜0.05).Conclusion Clinical pharmacists participating in MDT related to novel anti-tumor drugs by national negotiation is beneficial to improve the therapeutic effects,living quality and patient satisfaction,also benefit to management and control of off-label drug use and medical quality control indexes.